Shoulder & Elbow

Platelet-rich plasma (PRP) is a refined product of autologous blood with a platelet concentration greater than that of whole blood. It is prepared via plasmapheresis utilizing a 2-stage centrifugation process and more than 40 commercially available systems are marketed to concentrate whole blood to PRP.¹ It is rich in biologic factors (growth factors, cytokines, proteins, cellular components) essential to the body’s response to injury. For this reason, it was first used in oromaxillofacial surgery in the 1950s, but its effects on the musculoskeletal system have yet to be clearly elucidated.² However, this lack of clarity has not deterred its widespread use among orthopedic surgeons. In this review, we aim to delineate the current understanding of PRP and its proven effectiveness in the treatment of rotator cuff tears, knee osteoarthritis, ulnar collateral ligament (UCL) tears, lateral epicondylitis, hamstring injuries, and Achilles tendinopathy.

Rotator Cuff Tears

Rotator cuff tears are one of the most common etiologies for shoulder pain and disability. The incidence continues to increase with the active aging population.³ Rotator cuff tears treated with arthroscopic repair have exhibited satisfactory pain relief and functional outcomes.^4-7 Despite advances in fixation techniques, the quality and speed of tendon-to-bone healing remains unpredictable, with repaired tendons exhibiting inferior mechanical properties that are susceptible to re-tear.^8-10

Numerous studies have investigated PRP application during arthroscopic rotator cuff repair (RCR) in an attempt to enhance and accelerate the repair process.^11-15 However, wide variability exists among protocols of how and when PRP is utilized to augment the repair. Warth and colleagues¹⁶ performed a meta-analysis of 11 Level I/II studies evaluating RCR with PRP augmentation. With regards to clinical outcome scores, they found no significant difference in pre- and postoperative American Shoulder and Elbow Surgeons (ASES), Constant, Disability of the Arm, Shoulder and Hand (DASH), or visual analog scale (VAS) pain scores between those patients with or without PRP augmentation. However, they did note a significant increase in Constant scores when PRP was delivered to the tendon-bone interface rather than over the surface of the repair site. There was no significant difference in structural outcomes (evaluated by magnetic resonance imaging [MRI] re-tear rates) between those RCRs with and without PRP augmentation, except in those tears >3 cm in anterior-posterior length using double-row technique, with the PRP group exhibiting a significantly decreased re-tear rate (25.9% vs 57.1%).¹⁶ Zhao and colleagues¹⁷ reported similar results in a meta-analysis of 8 randomized controlled trials, exhibiting no significant differences in clinical outcome scores or re-tear rates after RCR with and without PRP augmentation. Overall, most studies have failed to demonstrate a significant benefit with regards to re-tear rates or shoulder-specific outcomes with the addition of PRP during arthroscopic RCR.

Knee Osteoarthritis

Osteoarthritis is the most common musculoskeletal disorder, with an estimated prevalence of 10% of the world’s population age 60 years and older.¹⁸ The knee is commonly symptomatic, resulting in pain, disability, and significant healthcare costs. Novel biologic, nonoperative therapies, including intra-articular viscosupplementation and PRP injections, have been proposed to treat the early stages of osteoarthritis to provide symptomatic relief and delay surgical intervention.

A multitude of studies have been performed investigating the effects of PRP on knee osteoarthritis, revealing mixed results.^19-22 Campbell and colleagues²³ published a 2015 systematic review of 3 overlapping meta-analyses comparing the outcomes of intra-articular injection of PRP vs control (hyaluronic acid [HA] or placebo) in 3278 knees. They reported a significant improvement in patient outcome scores for the PRP group when compared to control from 2 to 12 months after injection, but due to significant differences within the included studies, the ideal number of injections or time intervals between injections remains unclear. Meheux and colleagues²⁴ reported a 2016 systematic review including 6 studies (817 knees) comparing PRP and HA injections. They demonstrated significantly better improvements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) outcome scores with PRP vs HA injections at 3 and 12 months postinjection. Similarly, Smith²⁵ conducted a Food and Drug Administration-sanctioned, randomized, double-blind, placebo-controlled clinical trial investigating the effects of intra-articular leukocyte-poor autologous conditioned plasma (ACP) in 30 patients. He reported an improvement in the ACP treatment group WOMAC scores by 78% compared to 7% improvement in the placebo group after 12 months. Despite the heterogeneity amongst studies, the majority of published data suggests better symptomatic relief in patients with early knee degenerative changes, and use of PRP may be considered in this population.

Ulnar Collateral Ligament Injuries

The anterior band of the UCL of the elbow provides stability to valgus stress. Overhead, high-velocity throwing athletes may cause repetitive injury to the UCL, resulting in partial or complete tears of the ligament. This may result in medial elbow pain, as well as decreased throwing velocity and accuracy. Athletes with complete UCL tears have few nonoperative treatment options and generally, operative treatment with UCL reconstruction is recommended for those athletes desiring to return to sport. However, it remains unclear how to definitively treat athletes with partial UCL tears. Recently, there has been an interest in treating these injuries with PRP in conjunction with physical therapy to facilitate a more predictable outcome.

Podesta and colleagues²⁶ published a case series of 34 athletes with MRI-diagnosed partial UCL tears who underwent ultrasound-guided UCL injections and physical therapy. At an average follow-up of 70 weeks, they reported an average return to play (RTP) of 12 weeks, with significant improvements in Kerlan-Jobe Orthopaedic Clinic (KJOC) and DASH outcome scores, and decreased dynamic ulnohumeral joint widening to valgus stress on ultrasound. Most athletes (30/34) returned to their previous level of play, and 1 patient underwent subsequent UCL reconstruction. This study demonstrates that PRP may be used in conjunction with physical therapy and an interval throwing program for the treatment of partial UCL tears, but without a comparison control group, more studies are necessary to delineate the role of PRP in this population.

Lateral Elbow Epicondylitis

Lateral elbow epicondylitis, also known as “tennis elbow,” is thought to be caused by repetitive wrist extension and is more likely to present in patients with various comorbidities such as rotator cuff pathology or a history of smoking.^27-29 The condition typically presents as radiating pain centered about the lateral epicondyle. Annual incidence ranges from 0.34% to 3%, with the most recent large-scale, population-based study estimating that nearly 1 million individuals in the United States develop lateral elbow epicondylitis each year.³⁰ For the majority of patients, symptoms resolve after 6 to 12 months of various nonoperative or minimally invasive treatments.^31-33 Those who develop chronic symptoms (>12 months) may benefit from surgical intervention.³⁴ The use of PRP has become a contentious topic of debate in treating lateral epicondylitis. Its use and efficacy have been empirically examined and compared among more traditional treatments.^35-37

In a small case-series of 6 patients, contrast-enhanced ultrasound imaging was utilized to demonstrate that PRP injection therapy may induce vascularization of the myotendinous junction of the common extensor tendon up to 6 months following injection.³⁸ These physiologic changes may precede observable clinical improvements. Brklijac and colleagues³⁹ prospectively followed 34 patients who had refractory symptoms despite conservative treatment and elected to undergo injection with PRP. At a mean follow-up of 26 weeks, 88.2% of the patients demonstrated improvements on their Oxford Elbow Score (OES). While potentially promising, case series lack large sample sizes, longitudinal analysis, and adequate control groups for comparative analyses of treatments, thereby increasing the likelihood of unintended selection bias.

Randomized controlled trials have demonstrated no difference between PRP and corticosteroid (CS) injection treatments in the short term for symptomatic lateral elbow epicondylitis. At 15 days, 1 month, and 6 months postinjection, no significant difference was found between PRP and CS injections in dynamometer strength measurements nor patient outcome scores (VAS, DASH, OES, and Mayo Clinic Performance Index for Elbow [MMCPIE]).^40,41 In fact, multiple randomized controlled trials have demonstrated PRP to be less effective at 1 and 3 months compared to CS injections, as assessed by the Patient Rated Tennis-Elbow Evaluation (PRTEE) questionnaire, VAS, MMCPIE, and Nirschl scores.^42,43 One mid-term, multi-center randomized controlled trial published by Mishra and colleagues⁴⁴ compared PRP injections to an active control group, demonstrating a significant improvement in VAS pain scores at 24 weeks, but no difference in the PRTEE outcome. The available evidence indicates PRP injection therapy remains limited in utility for treatment of lateral epicondylitis, particularly in the short term when compared to CS injections. In the midterm to long term, PRP therapy may provide some benefit, but ultimately, well-designed prospective randomized controlled trials are needed to delineate the effects of PRP versus the natural course of tendon healing and symptom resolution.

Hamstring Injuries

Acute hamstring injuries are common across all levels and types of sport, particularly those in which sprinting or running is involved. While there is no consensus within the literature on how RTP after hamstring injury should be managed or defined, most injuries seem to resolve around 3 to 6 weeks.⁴⁵ The proximal myotendinous junction of the long head of the biceps femoris and semitendinosus are commonly associated with significant pain and edema after acute hamstring injury.⁴⁶ The amount of edema resulting from grade 1 and 2 hamstring injuries has been found to correlate (minimally) with time to RTP in elite athletes.⁴⁷ PRP injection near the proximal myotendinous hamstring origin has been theorized to help speed the recovery process after acute hamstring injury. To date, the literature demonstrates mixed and limited benefit of PRP injection therapy for acute hamstring injury.

Few studies have shown improvements of PRP therapy over typical nonoperative management (rest, physical therapy, nonsteroidal anti-inflammatory drugs) in acute hamstring injury, but the results must be interpreted carefully.^48,49 Wetzel and colleagues⁴⁸ retrospectively reviewed 17 patients with acute hamstring injury, 12 of whom failed typical management and received PRP injection at the hamstring origin. This group demonstrated significant improvements in their VAS and Nirschl scores at follow-up, whereas the 5 patients who did not receive the injection did not. However, this study exhibited significant limitations inherent to a retrospective review with a small sample size. Hamid and colleagues⁴⁹ conducted a randomized controlled trial of 24 athletes with diagnosed grade 2a acute hamstring injuries, comparing autologous PRP therapy combined with a rehabilitation program versus rehabilitation program alone. RTP, changes in pain severity (Brief Pain Injury-Short Form [BPI-SF] questions 2-6), and pain interference (BPI-SF questions 9A-9G) scores over time were examined. Athletes in the PRP group exhibited no difference in outcomes scores, but returned to play sooner than controls (26.7 vs 42.5 days).

Mejia and Bradley⁵⁰ have reported their experience in treating 12 National Football League (NFL) players with acute MRI grade 1 or 2 hamstring injuries with a series of PRP injections at the site of injury. They found a 1-game difference in earlier RTP when compared to the predicted RTP based on MRI grading. Similarly, Hamid and colleagues⁴⁹ performed a randomized control trial published in 2014, reporting an earlier RTP (26.7 vs 42.5 days) when comparing single PRP injection vs rehabilitation alone in 28 patients diagnosed with acute ultrasound grade 2 hamstring injuries. On the contrary, a small case-control study of NFL players and a retrospective cohort study of athletes with severe hamstring injuries demonstrated no difference in RTP when PRP injected patients were compared with controls.^51,52 Larger randomized controlled trials have demonstrated comparable results, including a study of 90 professional athletes in whom a single PRP injection did not decrease RTP or lessen the risk of re-injury at 2 and 6 months.⁵³ In another large multicenter randomized controlled trial examining 80 competitive and recreational athletes, PRP did not accelerate RTP, lessen the risk of 2-month or 1-year re-injury rate, or improve secondary measures of MRI parameters, subjective patient satisfaction, or the hamstring outcome score.⁵⁴ Although further study is warranted, available evidence suggests limited utility of PRP injection in the treatment of acute hamstring injuries.

Achilles Tendinopathy

Noninsertional Achilles tendinopathy is a common source of pain for both recreational and competitive athletes. Typically thought of as an overuse syndrome, Achilles tendinopathy may result in significant pain and swelling, often at the site of its tenuous blood supply, approximately 2 to 7 cm proximal to its insertion.⁵⁵ Conservative management frequently begins with rest, activity/shoe modification, physical therapy, and eccentric loading exercises.⁵⁶ For those whom conservative management has failed to reduce symptoms after 6 months, more invasive treatment options may be considered. Peritendinous PRP injection has become an alternative approach in treating Achilles tendinopathy refractory to conservative treatment.

In the few randomized controlled trials published, the data demonstrates no significant improvements in clinical outcomes from PRP injection for Achilles tendinopathy. Kearney and colleagues⁵⁷ conducted a pilot study of 20 patients randomized into PRP injection or eccentric loading program for mid-substance Achilles tendinopathy, in which Victorian Institute of Sports Assessment (VISA-A), EuroQol 5 dimensions questionnaire (EQ-5D), and complications associated with the injection were recorded at 6 weeks, 3 months, and 6 months. Although this was a pilot study with a small sample size, no significant difference was found between groups across these time periods. Similarly, de Vos and colleagues^58,59 conducted a double-blind randomized controlled trial of 54 patients with chronic mid-substance Achilles tendinopathy and randomized them into eccentric exercise therapy with either a PRP injection or a saline injected placebo groups. VISA-A scores were recorded and imaging parameters assessing tendon structure by ultrasonographic tissue characterization and color Doppler ultrasonography were taken with follow-up at 6, 12, and 24 weeks. VISA-A scores improved significantly in both groups after 24 weeks, but the difference was not statistically significant between groups. In addition, tendon structure and neovascularization (exhibited by color Doppler ultrasonography) improved in both groups, with no significant difference between groups. The current literature does not support the use of PRP in treatment of Achilles tendinopathy, as it has failed to reveal additional benefits over conventional treatment alone. Future prospective, well-designed randomized controlled trials with large sample sizes will need to be conducted to ultimately conclude whether or not PRP deserves a role in the treatment of Achilles tendinopathy.

Summary

In theory, the use of PRP within orthopedic surgery makes a great deal of sense to accelerate and augment the healing process of the aforementioned musculoskeletal injuries. However, the vast majority of published literature is Level III and IV evidence. Future research may provide the missing critical information of optimal growth factor, platelet, and leukocyte concentrations necessary for the desired effect, as well as the appropriate delivery method and timing of PRP application in different target tissues. Evidence-based guidelines to direct the use of PRP will benefit from more homogenous, repeatable, and randomized controlled trials.

Platelet-rich plasma (PRP) is a refined product of autologous blood with a platelet concentration greater than that of whole blood. It is prepared via plasmapheresis utilizing a 2-stage centrifugation process and more than 40 commercially available systems are marketed to concentrate whole blood to PRP.¹ It is rich in biologic factors (growth factors, cytokines, proteins, cellular components) essential to the body’s response to injury. For this reason, it was first used in oromaxillofacial surgery in the 1950s, but its effects on the musculoskeletal system have yet to be clearly elucidated.² However, this lack of clarity has not deterred its widespread use among orthopedic surgeons. In this review, we aim to delineate the current understanding of PRP and its proven effectiveness in the treatment of rotator cuff tears, knee osteoarthritis, ulnar collateral ligament (UCL) tears, lateral epicondylitis, hamstring injuries, and Achilles tendinopathy.

Rotator Cuff Tears

Rotator cuff tears are one of the most common etiologies for shoulder pain and disability. The incidence continues to increase with the active aging population.³ Rotator cuff tears treated with arthroscopic repair have exhibited satisfactory pain relief and functional outcomes.^4-7 Despite advances in fixation techniques, the quality and speed of tendon-to-bone healing remains unpredictable, with repaired tendons exhibiting inferior mechanical properties that are susceptible to re-tear.^8-10

Numerous studies have investigated PRP application during arthroscopic rotator cuff repair (RCR) in an attempt to enhance and accelerate the repair process.^11-15 However, wide variability exists among protocols of how and when PRP is utilized to augment the repair. Warth and colleagues¹⁶ performed a meta-analysis of 11 Level I/II studies evaluating RCR with PRP augmentation. With regards to clinical outcome scores, they found no significant difference in pre- and postoperative American Shoulder and Elbow Surgeons (ASES), Constant, Disability of the Arm, Shoulder and Hand (DASH), or visual analog scale (VAS) pain scores between those patients with or without PRP augmentation. However, they did note a significant increase in Constant scores when PRP was delivered to the tendon-bone interface rather than over the surface of the repair site. There was no significant difference in structural outcomes (evaluated by magnetic resonance imaging [MRI] re-tear rates) between those RCRs with and without PRP augmentation, except in those tears >3 cm in anterior-posterior length using double-row technique, with the PRP group exhibiting a significantly decreased re-tear rate (25.9% vs 57.1%).¹⁶ Zhao and colleagues¹⁷ reported similar results in a meta-analysis of 8 randomized controlled trials, exhibiting no significant differences in clinical outcome scores or re-tear rates after RCR with and without PRP augmentation. Overall, most studies have failed to demonstrate a significant benefit with regards to re-tear rates or shoulder-specific outcomes with the addition of PRP during arthroscopic RCR.

Knee Osteoarthritis

Osteoarthritis is the most common musculoskeletal disorder, with an estimated prevalence of 10% of the world’s population age 60 years and older.¹⁸ The knee is commonly symptomatic, resulting in pain, disability, and significant healthcare costs. Novel biologic, nonoperative therapies, including intra-articular viscosupplementation and PRP injections, have been proposed to treat the early stages of osteoarthritis to provide symptomatic relief and delay surgical intervention.

A multitude of studies have been performed investigating the effects of PRP on knee osteoarthritis, revealing mixed results.^19-22 Campbell and colleagues²³ published a 2015 systematic review of 3 overlapping meta-analyses comparing the outcomes of intra-articular injection of PRP vs control (hyaluronic acid [HA] or placebo) in 3278 knees. They reported a significant improvement in patient outcome scores for the PRP group when compared to control from 2 to 12 months after injection, but due to significant differences within the included studies, the ideal number of injections or time intervals between injections remains unclear. Meheux and colleagues²⁴ reported a 2016 systematic review including 6 studies (817 knees) comparing PRP and HA injections. They demonstrated significantly better improvements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) outcome scores with PRP vs HA injections at 3 and 12 months postinjection. Similarly, Smith²⁵ conducted a Food and Drug Administration-sanctioned, randomized, double-blind, placebo-controlled clinical trial investigating the effects of intra-articular leukocyte-poor autologous conditioned plasma (ACP) in 30 patients. He reported an improvement in the ACP treatment group WOMAC scores by 78% compared to 7% improvement in the placebo group after 12 months. Despite the heterogeneity amongst studies, the majority of published data suggests better symptomatic relief in patients with early knee degenerative changes, and use of PRP may be considered in this population.

Ulnar Collateral Ligament Injuries

The anterior band of the UCL of the elbow provides stability to valgus stress. Overhead, high-velocity throwing athletes may cause repetitive injury to the UCL, resulting in partial or complete tears of the ligament. This may result in medial elbow pain, as well as decreased throwing velocity and accuracy. Athletes with complete UCL tears have few nonoperative treatment options and generally, operative treatment with UCL reconstruction is recommended for those athletes desiring to return to sport. However, it remains unclear how to definitively treat athletes with partial UCL tears. Recently, there has been an interest in treating these injuries with PRP in conjunction with physical therapy to facilitate a more predictable outcome.

Podesta and colleagues²⁶ published a case series of 34 athletes with MRI-diagnosed partial UCL tears who underwent ultrasound-guided UCL injections and physical therapy. At an average follow-up of 70 weeks, they reported an average return to play (RTP) of 12 weeks, with significant improvements in Kerlan-Jobe Orthopaedic Clinic (KJOC) and DASH outcome scores, and decreased dynamic ulnohumeral joint widening to valgus stress on ultrasound. Most athletes (30/34) returned to their previous level of play, and 1 patient underwent subsequent UCL reconstruction. This study demonstrates that PRP may be used in conjunction with physical therapy and an interval throwing program for the treatment of partial UCL tears, but without a comparison control group, more studies are necessary to delineate the role of PRP in this population.

Lateral Elbow Epicondylitis

Lateral elbow epicondylitis, also known as “tennis elbow,” is thought to be caused by repetitive wrist extension and is more likely to present in patients with various comorbidities such as rotator cuff pathology or a history of smoking.^27-29 The condition typically presents as radiating pain centered about the lateral epicondyle. Annual incidence ranges from 0.34% to 3%, with the most recent large-scale, population-based study estimating that nearly 1 million individuals in the United States develop lateral elbow epicondylitis each year.³⁰ For the majority of patients, symptoms resolve after 6 to 12 months of various nonoperative or minimally invasive treatments.^31-33 Those who develop chronic symptoms (>12 months) may benefit from surgical intervention.³⁴ The use of PRP has become a contentious topic of debate in treating lateral epicondylitis. Its use and efficacy have been empirically examined and compared among more traditional treatments.^35-37

In a small case-series of 6 patients, contrast-enhanced ultrasound imaging was utilized to demonstrate that PRP injection therapy may induce vascularization of the myotendinous junction of the common extensor tendon up to 6 months following injection.³⁸ These physiologic changes may precede observable clinical improvements. Brklijac and colleagues³⁹ prospectively followed 34 patients who had refractory symptoms despite conservative treatment and elected to undergo injection with PRP. At a mean follow-up of 26 weeks, 88.2% of the patients demonstrated improvements on their Oxford Elbow Score (OES). While potentially promising, case series lack large sample sizes, longitudinal analysis, and adequate control groups for comparative analyses of treatments, thereby increasing the likelihood of unintended selection bias.

Randomized controlled trials have demonstrated no difference between PRP and corticosteroid (CS) injection treatments in the short term for symptomatic lateral elbow epicondylitis. At 15 days, 1 month, and 6 months postinjection, no significant difference was found between PRP and CS injections in dynamometer strength measurements nor patient outcome scores (VAS, DASH, OES, and Mayo Clinic Performance Index for Elbow [MMCPIE]).^40,41 In fact, multiple randomized controlled trials have demonstrated PRP to be less effective at 1 and 3 months compared to CS injections, as assessed by the Patient Rated Tennis-Elbow Evaluation (PRTEE) questionnaire, VAS, MMCPIE, and Nirschl scores.^42,43 One mid-term, multi-center randomized controlled trial published by Mishra and colleagues⁴⁴ compared PRP injections to an active control group, demonstrating a significant improvement in VAS pain scores at 24 weeks, but no difference in the PRTEE outcome. The available evidence indicates PRP injection therapy remains limited in utility for treatment of lateral epicondylitis, particularly in the short term when compared to CS injections. In the midterm to long term, PRP therapy may provide some benefit, but ultimately, well-designed prospective randomized controlled trials are needed to delineate the effects of PRP versus the natural course of tendon healing and symptom resolution.

Hamstring Injuries

Acute hamstring injuries are common across all levels and types of sport, particularly those in which sprinting or running is involved. While there is no consensus within the literature on how RTP after hamstring injury should be managed or defined, most injuries seem to resolve around 3 to 6 weeks.⁴⁵ The proximal myotendinous junction of the long head of the biceps femoris and semitendinosus are commonly associated with significant pain and edema after acute hamstring injury.⁴⁶ The amount of edema resulting from grade 1 and 2 hamstring injuries has been found to correlate (minimally) with time to RTP in elite athletes.⁴⁷ PRP injection near the proximal myotendinous hamstring origin has been theorized to help speed the recovery process after acute hamstring injury. To date, the literature demonstrates mixed and limited benefit of PRP injection therapy for acute hamstring injury.

Few studies have shown improvements of PRP therapy over typical nonoperative management (rest, physical therapy, nonsteroidal anti-inflammatory drugs) in acute hamstring injury, but the results must be interpreted carefully.^48,49 Wetzel and colleagues⁴⁸ retrospectively reviewed 17 patients with acute hamstring injury, 12 of whom failed typical management and received PRP injection at the hamstring origin. This group demonstrated significant improvements in their VAS and Nirschl scores at follow-up, whereas the 5 patients who did not receive the injection did not. However, this study exhibited significant limitations inherent to a retrospective review with a small sample size. Hamid and colleagues⁴⁹ conducted a randomized controlled trial of 24 athletes with diagnosed grade 2a acute hamstring injuries, comparing autologous PRP therapy combined with a rehabilitation program versus rehabilitation program alone. RTP, changes in pain severity (Brief Pain Injury-Short Form [BPI-SF] questions 2-6), and pain interference (BPI-SF questions 9A-9G) scores over time were examined. Athletes in the PRP group exhibited no difference in outcomes scores, but returned to play sooner than controls (26.7 vs 42.5 days).

Mejia and Bradley⁵⁰ have reported their experience in treating 12 National Football League (NFL) players with acute MRI grade 1 or 2 hamstring injuries with a series of PRP injections at the site of injury. They found a 1-game difference in earlier RTP when compared to the predicted RTP based on MRI grading. Similarly, Hamid and colleagues⁴⁹ performed a randomized control trial published in 2014, reporting an earlier RTP (26.7 vs 42.5 days) when comparing single PRP injection vs rehabilitation alone in 28 patients diagnosed with acute ultrasound grade 2 hamstring injuries. On the contrary, a small case-control study of NFL players and a retrospective cohort study of athletes with severe hamstring injuries demonstrated no difference in RTP when PRP injected patients were compared with controls.^51,52 Larger randomized controlled trials have demonstrated comparable results, including a study of 90 professional athletes in whom a single PRP injection did not decrease RTP or lessen the risk of re-injury at 2 and 6 months.⁵³ In another large multicenter randomized controlled trial examining 80 competitive and recreational athletes, PRP did not accelerate RTP, lessen the risk of 2-month or 1-year re-injury rate, or improve secondary measures of MRI parameters, subjective patient satisfaction, or the hamstring outcome score.⁵⁴ Although further study is warranted, available evidence suggests limited utility of PRP injection in the treatment of acute hamstring injuries.

Achilles Tendinopathy

Noninsertional Achilles tendinopathy is a common source of pain for both recreational and competitive athletes. Typically thought of as an overuse syndrome, Achilles tendinopathy may result in significant pain and swelling, often at the site of its tenuous blood supply, approximately 2 to 7 cm proximal to its insertion.⁵⁵ Conservative management frequently begins with rest, activity/shoe modification, physical therapy, and eccentric loading exercises.⁵⁶ For those whom conservative management has failed to reduce symptoms after 6 months, more invasive treatment options may be considered. Peritendinous PRP injection has become an alternative approach in treating Achilles tendinopathy refractory to conservative treatment.

In the few randomized controlled trials published, the data demonstrates no significant improvements in clinical outcomes from PRP injection for Achilles tendinopathy. Kearney and colleagues⁵⁷ conducted a pilot study of 20 patients randomized into PRP injection or eccentric loading program for mid-substance Achilles tendinopathy, in which Victorian Institute of Sports Assessment (VISA-A), EuroQol 5 dimensions questionnaire (EQ-5D), and complications associated with the injection were recorded at 6 weeks, 3 months, and 6 months. Although this was a pilot study with a small sample size, no significant difference was found between groups across these time periods. Similarly, de Vos and colleagues^58,59 conducted a double-blind randomized controlled trial of 54 patients with chronic mid-substance Achilles tendinopathy and randomized them into eccentric exercise therapy with either a PRP injection or a saline injected placebo groups. VISA-A scores were recorded and imaging parameters assessing tendon structure by ultrasonographic tissue characterization and color Doppler ultrasonography were taken with follow-up at 6, 12, and 24 weeks. VISA-A scores improved significantly in both groups after 24 weeks, but the difference was not statistically significant between groups. In addition, tendon structure and neovascularization (exhibited by color Doppler ultrasonography) improved in both groups, with no significant difference between groups. The current literature does not support the use of PRP in treatment of Achilles tendinopathy, as it has failed to reveal additional benefits over conventional treatment alone. Future prospective, well-designed randomized controlled trials with large sample sizes will need to be conducted to ultimately conclude whether or not PRP deserves a role in the treatment of Achilles tendinopathy.

Summary

In theory, the use of PRP within orthopedic surgery makes a great deal of sense to accelerate and augment the healing process of the aforementioned musculoskeletal injuries. However, the vast majority of published literature is Level III and IV evidence. Future research may provide the missing critical information of optimal growth factor, platelet, and leukocyte concentrations necessary for the desired effect, as well as the appropriate delivery method and timing of PRP application in different target tissues. Evidence-based guidelines to direct the use of PRP will benefit from more homogenous, repeatable, and randomized controlled trials.

Platelet-rich plasma (PRP) is a refined product of autologous blood with a platelet concentration greater than that of whole blood. It is prepared via plasmapheresis utilizing a 2-stage centrifugation process and more than 40 commercially available systems are marketed to concentrate whole blood to PRP.¹ It is rich in biologic factors (growth factors, cytokines, proteins, cellular components) essential to the body’s response to injury. For this reason, it was first used in oromaxillofacial surgery in the 1950s, but its effects on the musculoskeletal system have yet to be clearly elucidated.² However, this lack of clarity has not deterred its widespread use among orthopedic surgeons. In this review, we aim to delineate the current understanding of PRP and its proven effectiveness in the treatment of rotator cuff tears, knee osteoarthritis, ulnar collateral ligament (UCL) tears, lateral epicondylitis, hamstring injuries, and Achilles tendinopathy.

Rotator Cuff Tears

Rotator cuff tears are one of the most common etiologies for shoulder pain and disability. The incidence continues to increase with the active aging population.³ Rotator cuff tears treated with arthroscopic repair have exhibited satisfactory pain relief and functional outcomes.^4-7 Despite advances in fixation techniques, the quality and speed of tendon-to-bone healing remains unpredictable, with repaired tendons exhibiting inferior mechanical properties that are susceptible to re-tear.^8-10

Numerous studies have investigated PRP application during arthroscopic rotator cuff repair (RCR) in an attempt to enhance and accelerate the repair process.^11-15 However, wide variability exists among protocols of how and when PRP is utilized to augment the repair. Warth and colleagues¹⁶ performed a meta-analysis of 11 Level I/II studies evaluating RCR with PRP augmentation. With regards to clinical outcome scores, they found no significant difference in pre- and postoperative American Shoulder and Elbow Surgeons (ASES), Constant, Disability of the Arm, Shoulder and Hand (DASH), or visual analog scale (VAS) pain scores between those patients with or without PRP augmentation. However, they did note a significant increase in Constant scores when PRP was delivered to the tendon-bone interface rather than over the surface of the repair site. There was no significant difference in structural outcomes (evaluated by magnetic resonance imaging [MRI] re-tear rates) between those RCRs with and without PRP augmentation, except in those tears >3 cm in anterior-posterior length using double-row technique, with the PRP group exhibiting a significantly decreased re-tear rate (25.9% vs 57.1%).¹⁶ Zhao and colleagues¹⁷ reported similar results in a meta-analysis of 8 randomized controlled trials, exhibiting no significant differences in clinical outcome scores or re-tear rates after RCR with and without PRP augmentation. Overall, most studies have failed to demonstrate a significant benefit with regards to re-tear rates or shoulder-specific outcomes with the addition of PRP during arthroscopic RCR.

Knee Osteoarthritis

Osteoarthritis is the most common musculoskeletal disorder, with an estimated prevalence of 10% of the world’s population age 60 years and older.¹⁸ The knee is commonly symptomatic, resulting in pain, disability, and significant healthcare costs. Novel biologic, nonoperative therapies, including intra-articular viscosupplementation and PRP injections, have been proposed to treat the early stages of osteoarthritis to provide symptomatic relief and delay surgical intervention.

A multitude of studies have been performed investigating the effects of PRP on knee osteoarthritis, revealing mixed results.^19-22 Campbell and colleagues²³ published a 2015 systematic review of 3 overlapping meta-analyses comparing the outcomes of intra-articular injection of PRP vs control (hyaluronic acid [HA] or placebo) in 3278 knees. They reported a significant improvement in patient outcome scores for the PRP group when compared to control from 2 to 12 months after injection, but due to significant differences within the included studies, the ideal number of injections or time intervals between injections remains unclear. Meheux and colleagues²⁴ reported a 2016 systematic review including 6 studies (817 knees) comparing PRP and HA injections. They demonstrated significantly better improvements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) outcome scores with PRP vs HA injections at 3 and 12 months postinjection. Similarly, Smith²⁵ conducted a Food and Drug Administration-sanctioned, randomized, double-blind, placebo-controlled clinical trial investigating the effects of intra-articular leukocyte-poor autologous conditioned plasma (ACP) in 30 patients. He reported an improvement in the ACP treatment group WOMAC scores by 78% compared to 7% improvement in the placebo group after 12 months. Despite the heterogeneity amongst studies, the majority of published data suggests better symptomatic relief in patients with early knee degenerative changes, and use of PRP may be considered in this population.

Ulnar Collateral Ligament Injuries

The anterior band of the UCL of the elbow provides stability to valgus stress. Overhead, high-velocity throwing athletes may cause repetitive injury to the UCL, resulting in partial or complete tears of the ligament. This may result in medial elbow pain, as well as decreased throwing velocity and accuracy. Athletes with complete UCL tears have few nonoperative treatment options and generally, operative treatment with UCL reconstruction is recommended for those athletes desiring to return to sport. However, it remains unclear how to definitively treat athletes with partial UCL tears. Recently, there has been an interest in treating these injuries with PRP in conjunction with physical therapy to facilitate a more predictable outcome.

Podesta and colleagues²⁶ published a case series of 34 athletes with MRI-diagnosed partial UCL tears who underwent ultrasound-guided UCL injections and physical therapy. At an average follow-up of 70 weeks, they reported an average return to play (RTP) of 12 weeks, with significant improvements in Kerlan-Jobe Orthopaedic Clinic (KJOC) and DASH outcome scores, and decreased dynamic ulnohumeral joint widening to valgus stress on ultrasound. Most athletes (30/34) returned to their previous level of play, and 1 patient underwent subsequent UCL reconstruction. This study demonstrates that PRP may be used in conjunction with physical therapy and an interval throwing program for the treatment of partial UCL tears, but without a comparison control group, more studies are necessary to delineate the role of PRP in this population.

Lateral Elbow Epicondylitis

Lateral elbow epicondylitis, also known as “tennis elbow,” is thought to be caused by repetitive wrist extension and is more likely to present in patients with various comorbidities such as rotator cuff pathology or a history of smoking.^27-29 The condition typically presents as radiating pain centered about the lateral epicondyle. Annual incidence ranges from 0.34% to 3%, with the most recent large-scale, population-based study estimating that nearly 1 million individuals in the United States develop lateral elbow epicondylitis each year.³⁰ For the majority of patients, symptoms resolve after 6 to 12 months of various nonoperative or minimally invasive treatments.^31-33 Those who develop chronic symptoms (>12 months) may benefit from surgical intervention.³⁴ The use of PRP has become a contentious topic of debate in treating lateral epicondylitis. Its use and efficacy have been empirically examined and compared among more traditional treatments.^35-37

In a small case-series of 6 patients, contrast-enhanced ultrasound imaging was utilized to demonstrate that PRP injection therapy may induce vascularization of the myotendinous junction of the common extensor tendon up to 6 months following injection.³⁸ These physiologic changes may precede observable clinical improvements. Brklijac and colleagues³⁹ prospectively followed 34 patients who had refractory symptoms despite conservative treatment and elected to undergo injection with PRP. At a mean follow-up of 26 weeks, 88.2% of the patients demonstrated improvements on their Oxford Elbow Score (OES). While potentially promising, case series lack large sample sizes, longitudinal analysis, and adequate control groups for comparative analyses of treatments, thereby increasing the likelihood of unintended selection bias.

Randomized controlled trials have demonstrated no difference between PRP and corticosteroid (CS) injection treatments in the short term for symptomatic lateral elbow epicondylitis. At 15 days, 1 month, and 6 months postinjection, no significant difference was found between PRP and CS injections in dynamometer strength measurements nor patient outcome scores (VAS, DASH, OES, and Mayo Clinic Performance Index for Elbow [MMCPIE]).^40,41 In fact, multiple randomized controlled trials have demonstrated PRP to be less effective at 1 and 3 months compared to CS injections, as assessed by the Patient Rated Tennis-Elbow Evaluation (PRTEE) questionnaire, VAS, MMCPIE, and Nirschl scores.^42,43 One mid-term, multi-center randomized controlled trial published by Mishra and colleagues⁴⁴ compared PRP injections to an active control group, demonstrating a significant improvement in VAS pain scores at 24 weeks, but no difference in the PRTEE outcome. The available evidence indicates PRP injection therapy remains limited in utility for treatment of lateral epicondylitis, particularly in the short term when compared to CS injections. In the midterm to long term, PRP therapy may provide some benefit, but ultimately, well-designed prospective randomized controlled trials are needed to delineate the effects of PRP versus the natural course of tendon healing and symptom resolution.

Hamstring Injuries

Acute hamstring injuries are common across all levels and types of sport, particularly those in which sprinting or running is involved. While there is no consensus within the literature on how RTP after hamstring injury should be managed or defined, most injuries seem to resolve around 3 to 6 weeks.⁴⁵ The proximal myotendinous junction of the long head of the biceps femoris and semitendinosus are commonly associated with significant pain and edema after acute hamstring injury.⁴⁶ The amount of edema resulting from grade 1 and 2 hamstring injuries has been found to correlate (minimally) with time to RTP in elite athletes.⁴⁷ PRP injection near the proximal myotendinous hamstring origin has been theorized to help speed the recovery process after acute hamstring injury. To date, the literature demonstrates mixed and limited benefit of PRP injection therapy for acute hamstring injury.

Few studies have shown improvements of PRP therapy over typical nonoperative management (rest, physical therapy, nonsteroidal anti-inflammatory drugs) in acute hamstring injury, but the results must be interpreted carefully.^48,49 Wetzel and colleagues⁴⁸ retrospectively reviewed 17 patients with acute hamstring injury, 12 of whom failed typical management and received PRP injection at the hamstring origin. This group demonstrated significant improvements in their VAS and Nirschl scores at follow-up, whereas the 5 patients who did not receive the injection did not. However, this study exhibited significant limitations inherent to a retrospective review with a small sample size. Hamid and colleagues⁴⁹ conducted a randomized controlled trial of 24 athletes with diagnosed grade 2a acute hamstring injuries, comparing autologous PRP therapy combined with a rehabilitation program versus rehabilitation program alone. RTP, changes in pain severity (Brief Pain Injury-Short Form [BPI-SF] questions 2-6), and pain interference (BPI-SF questions 9A-9G) scores over time were examined. Athletes in the PRP group exhibited no difference in outcomes scores, but returned to play sooner than controls (26.7 vs 42.5 days).

Mejia and Bradley⁵⁰ have reported their experience in treating 12 National Football League (NFL) players with acute MRI grade 1 or 2 hamstring injuries with a series of PRP injections at the site of injury. They found a 1-game difference in earlier RTP when compared to the predicted RTP based on MRI grading. Similarly, Hamid and colleagues⁴⁹ performed a randomized control trial published in 2014, reporting an earlier RTP (26.7 vs 42.5 days) when comparing single PRP injection vs rehabilitation alone in 28 patients diagnosed with acute ultrasound grade 2 hamstring injuries. On the contrary, a small case-control study of NFL players and a retrospective cohort study of athletes with severe hamstring injuries demonstrated no difference in RTP when PRP injected patients were compared with controls.^51,52 Larger randomized controlled trials have demonstrated comparable results, including a study of 90 professional athletes in whom a single PRP injection did not decrease RTP or lessen the risk of re-injury at 2 and 6 months.⁵³ In another large multicenter randomized controlled trial examining 80 competitive and recreational athletes, PRP did not accelerate RTP, lessen the risk of 2-month or 1-year re-injury rate, or improve secondary measures of MRI parameters, subjective patient satisfaction, or the hamstring outcome score.⁵⁴ Although further study is warranted, available evidence suggests limited utility of PRP injection in the treatment of acute hamstring injuries.

Achilles Tendinopathy

Noninsertional Achilles tendinopathy is a common source of pain for both recreational and competitive athletes. Typically thought of as an overuse syndrome, Achilles tendinopathy may result in significant pain and swelling, often at the site of its tenuous blood supply, approximately 2 to 7 cm proximal to its insertion.⁵⁵ Conservative management frequently begins with rest, activity/shoe modification, physical therapy, and eccentric loading exercises.⁵⁶ For those whom conservative management has failed to reduce symptoms after 6 months, more invasive treatment options may be considered. Peritendinous PRP injection has become an alternative approach in treating Achilles tendinopathy refractory to conservative treatment.

In the few randomized controlled trials published, the data demonstrates no significant improvements in clinical outcomes from PRP injection for Achilles tendinopathy. Kearney and colleagues⁵⁷ conducted a pilot study of 20 patients randomized into PRP injection or eccentric loading program for mid-substance Achilles tendinopathy, in which Victorian Institute of Sports Assessment (VISA-A), EuroQol 5 dimensions questionnaire (EQ-5D), and complications associated with the injection were recorded at 6 weeks, 3 months, and 6 months. Although this was a pilot study with a small sample size, no significant difference was found between groups across these time periods. Similarly, de Vos and colleagues^58,59 conducted a double-blind randomized controlled trial of 54 patients with chronic mid-substance Achilles tendinopathy and randomized them into eccentric exercise therapy with either a PRP injection or a saline injected placebo groups. VISA-A scores were recorded and imaging parameters assessing tendon structure by ultrasonographic tissue characterization and color Doppler ultrasonography were taken with follow-up at 6, 12, and 24 weeks. VISA-A scores improved significantly in both groups after 24 weeks, but the difference was not statistically significant between groups. In addition, tendon structure and neovascularization (exhibited by color Doppler ultrasonography) improved in both groups, with no significant difference between groups. The current literature does not support the use of PRP in treatment of Achilles tendinopathy, as it has failed to reveal additional benefits over conventional treatment alone. Future prospective, well-designed randomized controlled trials with large sample sizes will need to be conducted to ultimately conclude whether or not PRP deserves a role in the treatment of Achilles tendinopathy.

Summary

In theory, the use of PRP within orthopedic surgery makes a great deal of sense to accelerate and augment the healing process of the aforementioned musculoskeletal injuries. However, the vast majority of published literature is Level III and IV evidence. Future research may provide the missing critical information of optimal growth factor, platelet, and leukocyte concentrations necessary for the desired effect, as well as the appropriate delivery method and timing of PRP application in different target tissues. Evidence-based guidelines to direct the use of PRP will benefit from more homogenous, repeatable, and randomized controlled trials.

Biologic use in orthopedics is a continuously evolving field that complements technical, anatomic, and biomechanical advancements in orthopedics. Biologic agents are receiving increasing attention for their use in augmenting healing of muscles, tendons, ligaments, and osseous structures. As biologic augmentation strategies become increasingly utilized in bony and soft-tissue injuries, research on stem cell use in orthopedics continues to increase. Stem cell-based therapies for the repair or regeneration of muscle and tendon represent a promising technology going forward for numerous diseases.¹

Stem cells by definition are undifferentiated cells that have 4 main characteristics: (1) mobilization during angiogenesis, (2) differentiation into specialized cell types, (3) proliferation and regeneration, and (4) release of immune regulators and growth factors.² Mesenchymal stem cells (MSCs) have garnered the most attention in the field of surgery due to their ability to differentiate into the tissues of interest for the surgeon.³ This includes both bone marrow-derived mesenchymal stem cells (bm-MSCs) and adipose-derived mesenchymal stem cells (a-MSCs). These multipotent stem cells in adults originate from mesenchymal tissues, including bone marrow, tendon, adipose, and muscle tissue.⁴ They are attractive for clinical use because of their multipotent potential and relative ease of growth in culture.⁵ They also exert a paracrine effect to modulate and control inflammation, stimulate endogenous cell repair and proliferation, inhibit apoptosis, and improve blood flow through secretion of chemokines, cytokines, and growth factors.^6,7

Questions exist regarding the best way to administer stem cells, whether systematic administration is possible for these cells to localize to the tissue in need, or more likely if direct application to the pathologic area is necessary.^8,9 A number of sources, purification process, and modes of delivery are available, but the most effective means of preparation and administration are still under investigation. The goal of this review is to illustrate the current state of knowledge surrounding stem cell therapy in orthopedics with a focus on osteoarthritis, tendinopathy, articular cartilage, and enhancement of surgical procedures.

Important Considerations

Common stem cell isolates include embryonic, induced pluripotent, and mesenchymal formulations (Table 1). MSCs can be obtained from multiple sites, including but not limited to the adult bone marrow, adipose, muscular, or tendinous tissues, and their use has been highlighted in the study of numerous orthopedic and nonorthopedic pathologies over the course of the last decade. Research on the use of embryonic stem cells in medical therapy with human implications has received substantial attention, with many ethical concerns by those opposed, and the existence of a potential risk of malignant alterations.^8,10 Amniotic-derived stem cells can be isolated from amniotic fluid, umbilical cord blood, or the placenta and thus do not harbor the same social constraints as the aforementioned embryonic cells; however, they do not harbor the same magnitude of multi-differentiation potential, either.⁴

Adult MSCs are more locally available and easy to obtain for treatment when compared with embryonic and fetal stem cells, and the former has a lower immunogenicity, which allows allogeneic use.¹¹ Safety has been preliminarily demonstrated in use thus far; Centeno and colleagues¹² found no neoplastic tissue generation at the site of stem cell injection after 3 years postinjection for a cohort of patients who were treated with autologous bm-MSCs for various pathologies. Self-limited pain and swelling are the most commonly reported adverse events after use.¹³ However, long-term data are lacking in many instances to definitively suggest the absence of possible complications.

Basic Science

Stem cell research encompasses a wide range of rapidly developing treatment strategies that are applicable to virtually every field of medicine. In general, stem cells can be classified as embryonic stem cells (ESCs), induced pluripotent stem (iPS) cells, or adult-derived MSCs. ESCs are embryonic cells derived typically from fetal tissue, whereas iPS cells are dedifferentiated from adult tissue, thus avoiding many of the ethical and legal challenges imposed by research with ESCs. However, oncogenic and lingering politico-legal concerns with introducing dedifferentiated ESCs or iPS cells into healthy tissue necessitate the development, isolation, and expansion of multi- but not pluripotent stem cell lines.¹⁴ To date, the most advantageous and widely utilized from any perspective are MSCs, which can further differentiate into cartilage, tendon, muscle, and bony tissue.^7,15,16

MSCs are defined by their ability to demonstrate in vitro differentiation into osteoblasts, adipocytes, or chondroblasts, adhere to plastic, express CD105, CD73, and CD90, and not express CD43, CD23, CD14 or CD11b, CD79 or CD19, or HLA-DR.¹⁷ Porada and Almeida-Porada¹⁸ have outlined 6 reasons highlighting the advantages of MSCs: 1) ease of isolation, 2) high differentiation capabilities, 3) strong colony expansion without differentiation loss, 4) immunosuppression following transplantation, 5) powerful anti-inflammatory properties, and 6) their ability to localize to damaged tissue. The anti-inflammatory properties of MSCs are particularly important as they promote allo- and xenotransplantation from donor tissues.^19,20 MSCs can be isolated from numerous sources, including but not limited to bone marrow, periosteum, adipocyte, and muscle.^21-23 Interestingly, the source tissue used to isolate MSCs can affect differentiation capabilities, colony size, and growth rate (Table 2).²⁴ Advantages of a-MSCs include high prevalence and ease of harvest; however, several animal studies have shown inferior results when compared to bm-MSCs.^25-27 More research is needed to determine the ideal source material for MSCs, which will likely depend in part on the procedure for which they are employed.²⁷

Following harvesting, isolation, and expansion, MSC delivery methods for treatments typically consist of either cell-based or tissue engineering approaches. Cell-based techniques involve the injection of MSCs into damaged tissues. Purely cell-based therapy has shown success in limited clinical trials involving knee osteoarthritis, cartilage repair, and meniscal repair.^28-30 However, additional studies with longer follow-up are required to validate these preliminary findings. Tissue engineering approaches involve the construction of a 3-dimensional scaffold seeded with MSCs that is later surgically implanted. While promising in theory, limited and often conflicting data exist regarding the efficacy of tissue-engineered MSC implantation.^31-32 Suboptimal scaffold vascularity is a major limitation to scaffold design, which may be alleviated in part with the advent of 3-dimensional printing and the ability to more precisely alter scaffold architecture.^14,33 Additional limitations include ensuring MSC purity and differentiation potential following harvesting and expansion. At present, the use of tissue engineering with MSCs is promising but it remains a nascent technology with additional preclinical studies required to confirm implant efficacy and safety.

Clinical Entities

Osteoarthritis

MSC therapies have emerged as promising treatment strategies in the setting of early osteoarthritis (OA). In addition to their regenerative potential, MSCs demonstrate potent anti-inflammatory properties, increasing their attractiveness as biologic agents in the setting of OA.³⁴ Over the past decade, multiple human trials have been published demonstrating the efficacy of MSC injections into patients with OA.^35,36 In a study evaluating a-MSC injection into elderly patients (age >65 years) with knee OA, Koh and colleagues²⁹ found that 88% demonstrated improved cartilage status at 2-year follow-up, while no patient underwent a total knee arthroplasty during this time period. In another study investigating patients with unicompartmental knee OA with varus alignment undergoing high tibial osteotomy and microfracture, Wong and colleagues³⁷ reported improved clinical, patient-reported, and magnetic resonance imaging (MRI)-based outcomes in a group receiving a preoperative MSC injection compared to a control group. Further, in a recent randomized control trial of patients with knee osteoarthritis, Vega and colleagues³⁸ reported improved cartilage and quality of life outcomes at 1 year following MSC injection compared to a control group receiving a hyaluronic acid injection. In addition to knee OA, studies have also reported improvement in ankle OA following MSC injection.³⁹ While promising, many of the preliminary clinical studies evaluating the efficacy of MSC therapies in the treatment of OA are hindered by small patient populations and short-term follow-up. Additional large-scale, randomized studies are required and many are ongoing presently in hopes of validating these preliminary findings.³⁶

Tendinopathy

The quality of repaired tissue in primary tendon-to-tendon and tendon-to-bone healing has long been a topic of great interest.⁴⁰ The healing potential of tendons is inferior to that of other bony and connective tissues,⁴¹ with tendon healing typically resulting in a biomechanically and histologically inferior structure to the native tissue.⁴² As such, this has been a particularly salient opportunity for stem cell use with hopes of recapitulating a more normal tendon or tendon enthesis following injury. In addition to the acute injury, there is great interest in the application of stem cells to chronic states of injury such as tendinopathy.

In equine models, the effect of autologous bm-MSCs treatment on tendinopathy of the superficial digital flexor tendon has been studied. Godwin and colleagues⁴³ evaluated 141 race horses with spontaneous superficial digital flexor tendinopathy treated in this manner, and reported a reinjury percentage in these treated horses of just 27.4%, which compared favorably to historical controls and alternative therapeutics. Machova Urdzikova and colleagues⁴⁴ injected MSCs at Achilles tendinopathy locations to augment nonoperative healing in 40 rats, and identified more native histological organization and improved vascularization in comparison to control rat specimens. Oshita and colleagues⁴⁵ reported histologic improvement of tendinopathy findings in 8 rats receiving a-MSCs at the location of induced Achilles tendinopathy that was significantly superior to a control cohort. Bm-MSCs were used by Yuksel and colleagues⁴⁶ in comparison with platelet-rich plasma (PRP) for treatment of Achilles tendon ruptures created surgically in rat models. They demonstrated successful effects with its use in terms of recovery for the tendon’s histopathologic, immunohistochemical, and biomechanical properties, related to significantly greater levels of anti-inflammatory cytokines. However, these aforementioned findings have not been uniform across the literature—other authors have reported findings that MSC transplantation alone did not repair Achilles tendon injury with such high levels of success.⁴⁷

Human treatment of tendinopathies with stem cells has been scarcely studied to date. Pascual-Garrido and colleagues⁴⁸ evaluated 8 patients with refractory patellar tendinopathy treated with injection of autologous bm-MSCs and reported successful results at 2- to 5-year follow-up, with significant improvements in patient-reported outcome measures for 100% of patients. Seven of 8 (87.5%) noted that they would undergo the procedure again.

Articular Cartilage Injury

Chondral injury is a particularly important subject given the limited potential of chondrocytes to replicate or migrate to the site of pathology.⁴⁹ Stem cell use in this setting assists with programmed growth factor release and alteration of the anatomic microenvironment to facilitate regeneration and repair of the chondral surface. Autologous stem cell use through microfracture provides a perforation into the bone marrow and a subsequent fibrin clot formation containing platelets, growth factors, vascular elements, and MSCs.⁵⁰ A similar concept to PRP is currently being explored with bm-MSCs. Isolated bm-MSCs are commonly referred to as bone marrow aspirate or bone marrow aspirate concentrate (BMAC). Commercially available systems are now available to aid in the harvesting and implementation of BMAC. One of the more promising avenues for BMAC implementation is in articular cartilage repair or regeneration due to chondrogenic potential of BMAC when used in isolation or when combined with microfracture, chondrocyte transfer, or collagen scaffolds.^19,51 Synovial-derived stem cells as an additional source for stem cell use has demonstrated excellent chondrogenic potential in animal studies with full-thickness lesion healing and native-appearing cartilage histologically.⁵² Incorporation of a-MSCs into scaffolds for surgical implantation has demonstrated success in repairing full-thickness chondral defects with continuous joint surface and extracellular proteins, surface markers, and gene products similar to the native cartilage in animal models.^53,54 In light of the promising basic science and animal studies, clinical studies have begun to emerge.^55-57

Fortier and colleagues⁵⁸ found MRI and histologic evidence of full-thickness chondral repair and increased integration with neighboring cartilage when BMAC was concurrently used at the time of microfracture in an equine model. Fortier and colleagues⁵⁸ also demonstrated greater healing in equine models with acute full-thickness cartilage defects treated by microfracture with MSCs than without delivery of MSCs. Kim and colleagues^59,60 similarly reported superiority in clinical outcomes for patients with osteochondral lesions of the talus treated with marrow stimulation and MSC injection than by the former in isolation.

In humans, stem cell use for chondral repair has additionally proven promising. A systematic review of the literature suggested good to excellent overall outcomes for the treatment of moderate focal chondral defects with BMAC with or without scaffolds and microfracture with inclusion of 8 total publications.⁶¹ This review included Gobbi and colleagues,⁶² who prospectively treated 15 patients with a mean focal chondral defect size of 9.2 cm² about the knee. Use of BMAC covered with a collagen I/III matrix produced significant improvements in patient-reported outcome scores and MRI demonstrated complete hyaline-like cartilage coverage in 80%, with second-look arthroscopy demonstrating normal to nearly normal tissue. Gobbi and colleagues⁵⁵ also found evidence for superiority of chondral defects treated with BMAC compared to matrix-induced autologous chondrocyte implantation (MACI) for patellofemoral lesions in 37 patients (MRI showed complete filling of defects in 81% of BMAC-treated patients vs 76% of MACI-treated patients).

Meniscal Repair

Clinical application of MSCs in the treatment of meniscal pathology is evolving as well. ASCs have been added to modify the biomechanical environment of avascular zone meniscal tears at the time of suture repair in a rabbit, and have demonstrated increased healing rates in small and larger lesions, although the effect lessens with delay in repair.⁶³ Angele and colleagues⁶⁴ treated meniscal defects in a rabbit model with scaffolds with bm-MSCs compared with empty scaffolds or control cohorts and found a higher proportion of menisci with healed meniscus-like fibrocartilage when MSCs were utilized.

In humans, Vangsness and colleagues³⁰ treated knees with partial medial meniscectomy with allogeneic stem cells and reported an increase in meniscal volume and decrease in pain in those patients when compared to a cohort of knees treated with hyaluronic acid. Despite promising early results, additional clinical studies are necessary to determine the external validity and broad applicability of stem cell use in meniscal repair.

Rotator Cuff Repair

The number of local resident stem cells at the site of rotator cuff tear has been shown to decrease with tear size, chronicity, and degree of fatty infiltration, suggesting that those with the greatest need for a good reparative environment are those least equipped to heal.⁶⁵ The need for improvement in this domain is related to the still relatively high re-tear rate after rotator cuff repair despite improvements in instrumentation and surgical technique.⁶⁶ The native fibrocartilaginous transition zone between the humerus and the rotator cuff becomes a fibrovascular scar tissue after rupture and repair with poorer material properties than the native tissue.⁶⁷ Thus, a-MSCs have been evaluated in this setting to determine if the biomechanical and histological properties of the repair may improve.⁶⁸

In rat models, Valencia Mora and colleagues⁶⁸ reported on the application of a-MSCs in a rat rotator cuff repair model compared to an untreated group. They found no differences between those treated rats and those without a-MSCs use in terms of biomechanical properties of the tendon-to-bone healing, but those with stem cell use had less inflammation shown histologically (diminished presence of edema and neutrophils) at 2- and 4-week time points, which the authors suggested may lead to a more elastic repair and less scar at the bone-tendon healing site. Oh and colleagues¹ evaluated the use of a-MSCs in a rabbit subscapularis tear model, and reported significantly reduced fatty infiltration at the site of chronic rotator cuff tear after repair with its application at the repair site; while the load-to-failure was higher in those rabbits with ASCs administration, it was short of reaching statistical significance. Yokoya and colleagues⁶⁹ demonstrated regeneration of rotator cuff tendon-to-bone insertional site anatomy and in the belly of the cuff tendon in a rabbit model with MSCs applied at the operative site. However, Gulotta and colleagues⁷⁰ did not see the same improvement in their similar study in the rat model; these authors failed to see improvement in structure, strength, or composition of the tendinous attachment site despite addition of MSCs.

Clinical studies on augmented rotator cuff repair have also found mixed results. MSCs for this purpose have been cultivated from arthroscopic bone marrow aspiration of the proximal humerus⁷¹ and subacromial bursa⁷² with successful and reproducibly high concentrations of stem cells. Hernigou and colleagues⁷³ found a significant improvement in rate of healing (87% intact cuffs vs 44% in the control group) and repair surface tendon integrity (via ultrasound and MRI) for patients at a minimum of 10 years after rotator cuff repair with MSC injection at the time of surgery. The authors found a direct correlation in these outcomes with the number of MSCs injected at the time of repair. Ellera Gomes and colleagues⁷⁴ injected bm-MSCs obtained from the iliac crest into the tendinous repair site in 14 consecutive patients with full-thickness rotator cuff tears treated by transosseous sutures via a mini-open approach. MRI demonstrated integrity of the repair site in all patients at more than 1-year follow-up.

Achilles Tendon Repair

The goal with stem cell use in Achilles repair is to accelerate the healing and rehabilitation. Several animal studies have demonstrated improved mechanical properties and collagen composition of tendon repairs augmented with stem cells, including Achilles tendon repair in a rat model. Adams and colleagues⁷⁵ compared suture alone (36 tendons) to suture plus stem cell concentrate injection (36 tendons) and stem cell loaded suture (36 tendons) in Achilles tendon repair with rat models. The suture-alone cohort had lower ultimate failure loads at 14 days after surgery, indicating biomechanical superiority with stem cell augmentation means. Transplantation of hypoxic MSCs at the time of Achilles tendon repair may be a promising option for superior biomechanical failure loads and histologic findings as per recent rat model findings by Huang and colleagues.⁷⁶ Yao and colleagues⁷⁷ demonstrated increased strength of suture repair for Achilles repair in rat models at early time points when using MSC-coated suture in comparison to standard suture, and suggested that the addition of stem cells may improve early mechanical properties during the tendon repair process. A-MSC addition to PRP has provided significantly increased tensile strength to rabbit models with Achilles tendon repair as well.⁷⁸

In evaluation of stem cell use for this purpose with humans, Stein and colleagues⁷⁹ reviewed 28 sports-related Achilles tendon ruptures in 27 patients treated with open repair and BMAC injection. At a mean follow-up of 29.7 months, the authors reported no re-ruptures, with 92% return to sport at 5.9 months, and excellent clinical outcomes. This small cohort study found no adverse outcomes related to the BMAC addition, and thus proposed further study of the efficacy of stem cell treatment for Achilles tendon repair.

Anterior Cruciate Ligament Reconstruction

Bm-MSCs genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) have shown great promise in improvement of the formation of mechanically sound tendon-bone interface in anterior cruciate ligament (ACL) reconstruction.⁸⁰ Similar to the other surgical procedures mentioned in this review, animal studies have successfully evaluated the augmentation of osteointegration of tendon to bone in the setting of ACL reconstruction. Jang and colleagues³ investigated the use of nonautologous transplantation of human umbilical cord blood-derived MSCs in a rabbit ACL reconstruction model. The authors demonstrated a lack of immune rejection, and enhanced tendon-bone healing with broad fibrocartilage formation at the transition zone (similar to the native ACL) and decreased femoral and tibial tunnel widening as compared to a control cohort at 12-weeks after surgery. In a rat model, Kanaya and colleagues⁸¹ reported improved histological scores and slight improvements in biomechanical integrity of partially transected rat ACLs treated with intra-articular MSC injection. Stem cell use in the form of suture-supporting scaffolds seeded with MSCs has been evaluated in a total ACL transection rabbit model; the authors of this report demonstrated total ACL regeneration in one-third of samples treated with this augmentation option, in comparison to complete failure in all suture and scaffold alone groups.⁸²

The use of autologous MSCs in ACL healing remains limited to preclinical research and small case series of patients. One human trial by Silva and colleagues⁸³ evaluated the graft-to-bone site of healing in ACL reconstruction for 20 patients who received an intraoperative infiltration of their graft with adult bm-MSCs. MRI and histologic analysis showed no difference in comparison to control groups, but the authors’ conclusion proposed that the number of stem cells injected might have been too minimal to show a clinical effect.

Other Applications

Although outside the scope of this article, stem cells have demonstrated efficacy in the treatment of a number of osseous clinical entities. This includes the treatment of fracture nonunion, augmentation of spinal fusion, and assistance in the treatment of osteonecrosis.⁸⁴

Summary

As a scientific community, our understanding of the use of stem cells, their nuances, and their indications has expanded dramatically over the last several years. Stem cell treatment has particularly infiltrated the world of operative and nonoperative sports medicine, given in part the active patient population seeking greater levels of improvement.⁸⁵ Stem cell therapy offers a potentially effective therapy for a multitude of pathologies because of these cells’ anti-inflammatory, immunoregulatory, angiogenic, and paracrine effects.⁸⁶ It thus remains a very dynamic option in the study of musculoskeletal tissue regeneration. While the potential exists for stem cell use in daily surgery practices, it is still premature to predict whether this can be expected.

The ideal stem cell sources (including allogeneic or autologous), preparation, cell number, timing, and means of application continue to be evaluated, as well as those advantageous pathologies that can benefit from the technology. In order to better answer these pertinent questions, we need to make sure we have a safe, economic, and ethically acceptable means for stem cell translational research efforts. More high-level studies with standardized protocols need to be performed. It is necessary to improve national and international collaboration in research, as well as collaboration with governing bodies, to attempt to further scientific advancement in this field of research.⁴⁹ Further study on embryonic stem cell use may be valuable as well, pending governmental approval. Finally, more dedicated research efforts must be placed on the utility of adjuncts with stem cell use, including PRP and scaffolds, which may increase protection, nutritional support, and mechanical stimulation of the administered stem cells.

Biologic use in orthopedics is a continuously evolving field that complements technical, anatomic, and biomechanical advancements in orthopedics. Biologic agents are receiving increasing attention for their use in augmenting healing of muscles, tendons, ligaments, and osseous structures. As biologic augmentation strategies become increasingly utilized in bony and soft-tissue injuries, research on stem cell use in orthopedics continues to increase. Stem cell-based therapies for the repair or regeneration of muscle and tendon represent a promising technology going forward for numerous diseases.¹

Stem cells by definition are undifferentiated cells that have 4 main characteristics: (1) mobilization during angiogenesis, (2) differentiation into specialized cell types, (3) proliferation and regeneration, and (4) release of immune regulators and growth factors.² Mesenchymal stem cells (MSCs) have garnered the most attention in the field of surgery due to their ability to differentiate into the tissues of interest for the surgeon.³ This includes both bone marrow-derived mesenchymal stem cells (bm-MSCs) and adipose-derived mesenchymal stem cells (a-MSCs). These multipotent stem cells in adults originate from mesenchymal tissues, including bone marrow, tendon, adipose, and muscle tissue.⁴ They are attractive for clinical use because of their multipotent potential and relative ease of growth in culture.⁵ They also exert a paracrine effect to modulate and control inflammation, stimulate endogenous cell repair and proliferation, inhibit apoptosis, and improve blood flow through secretion of chemokines, cytokines, and growth factors.^6,7

Questions exist regarding the best way to administer stem cells, whether systematic administration is possible for these cells to localize to the tissue in need, or more likely if direct application to the pathologic area is necessary.^8,9 A number of sources, purification process, and modes of delivery are available, but the most effective means of preparation and administration are still under investigation. The goal of this review is to illustrate the current state of knowledge surrounding stem cell therapy in orthopedics with a focus on osteoarthritis, tendinopathy, articular cartilage, and enhancement of surgical procedures.

Important Considerations

Common stem cell isolates include embryonic, induced pluripotent, and mesenchymal formulations (Table 1). MSCs can be obtained from multiple sites, including but not limited to the adult bone marrow, adipose, muscular, or tendinous tissues, and their use has been highlighted in the study of numerous orthopedic and nonorthopedic pathologies over the course of the last decade. Research on the use of embryonic stem cells in medical therapy with human implications has received substantial attention, with many ethical concerns by those opposed, and the existence of a potential risk of malignant alterations.^8,10 Amniotic-derived stem cells can be isolated from amniotic fluid, umbilical cord blood, or the placenta and thus do not harbor the same social constraints as the aforementioned embryonic cells; however, they do not harbor the same magnitude of multi-differentiation potential, either.⁴

Adult MSCs are more locally available and easy to obtain for treatment when compared with embryonic and fetal stem cells, and the former has a lower immunogenicity, which allows allogeneic use.¹¹ Safety has been preliminarily demonstrated in use thus far; Centeno and colleagues¹² found no neoplastic tissue generation at the site of stem cell injection after 3 years postinjection for a cohort of patients who were treated with autologous bm-MSCs for various pathologies. Self-limited pain and swelling are the most commonly reported adverse events after use.¹³ However, long-term data are lacking in many instances to definitively suggest the absence of possible complications.

Basic Science

Stem cell research encompasses a wide range of rapidly developing treatment strategies that are applicable to virtually every field of medicine. In general, stem cells can be classified as embryonic stem cells (ESCs), induced pluripotent stem (iPS) cells, or adult-derived MSCs. ESCs are embryonic cells derived typically from fetal tissue, whereas iPS cells are dedifferentiated from adult tissue, thus avoiding many of the ethical and legal challenges imposed by research with ESCs. However, oncogenic and lingering politico-legal concerns with introducing dedifferentiated ESCs or iPS cells into healthy tissue necessitate the development, isolation, and expansion of multi- but not pluripotent stem cell lines.¹⁴ To date, the most advantageous and widely utilized from any perspective are MSCs, which can further differentiate into cartilage, tendon, muscle, and bony tissue.^7,15,16

MSCs are defined by their ability to demonstrate in vitro differentiation into osteoblasts, adipocytes, or chondroblasts, adhere to plastic, express CD105, CD73, and CD90, and not express CD43, CD23, CD14 or CD11b, CD79 or CD19, or HLA-DR.¹⁷ Porada and Almeida-Porada¹⁸ have outlined 6 reasons highlighting the advantages of MSCs: 1) ease of isolation, 2) high differentiation capabilities, 3) strong colony expansion without differentiation loss, 4) immunosuppression following transplantation, 5) powerful anti-inflammatory properties, and 6) their ability to localize to damaged tissue. The anti-inflammatory properties of MSCs are particularly important as they promote allo- and xenotransplantation from donor tissues.^19,20 MSCs can be isolated from numerous sources, including but not limited to bone marrow, periosteum, adipocyte, and muscle.^21-23 Interestingly, the source tissue used to isolate MSCs can affect differentiation capabilities, colony size, and growth rate (Table 2).²⁴ Advantages of a-MSCs include high prevalence and ease of harvest; however, several animal studies have shown inferior results when compared to bm-MSCs.^25-27 More research is needed to determine the ideal source material for MSCs, which will likely depend in part on the procedure for which they are employed.²⁷

Following harvesting, isolation, and expansion, MSC delivery methods for treatments typically consist of either cell-based or tissue engineering approaches. Cell-based techniques involve the injection of MSCs into damaged tissues. Purely cell-based therapy has shown success in limited clinical trials involving knee osteoarthritis, cartilage repair, and meniscal repair.^28-30 However, additional studies with longer follow-up are required to validate these preliminary findings. Tissue engineering approaches involve the construction of a 3-dimensional scaffold seeded with MSCs that is later surgically implanted. While promising in theory, limited and often conflicting data exist regarding the efficacy of tissue-engineered MSC implantation.^31-32 Suboptimal scaffold vascularity is a major limitation to scaffold design, which may be alleviated in part with the advent of 3-dimensional printing and the ability to more precisely alter scaffold architecture.^14,33 Additional limitations include ensuring MSC purity and differentiation potential following harvesting and expansion. At present, the use of tissue engineering with MSCs is promising but it remains a nascent technology with additional preclinical studies required to confirm implant efficacy and safety.

Clinical Entities

Osteoarthritis

MSC therapies have emerged as promising treatment strategies in the setting of early osteoarthritis (OA). In addition to their regenerative potential, MSCs demonstrate potent anti-inflammatory properties, increasing their attractiveness as biologic agents in the setting of OA.³⁴ Over the past decade, multiple human trials have been published demonstrating the efficacy of MSC injections into patients with OA.^35,36 In a study evaluating a-MSC injection into elderly patients (age >65 years) with knee OA, Koh and colleagues²⁹ found that 88% demonstrated improved cartilage status at 2-year follow-up, while no patient underwent a total knee arthroplasty during this time period. In another study investigating patients with unicompartmental knee OA with varus alignment undergoing high tibial osteotomy and microfracture, Wong and colleagues³⁷ reported improved clinical, patient-reported, and magnetic resonance imaging (MRI)-based outcomes in a group receiving a preoperative MSC injection compared to a control group. Further, in a recent randomized control trial of patients with knee osteoarthritis, Vega and colleagues³⁸ reported improved cartilage and quality of life outcomes at 1 year following MSC injection compared to a control group receiving a hyaluronic acid injection. In addition to knee OA, studies have also reported improvement in ankle OA following MSC injection.³⁹ While promising, many of the preliminary clinical studies evaluating the efficacy of MSC therapies in the treatment of OA are hindered by small patient populations and short-term follow-up. Additional large-scale, randomized studies are required and many are ongoing presently in hopes of validating these preliminary findings.³⁶

Tendinopathy

The quality of repaired tissue in primary tendon-to-tendon and tendon-to-bone healing has long been a topic of great interest.⁴⁰ The healing potential of tendons is inferior to that of other bony and connective tissues,⁴¹ with tendon healing typically resulting in a biomechanically and histologically inferior structure to the native tissue.⁴² As such, this has been a particularly salient opportunity for stem cell use with hopes of recapitulating a more normal tendon or tendon enthesis following injury. In addition to the acute injury, there is great interest in the application of stem cells to chronic states of injury such as tendinopathy.

In equine models, the effect of autologous bm-MSCs treatment on tendinopathy of the superficial digital flexor tendon has been studied. Godwin and colleagues⁴³ evaluated 141 race horses with spontaneous superficial digital flexor tendinopathy treated in this manner, and reported a reinjury percentage in these treated horses of just 27.4%, which compared favorably to historical controls and alternative therapeutics. Machova Urdzikova and colleagues⁴⁴ injected MSCs at Achilles tendinopathy locations to augment nonoperative healing in 40 rats, and identified more native histological organization and improved vascularization in comparison to control rat specimens. Oshita and colleagues⁴⁵ reported histologic improvement of tendinopathy findings in 8 rats receiving a-MSCs at the location of induced Achilles tendinopathy that was significantly superior to a control cohort. Bm-MSCs were used by Yuksel and colleagues⁴⁶ in comparison with platelet-rich plasma (PRP) for treatment of Achilles tendon ruptures created surgically in rat models. They demonstrated successful effects with its use in terms of recovery for the tendon’s histopathologic, immunohistochemical, and biomechanical properties, related to significantly greater levels of anti-inflammatory cytokines. However, these aforementioned findings have not been uniform across the literature—other authors have reported findings that MSC transplantation alone did not repair Achilles tendon injury with such high levels of success.⁴⁷

Human treatment of tendinopathies with stem cells has been scarcely studied to date. Pascual-Garrido and colleagues⁴⁸ evaluated 8 patients with refractory patellar tendinopathy treated with injection of autologous bm-MSCs and reported successful results at 2- to 5-year follow-up, with significant improvements in patient-reported outcome measures for 100% of patients. Seven of 8 (87.5%) noted that they would undergo the procedure again.

Articular Cartilage Injury

Chondral injury is a particularly important subject given the limited potential of chondrocytes to replicate or migrate to the site of pathology.⁴⁹ Stem cell use in this setting assists with programmed growth factor release and alteration of the anatomic microenvironment to facilitate regeneration and repair of the chondral surface. Autologous stem cell use through microfracture provides a perforation into the bone marrow and a subsequent fibrin clot formation containing platelets, growth factors, vascular elements, and MSCs.⁵⁰ A similar concept to PRP is currently being explored with bm-MSCs. Isolated bm-MSCs are commonly referred to as bone marrow aspirate or bone marrow aspirate concentrate (BMAC). Commercially available systems are now available to aid in the harvesting and implementation of BMAC. One of the more promising avenues for BMAC implementation is in articular cartilage repair or regeneration due to chondrogenic potential of BMAC when used in isolation or when combined with microfracture, chondrocyte transfer, or collagen scaffolds.^19,51 Synovial-derived stem cells as an additional source for stem cell use has demonstrated excellent chondrogenic potential in animal studies with full-thickness lesion healing and native-appearing cartilage histologically.⁵² Incorporation of a-MSCs into scaffolds for surgical implantation has demonstrated success in repairing full-thickness chondral defects with continuous joint surface and extracellular proteins, surface markers, and gene products similar to the native cartilage in animal models.^53,54 In light of the promising basic science and animal studies, clinical studies have begun to emerge.^55-57

Fortier and colleagues⁵⁸ found MRI and histologic evidence of full-thickness chondral repair and increased integration with neighboring cartilage when BMAC was concurrently used at the time of microfracture in an equine model. Fortier and colleagues⁵⁸ also demonstrated greater healing in equine models with acute full-thickness cartilage defects treated by microfracture with MSCs than without delivery of MSCs. Kim and colleagues^59,60 similarly reported superiority in clinical outcomes for patients with osteochondral lesions of the talus treated with marrow stimulation and MSC injection than by the former in isolation.

In humans, stem cell use for chondral repair has additionally proven promising. A systematic review of the literature suggested good to excellent overall outcomes for the treatment of moderate focal chondral defects with BMAC with or without scaffolds and microfracture with inclusion of 8 total publications.⁶¹ This review included Gobbi and colleagues,⁶² who prospectively treated 15 patients with a mean focal chondral defect size of 9.2 cm² about the knee. Use of BMAC covered with a collagen I/III matrix produced significant improvements in patient-reported outcome scores and MRI demonstrated complete hyaline-like cartilage coverage in 80%, with second-look arthroscopy demonstrating normal to nearly normal tissue. Gobbi and colleagues⁵⁵ also found evidence for superiority of chondral defects treated with BMAC compared to matrix-induced autologous chondrocyte implantation (MACI) for patellofemoral lesions in 37 patients (MRI showed complete filling of defects in 81% of BMAC-treated patients vs 76% of MACI-treated patients).

Meniscal Repair

Clinical application of MSCs in the treatment of meniscal pathology is evolving as well. ASCs have been added to modify the biomechanical environment of avascular zone meniscal tears at the time of suture repair in a rabbit, and have demonstrated increased healing rates in small and larger lesions, although the effect lessens with delay in repair.⁶³ Angele and colleagues⁶⁴ treated meniscal defects in a rabbit model with scaffolds with bm-MSCs compared with empty scaffolds or control cohorts and found a higher proportion of menisci with healed meniscus-like fibrocartilage when MSCs were utilized.

In humans, Vangsness and colleagues³⁰ treated knees with partial medial meniscectomy with allogeneic stem cells and reported an increase in meniscal volume and decrease in pain in those patients when compared to a cohort of knees treated with hyaluronic acid. Despite promising early results, additional clinical studies are necessary to determine the external validity and broad applicability of stem cell use in meniscal repair.

Rotator Cuff Repair

The number of local resident stem cells at the site of rotator cuff tear has been shown to decrease with tear size, chronicity, and degree of fatty infiltration, suggesting that those with the greatest need for a good reparative environment are those least equipped to heal.⁶⁵ The need for improvement in this domain is related to the still relatively high re-tear rate after rotator cuff repair despite improvements in instrumentation and surgical technique.⁶⁶ The native fibrocartilaginous transition zone between the humerus and the rotator cuff becomes a fibrovascular scar tissue after rupture and repair with poorer material properties than the native tissue.⁶⁷ Thus, a-MSCs have been evaluated in this setting to determine if the biomechanical and histological properties of the repair may improve.⁶⁸

In rat models, Valencia Mora and colleagues⁶⁸ reported on the application of a-MSCs in a rat rotator cuff repair model compared to an untreated group. They found no differences between those treated rats and those without a-MSCs use in terms of biomechanical properties of the tendon-to-bone healing, but those with stem cell use had less inflammation shown histologically (diminished presence of edema and neutrophils) at 2- and 4-week time points, which the authors suggested may lead to a more elastic repair and less scar at the bone-tendon healing site. Oh and colleagues¹ evaluated the use of a-MSCs in a rabbit subscapularis tear model, and reported significantly reduced fatty infiltration at the site of chronic rotator cuff tear after repair with its application at the repair site; while the load-to-failure was higher in those rabbits with ASCs administration, it was short of reaching statistical significance. Yokoya and colleagues⁶⁹ demonstrated regeneration of rotator cuff tendon-to-bone insertional site anatomy and in the belly of the cuff tendon in a rabbit model with MSCs applied at the operative site. However, Gulotta and colleagues⁷⁰ did not see the same improvement in their similar study in the rat model; these authors failed to see improvement in structure, strength, or composition of the tendinous attachment site despite addition of MSCs.

Clinical studies on augmented rotator cuff repair have also found mixed results. MSCs for this purpose have been cultivated from arthroscopic bone marrow aspiration of the proximal humerus⁷¹ and subacromial bursa⁷² with successful and reproducibly high concentrations of stem cells. Hernigou and colleagues⁷³ found a significant improvement in rate of healing (87% intact cuffs vs 44% in the control group) and repair surface tendon integrity (via ultrasound and MRI) for patients at a minimum of 10 years after rotator cuff repair with MSC injection at the time of surgery. The authors found a direct correlation in these outcomes with the number of MSCs injected at the time of repair. Ellera Gomes and colleagues⁷⁴ injected bm-MSCs obtained from the iliac crest into the tendinous repair site in 14 consecutive patients with full-thickness rotator cuff tears treated by transosseous sutures via a mini-open approach. MRI demonstrated integrity of the repair site in all patients at more than 1-year follow-up.

Achilles Tendon Repair

The goal with stem cell use in Achilles repair is to accelerate the healing and rehabilitation. Several animal studies have demonstrated improved mechanical properties and collagen composition of tendon repairs augmented with stem cells, including Achilles tendon repair in a rat model. Adams and colleagues⁷⁵ compared suture alone (36 tendons) to suture plus stem cell concentrate injection (36 tendons) and stem cell loaded suture (36 tendons) in Achilles tendon repair with rat models. The suture-alone cohort had lower ultimate failure loads at 14 days after surgery, indicating biomechanical superiority with stem cell augmentation means. Transplantation of hypoxic MSCs at the time of Achilles tendon repair may be a promising option for superior biomechanical failure loads and histologic findings as per recent rat model findings by Huang and colleagues.⁷⁶ Yao and colleagues⁷⁷ demonstrated increased strength of suture repair for Achilles repair in rat models at early time points when using MSC-coated suture in comparison to standard suture, and suggested that the addition of stem cells may improve early mechanical properties during the tendon repair process. A-MSC addition to PRP has provided significantly increased tensile strength to rabbit models with Achilles tendon repair as well.⁷⁸

In evaluation of stem cell use for this purpose with humans, Stein and colleagues⁷⁹ reviewed 28 sports-related Achilles tendon ruptures in 27 patients treated with open repair and BMAC injection. At a mean follow-up of 29.7 months, the authors reported no re-ruptures, with 92% return to sport at 5.9 months, and excellent clinical outcomes. This small cohort study found no adverse outcomes related to the BMAC addition, and thus proposed further study of the efficacy of stem cell treatment for Achilles tendon repair.

Anterior Cruciate Ligament Reconstruction

Bm-MSCs genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) have shown great promise in improvement of the formation of mechanically sound tendon-bone interface in anterior cruciate ligament (ACL) reconstruction.⁸⁰ Similar to the other surgical procedures mentioned in this review, animal studies have successfully evaluated the augmentation of osteointegration of tendon to bone in the setting of ACL reconstruction. Jang and colleagues³ investigated the use of nonautologous transplantation of human umbilical cord blood-derived MSCs in a rabbit ACL reconstruction model. The authors demonstrated a lack of immune rejection, and enhanced tendon-bone healing with broad fibrocartilage formation at the transition zone (similar to the native ACL) and decreased femoral and tibial tunnel widening as compared to a control cohort at 12-weeks after surgery. In a rat model, Kanaya and colleagues⁸¹ reported improved histological scores and slight improvements in biomechanical integrity of partially transected rat ACLs treated with intra-articular MSC injection. Stem cell use in the form of suture-supporting scaffolds seeded with MSCs has been evaluated in a total ACL transection rabbit model; the authors of this report demonstrated total ACL regeneration in one-third of samples treated with this augmentation option, in comparison to complete failure in all suture and scaffold alone groups.⁸²

The use of autologous MSCs in ACL healing remains limited to preclinical research and small case series of patients. One human trial by Silva and colleagues⁸³ evaluated the graft-to-bone site of healing in ACL reconstruction for 20 patients who received an intraoperative infiltration of their graft with adult bm-MSCs. MRI and histologic analysis showed no difference in comparison to control groups, but the authors’ conclusion proposed that the number of stem cells injected might have been too minimal to show a clinical effect.

Other Applications

Although outside the scope of this article, stem cells have demonstrated efficacy in the treatment of a number of osseous clinical entities. This includes the treatment of fracture nonunion, augmentation of spinal fusion, and assistance in the treatment of osteonecrosis.⁸⁴

Summary

As a scientific community, our understanding of the use of stem cells, their nuances, and their indications has expanded dramatically over the last several years. Stem cell treatment has particularly infiltrated the world of operative and nonoperative sports medicine, given in part the active patient population seeking greater levels of improvement.⁸⁵ Stem cell therapy offers a potentially effective therapy for a multitude of pathologies because of these cells’ anti-inflammatory, immunoregulatory, angiogenic, and paracrine effects.⁸⁶ It thus remains a very dynamic option in the study of musculoskeletal tissue regeneration. While the potential exists for stem cell use in daily surgery practices, it is still premature to predict whether this can be expected.

The ideal stem cell sources (including allogeneic or autologous), preparation, cell number, timing, and means of application continue to be evaluated, as well as those advantageous pathologies that can benefit from the technology. In order to better answer these pertinent questions, we need to make sure we have a safe, economic, and ethically acceptable means for stem cell translational research efforts. More high-level studies with standardized protocols need to be performed. It is necessary to improve national and international collaboration in research, as well as collaboration with governing bodies, to attempt to further scientific advancement in this field of research.⁴⁹ Further study on embryonic stem cell use may be valuable as well, pending governmental approval. Finally, more dedicated research efforts must be placed on the utility of adjuncts with stem cell use, including PRP and scaffolds, which may increase protection, nutritional support, and mechanical stimulation of the administered stem cells.

Biologic use in orthopedics is a continuously evolving field that complements technical, anatomic, and biomechanical advancements in orthopedics. Biologic agents are receiving increasing attention for their use in augmenting healing of muscles, tendons, ligaments, and osseous structures. As biologic augmentation strategies become increasingly utilized in bony and soft-tissue injuries, research on stem cell use in orthopedics continues to increase. Stem cell-based therapies for the repair or regeneration of muscle and tendon represent a promising technology going forward for numerous diseases.¹

Stem cells by definition are undifferentiated cells that have 4 main characteristics: (1) mobilization during angiogenesis, (2) differentiation into specialized cell types, (3) proliferation and regeneration, and (4) release of immune regulators and growth factors.² Mesenchymal stem cells (MSCs) have garnered the most attention in the field of surgery due to their ability to differentiate into the tissues of interest for the surgeon.³ This includes both bone marrow-derived mesenchymal stem cells (bm-MSCs) and adipose-derived mesenchymal stem cells (a-MSCs). These multipotent stem cells in adults originate from mesenchymal tissues, including bone marrow, tendon, adipose, and muscle tissue.⁴ They are attractive for clinical use because of their multipotent potential and relative ease of growth in culture.⁵ They also exert a paracrine effect to modulate and control inflammation, stimulate endogenous cell repair and proliferation, inhibit apoptosis, and improve blood flow through secretion of chemokines, cytokines, and growth factors.^6,7

Questions exist regarding the best way to administer stem cells, whether systematic administration is possible for these cells to localize to the tissue in need, or more likely if direct application to the pathologic area is necessary.^8,9 A number of sources, purification process, and modes of delivery are available, but the most effective means of preparation and administration are still under investigation. The goal of this review is to illustrate the current state of knowledge surrounding stem cell therapy in orthopedics with a focus on osteoarthritis, tendinopathy, articular cartilage, and enhancement of surgical procedures.

Important Considerations

Common stem cell isolates include embryonic, induced pluripotent, and mesenchymal formulations (Table 1). MSCs can be obtained from multiple sites, including but not limited to the adult bone marrow, adipose, muscular, or tendinous tissues, and their use has been highlighted in the study of numerous orthopedic and nonorthopedic pathologies over the course of the last decade. Research on the use of embryonic stem cells in medical therapy with human implications has received substantial attention, with many ethical concerns by those opposed, and the existence of a potential risk of malignant alterations.^8,10 Amniotic-derived stem cells can be isolated from amniotic fluid, umbilical cord blood, or the placenta and thus do not harbor the same social constraints as the aforementioned embryonic cells; however, they do not harbor the same magnitude of multi-differentiation potential, either.⁴

Adult MSCs are more locally available and easy to obtain for treatment when compared with embryonic and fetal stem cells, and the former has a lower immunogenicity, which allows allogeneic use.¹¹ Safety has been preliminarily demonstrated in use thus far; Centeno and colleagues¹² found no neoplastic tissue generation at the site of stem cell injection after 3 years postinjection for a cohort of patients who were treated with autologous bm-MSCs for various pathologies. Self-limited pain and swelling are the most commonly reported adverse events after use.¹³ However, long-term data are lacking in many instances to definitively suggest the absence of possible complications.

Basic Science

Stem cell research encompasses a wide range of rapidly developing treatment strategies that are applicable to virtually every field of medicine. In general, stem cells can be classified as embryonic stem cells (ESCs), induced pluripotent stem (iPS) cells, or adult-derived MSCs. ESCs are embryonic cells derived typically from fetal tissue, whereas iPS cells are dedifferentiated from adult tissue, thus avoiding many of the ethical and legal challenges imposed by research with ESCs. However, oncogenic and lingering politico-legal concerns with introducing dedifferentiated ESCs or iPS cells into healthy tissue necessitate the development, isolation, and expansion of multi- but not pluripotent stem cell lines.¹⁴ To date, the most advantageous and widely utilized from any perspective are MSCs, which can further differentiate into cartilage, tendon, muscle, and bony tissue.^7,15,16

MSCs are defined by their ability to demonstrate in vitro differentiation into osteoblasts, adipocytes, or chondroblasts, adhere to plastic, express CD105, CD73, and CD90, and not express CD43, CD23, CD14 or CD11b, CD79 or CD19, or HLA-DR.¹⁷ Porada and Almeida-Porada¹⁸ have outlined 6 reasons highlighting the advantages of MSCs: 1) ease of isolation, 2) high differentiation capabilities, 3) strong colony expansion without differentiation loss, 4) immunosuppression following transplantation, 5) powerful anti-inflammatory properties, and 6) their ability to localize to damaged tissue. The anti-inflammatory properties of MSCs are particularly important as they promote allo- and xenotransplantation from donor tissues.^19,20 MSCs can be isolated from numerous sources, including but not limited to bone marrow, periosteum, adipocyte, and muscle.^21-23 Interestingly, the source tissue used to isolate MSCs can affect differentiation capabilities, colony size, and growth rate (Table 2).²⁴ Advantages of a-MSCs include high prevalence and ease of harvest; however, several animal studies have shown inferior results when compared to bm-MSCs.^25-27 More research is needed to determine the ideal source material for MSCs, which will likely depend in part on the procedure for which they are employed.²⁷

Following harvesting, isolation, and expansion, MSC delivery methods for treatments typically consist of either cell-based or tissue engineering approaches. Cell-based techniques involve the injection of MSCs into damaged tissues. Purely cell-based therapy has shown success in limited clinical trials involving knee osteoarthritis, cartilage repair, and meniscal repair.^28-30 However, additional studies with longer follow-up are required to validate these preliminary findings. Tissue engineering approaches involve the construction of a 3-dimensional scaffold seeded with MSCs that is later surgically implanted. While promising in theory, limited and often conflicting data exist regarding the efficacy of tissue-engineered MSC implantation.^31-32 Suboptimal scaffold vascularity is a major limitation to scaffold design, which may be alleviated in part with the advent of 3-dimensional printing and the ability to more precisely alter scaffold architecture.^14,33 Additional limitations include ensuring MSC purity and differentiation potential following harvesting and expansion. At present, the use of tissue engineering with MSCs is promising but it remains a nascent technology with additional preclinical studies required to confirm implant efficacy and safety.

Clinical Entities

Osteoarthritis

MSC therapies have emerged as promising treatment strategies in the setting of early osteoarthritis (OA). In addition to their regenerative potential, MSCs demonstrate potent anti-inflammatory properties, increasing their attractiveness as biologic agents in the setting of OA.³⁴ Over the past decade, multiple human trials have been published demonstrating the efficacy of MSC injections into patients with OA.^35,36 In a study evaluating a-MSC injection into elderly patients (age >65 years) with knee OA, Koh and colleagues²⁹ found that 88% demonstrated improved cartilage status at 2-year follow-up, while no patient underwent a total knee arthroplasty during this time period. In another study investigating patients with unicompartmental knee OA with varus alignment undergoing high tibial osteotomy and microfracture, Wong and colleagues³⁷ reported improved clinical, patient-reported, and magnetic resonance imaging (MRI)-based outcomes in a group receiving a preoperative MSC injection compared to a control group. Further, in a recent randomized control trial of patients with knee osteoarthritis, Vega and colleagues³⁸ reported improved cartilage and quality of life outcomes at 1 year following MSC injection compared to a control group receiving a hyaluronic acid injection. In addition to knee OA, studies have also reported improvement in ankle OA following MSC injection.³⁹ While promising, many of the preliminary clinical studies evaluating the efficacy of MSC therapies in the treatment of OA are hindered by small patient populations and short-term follow-up. Additional large-scale, randomized studies are required and many are ongoing presently in hopes of validating these preliminary findings.³⁶

Tendinopathy

The quality of repaired tissue in primary tendon-to-tendon and tendon-to-bone healing has long been a topic of great interest.⁴⁰ The healing potential of tendons is inferior to that of other bony and connective tissues,⁴¹ with tendon healing typically resulting in a biomechanically and histologically inferior structure to the native tissue.⁴² As such, this has been a particularly salient opportunity for stem cell use with hopes of recapitulating a more normal tendon or tendon enthesis following injury. In addition to the acute injury, there is great interest in the application of stem cells to chronic states of injury such as tendinopathy.

In equine models, the effect of autologous bm-MSCs treatment on tendinopathy of the superficial digital flexor tendon has been studied. Godwin and colleagues⁴³ evaluated 141 race horses with spontaneous superficial digital flexor tendinopathy treated in this manner, and reported a reinjury percentage in these treated horses of just 27.4%, which compared favorably to historical controls and alternative therapeutics. Machova Urdzikova and colleagues⁴⁴ injected MSCs at Achilles tendinopathy locations to augment nonoperative healing in 40 rats, and identified more native histological organization and improved vascularization in comparison to control rat specimens. Oshita and colleagues⁴⁵ reported histologic improvement of tendinopathy findings in 8 rats receiving a-MSCs at the location of induced Achilles tendinopathy that was significantly superior to a control cohort. Bm-MSCs were used by Yuksel and colleagues⁴⁶ in comparison with platelet-rich plasma (PRP) for treatment of Achilles tendon ruptures created surgically in rat models. They demonstrated successful effects with its use in terms of recovery for the tendon’s histopathologic, immunohistochemical, and biomechanical properties, related to significantly greater levels of anti-inflammatory cytokines. However, these aforementioned findings have not been uniform across the literature—other authors have reported findings that MSC transplantation alone did not repair Achilles tendon injury with such high levels of success.⁴⁷

Human treatment of tendinopathies with stem cells has been scarcely studied to date. Pascual-Garrido and colleagues⁴⁸ evaluated 8 patients with refractory patellar tendinopathy treated with injection of autologous bm-MSCs and reported successful results at 2- to 5-year follow-up, with significant improvements in patient-reported outcome measures for 100% of patients. Seven of 8 (87.5%) noted that they would undergo the procedure again.

Articular Cartilage Injury

Chondral injury is a particularly important subject given the limited potential of chondrocytes to replicate or migrate to the site of pathology.⁴⁹ Stem cell use in this setting assists with programmed growth factor release and alteration of the anatomic microenvironment to facilitate regeneration and repair of the chondral surface. Autologous stem cell use through microfracture provides a perforation into the bone marrow and a subsequent fibrin clot formation containing platelets, growth factors, vascular elements, and MSCs.⁵⁰ A similar concept to PRP is currently being explored with bm-MSCs. Isolated bm-MSCs are commonly referred to as bone marrow aspirate or bone marrow aspirate concentrate (BMAC). Commercially available systems are now available to aid in the harvesting and implementation of BMAC. One of the more promising avenues for BMAC implementation is in articular cartilage repair or regeneration due to chondrogenic potential of BMAC when used in isolation or when combined with microfracture, chondrocyte transfer, or collagen scaffolds.^19,51 Synovial-derived stem cells as an additional source for stem cell use has demonstrated excellent chondrogenic potential in animal studies with full-thickness lesion healing and native-appearing cartilage histologically.⁵² Incorporation of a-MSCs into scaffolds for surgical implantation has demonstrated success in repairing full-thickness chondral defects with continuous joint surface and extracellular proteins, surface markers, and gene products similar to the native cartilage in animal models.^53,54 In light of the promising basic science and animal studies, clinical studies have begun to emerge.^55-57

Fortier and colleagues⁵⁸ found MRI and histologic evidence of full-thickness chondral repair and increased integration with neighboring cartilage when BMAC was concurrently used at the time of microfracture in an equine model. Fortier and colleagues⁵⁸ also demonstrated greater healing in equine models with acute full-thickness cartilage defects treated by microfracture with MSCs than without delivery of MSCs. Kim and colleagues^59,60 similarly reported superiority in clinical outcomes for patients with osteochondral lesions of the talus treated with marrow stimulation and MSC injection than by the former in isolation.

In humans, stem cell use for chondral repair has additionally proven promising. A systematic review of the literature suggested good to excellent overall outcomes for the treatment of moderate focal chondral defects with BMAC with or without scaffolds and microfracture with inclusion of 8 total publications.⁶¹ This review included Gobbi and colleagues,⁶² who prospectively treated 15 patients with a mean focal chondral defect size of 9.2 cm² about the knee. Use of BMAC covered with a collagen I/III matrix produced significant improvements in patient-reported outcome scores and MRI demonstrated complete hyaline-like cartilage coverage in 80%, with second-look arthroscopy demonstrating normal to nearly normal tissue. Gobbi and colleagues⁵⁵ also found evidence for superiority of chondral defects treated with BMAC compared to matrix-induced autologous chondrocyte implantation (MACI) for patellofemoral lesions in 37 patients (MRI showed complete filling of defects in 81% of BMAC-treated patients vs 76% of MACI-treated patients).

Meniscal Repair

Clinical application of MSCs in the treatment of meniscal pathology is evolving as well. ASCs have been added to modify the biomechanical environment of avascular zone meniscal tears at the time of suture repair in a rabbit, and have demonstrated increased healing rates in small and larger lesions, although the effect lessens with delay in repair.⁶³ Angele and colleagues⁶⁴ treated meniscal defects in a rabbit model with scaffolds with bm-MSCs compared with empty scaffolds or control cohorts and found a higher proportion of menisci with healed meniscus-like fibrocartilage when MSCs were utilized.

In humans, Vangsness and colleagues³⁰ treated knees with partial medial meniscectomy with allogeneic stem cells and reported an increase in meniscal volume and decrease in pain in those patients when compared to a cohort of knees treated with hyaluronic acid. Despite promising early results, additional clinical studies are necessary to determine the external validity and broad applicability of stem cell use in meniscal repair.

Rotator Cuff Repair

The number of local resident stem cells at the site of rotator cuff tear has been shown to decrease with tear size, chronicity, and degree of fatty infiltration, suggesting that those with the greatest need for a good reparative environment are those least equipped to heal.⁶⁵ The need for improvement in this domain is related to the still relatively high re-tear rate after rotator cuff repair despite improvements in instrumentation and surgical technique.⁶⁶ The native fibrocartilaginous transition zone between the humerus and the rotator cuff becomes a fibrovascular scar tissue after rupture and repair with poorer material properties than the native tissue.⁶⁷ Thus, a-MSCs have been evaluated in this setting to determine if the biomechanical and histological properties of the repair may improve.⁶⁸

In rat models, Valencia Mora and colleagues⁶⁸ reported on the application of a-MSCs in a rat rotator cuff repair model compared to an untreated group. They found no differences between those treated rats and those without a-MSCs use in terms of biomechanical properties of the tendon-to-bone healing, but those with stem cell use had less inflammation shown histologically (diminished presence of edema and neutrophils) at 2- and 4-week time points, which the authors suggested may lead to a more elastic repair and less scar at the bone-tendon healing site. Oh and colleagues¹ evaluated the use of a-MSCs in a rabbit subscapularis tear model, and reported significantly reduced fatty infiltration at the site of chronic rotator cuff tear after repair with its application at the repair site; while the load-to-failure was higher in those rabbits with ASCs administration, it was short of reaching statistical significance. Yokoya and colleagues⁶⁹ demonstrated regeneration of rotator cuff tendon-to-bone insertional site anatomy and in the belly of the cuff tendon in a rabbit model with MSCs applied at the operative site. However, Gulotta and colleagues⁷⁰ did not see the same improvement in their similar study in the rat model; these authors failed to see improvement in structure, strength, or composition of the tendinous attachment site despite addition of MSCs.

Clinical studies on augmented rotator cuff repair have also found mixed results. MSCs for this purpose have been cultivated from arthroscopic bone marrow aspiration of the proximal humerus⁷¹ and subacromial bursa⁷² with successful and reproducibly high concentrations of stem cells. Hernigou and colleagues⁷³ found a significant improvement in rate of healing (87% intact cuffs vs 44% in the control group) and repair surface tendon integrity (via ultrasound and MRI) for patients at a minimum of 10 years after rotator cuff repair with MSC injection at the time of surgery. The authors found a direct correlation in these outcomes with the number of MSCs injected at the time of repair. Ellera Gomes and colleagues⁷⁴ injected bm-MSCs obtained from the iliac crest into the tendinous repair site in 14 consecutive patients with full-thickness rotator cuff tears treated by transosseous sutures via a mini-open approach. MRI demonstrated integrity of the repair site in all patients at more than 1-year follow-up.

Achilles Tendon Repair

The goal with stem cell use in Achilles repair is to accelerate the healing and rehabilitation. Several animal studies have demonstrated improved mechanical properties and collagen composition of tendon repairs augmented with stem cells, including Achilles tendon repair in a rat model. Adams and colleagues⁷⁵ compared suture alone (36 tendons) to suture plus stem cell concentrate injection (36 tendons) and stem cell loaded suture (36 tendons) in Achilles tendon repair with rat models. The suture-alone cohort had lower ultimate failure loads at 14 days after surgery, indicating biomechanical superiority with stem cell augmentation means. Transplantation of hypoxic MSCs at the time of Achilles tendon repair may be a promising option for superior biomechanical failure loads and histologic findings as per recent rat model findings by Huang and colleagues.⁷⁶ Yao and colleagues⁷⁷ demonstrated increased strength of suture repair for Achilles repair in rat models at early time points when using MSC-coated suture in comparison to standard suture, and suggested that the addition of stem cells may improve early mechanical properties during the tendon repair process. A-MSC addition to PRP has provided significantly increased tensile strength to rabbit models with Achilles tendon repair as well.⁷⁸

In evaluation of stem cell use for this purpose with humans, Stein and colleagues⁷⁹ reviewed 28 sports-related Achilles tendon ruptures in 27 patients treated with open repair and BMAC injection. At a mean follow-up of 29.7 months, the authors reported no re-ruptures, with 92% return to sport at 5.9 months, and excellent clinical outcomes. This small cohort study found no adverse outcomes related to the BMAC addition, and thus proposed further study of the efficacy of stem cell treatment for Achilles tendon repair.

Anterior Cruciate Ligament Reconstruction

Bm-MSCs genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) have shown great promise in improvement of the formation of mechanically sound tendon-bone interface in anterior cruciate ligament (ACL) reconstruction.⁸⁰ Similar to the other surgical procedures mentioned in this review, animal studies have successfully evaluated the augmentation of osteointegration of tendon to bone in the setting of ACL reconstruction. Jang and colleagues³ investigated the use of nonautologous transplantation of human umbilical cord blood-derived MSCs in a rabbit ACL reconstruction model. The authors demonstrated a lack of immune rejection, and enhanced tendon-bone healing with broad fibrocartilage formation at the transition zone (similar to the native ACL) and decreased femoral and tibial tunnel widening as compared to a control cohort at 12-weeks after surgery. In a rat model, Kanaya and colleagues⁸¹ reported improved histological scores and slight improvements in biomechanical integrity of partially transected rat ACLs treated with intra-articular MSC injection. Stem cell use in the form of suture-supporting scaffolds seeded with MSCs has been evaluated in a total ACL transection rabbit model; the authors of this report demonstrated total ACL regeneration in one-third of samples treated with this augmentation option, in comparison to complete failure in all suture and scaffold alone groups.⁸²

The use of autologous MSCs in ACL healing remains limited to preclinical research and small case series of patients. One human trial by Silva and colleagues⁸³ evaluated the graft-to-bone site of healing in ACL reconstruction for 20 patients who received an intraoperative infiltration of their graft with adult bm-MSCs. MRI and histologic analysis showed no difference in comparison to control groups, but the authors’ conclusion proposed that the number of stem cells injected might have been too minimal to show a clinical effect.

Other Applications

Although outside the scope of this article, stem cells have demonstrated efficacy in the treatment of a number of osseous clinical entities. This includes the treatment of fracture nonunion, augmentation of spinal fusion, and assistance in the treatment of osteonecrosis.⁸⁴

Summary

As a scientific community, our understanding of the use of stem cells, their nuances, and their indications has expanded dramatically over the last several years. Stem cell treatment has particularly infiltrated the world of operative and nonoperative sports medicine, given in part the active patient population seeking greater levels of improvement.⁸⁵ Stem cell therapy offers a potentially effective therapy for a multitude of pathologies because of these cells’ anti-inflammatory, immunoregulatory, angiogenic, and paracrine effects.⁸⁶ It thus remains a very dynamic option in the study of musculoskeletal tissue regeneration. While the potential exists for stem cell use in daily surgery practices, it is still premature to predict whether this can be expected.

The ideal stem cell sources (including allogeneic or autologous), preparation, cell number, timing, and means of application continue to be evaluated, as well as those advantageous pathologies that can benefit from the technology. In order to better answer these pertinent questions, we need to make sure we have a safe, economic, and ethically acceptable means for stem cell translational research efforts. More high-level studies with standardized protocols need to be performed. It is necessary to improve national and international collaboration in research, as well as collaboration with governing bodies, to attempt to further scientific advancement in this field of research.⁴⁹ Further study on embryonic stem cell use may be valuable as well, pending governmental approval. Finally, more dedicated research efforts must be placed on the utility of adjuncts with stem cell use, including PRP and scaffolds, which may increase protection, nutritional support, and mechanical stimulation of the administered stem cells.

Reverse total shoulder arthroplasty (RTSA) has become a reliable treatment option for many pathologic conditions of the shoulder, including rotator cuff arthropathy, proximal humerus fractures, and others.^1-4 While the treatment outcomes have generally been reported as good, some concern exists over the postoperative range of motion (ROM) in patients following RTSA, including external rotation.^5-7 The original RTSA design was introduced by Neer in the 1970s and has undergone many modifications since that time.^1,2 The original Grammont-style prosthesis involved medialization of the glenoid, inferiorizing the center of rotation (with increased deltoid tensioning), and a neck-shaft angle of 155°.^1,8 While clinical results of the 155° design were encouraging, concerns arose over the significance of the common finding of scapular notching, or contact between the scapular neck and inferior portion of the humeral polyethylene when the arm is adducted.^9,10

To address this concern, a prosthesis design with a 135° neck-shaft angle was introduced.¹¹ This new design did significantly decrease the rate of scapular notching, and although some reported a concern over implant stability with the 135° prosthesis, recent data has shown no difference in dislocation rates between the 135° and 155° prostheses.³ A different variable that has not been evaluated between these prostheses is the active ROM that is achieved postoperatively, and the change in ROM from pre- to post-RTSA.^12,13 As active ROM plays a significant role in shoulder function and patient satisfaction, the question of whether a significant difference exists in postoperative ROM between the 135° and 155° prostheses must be addressed.

The purpose of this study was to perform a systematic review investigating active ROM following RTSA to determine if active postoperative ROM following RTSA differs between the 135° and 155° humeral inclination prostheses, and to determine if there is a significant difference between the change in preoperative and postoperative ROM between the 135° and 155° prostheses. The authors hypothesize that there will be no significant difference in active postoperative ROM between the 135° and 155° prostheses, and that the difference between preoperative and postoperative ROM (that is, the amount of motion gained by the surgery) will not significantly differ between the 135° and 155° prostheses.

Methods

A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PRISMA checklist.¹⁵ Systematic review registration was performed using the PROSPERO international prospective register of systematic reviews (registration date 3/9/15, registration number CRD42015017367).¹⁶ Two reviewers independently conducted the search on March 7, 2015 using the following databases: Medline, Cochrane Central Register of Controlled Trials, SportDiscus, and CINAHL. The electronic search citation algorithm utilized was: (((((reverse[Title/Abstract]) AND shoulder[Title/Abstract]) AND arthroplasty[Title/Abstract]) NOT arthroscopic[Title/Abstract]) NOT cadaver[Title/Abstract]) NOT biomechanical[Title/Abstract]. English language Level I-IV evidence (2011 update by the Oxford Centre for Evidence-Based Medicine¹⁷) clinical studies that reported the type of RTSA prosthesis that was used as well as postoperative ROM with at least 12 months follow-up were eligible. All references within included studies were cross-referenced for inclusion if missed by the initial search. If duplicate subject publications were discovered, the study with the longer duration of follow-up or larger number of patients was included. Level V evidence reviews, letters to the editor, basic science, biomechanical studies, arthroscopic shoulder surgery, imaging, surgical technique, and classification studies were excluded. Studies were excluded if both a 135° and 155° prosthesis were utilized and the outcomes were not stratified by the humeral inclination. Studies that did not report ROM were excluded.

A total of 456 studies were located, and, after implementation of the exclusion criteria, 65 studies from 2005-2015 were included in the final analysis (Figure). Subjects of interest in this systematic review underwent a RTSA. Studies were not excluded based on the surgical indications (rotator cuff tear arthropathy, proximal humerus fractures, osteoarthritis) and there was no minimum follow-up or rehabilitation requirement. Study and subject demographic parameters analyzed included year of publication, journal of publication, country and continent of publication, years of subject enrollment, presence of study financial conflict of interest, number of subjects and shoulders, gender, age, the manufacturer and type of prosthesis used, and the degree of the humeral inclination (135° vs 155° humeral cup). Preoperative ROM, including forward elevation, abduction, external rotation with the arm adducted, and external rotation with the arm at 90° of abduction, were recorded. The same ROM measurements were recorded for the final follow-up visit that was reported. Internal rotation was recorded, but because of the variability with how this measurement was reported, it was not analyzed. Clinical outcome scores and complications were not assessed. Study methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS).¹⁸

Statistical Analysis

Descriptive statistics were calculated, including mean ± standard deviation for quantitative continuous data and frequencies with percentages for qualitative categorical data. ROM comparisons between 135° and 155° components (pre- vs postoperative for each and postoperative between the 2) were made using 2 proportion z-test calculator (http://in-silico.net/tools/statistics/ztest) using alpha .05 because of the difference in sample sizes between compared groups.

Results

Sixty-five studies with 3302 patients (3434 shoulders) were included in this study. There was a total of 1211 shoulders in the 135° lateralized glenosphere group and 2223 shoulders in the 155° group. The studies had an average MCMS of 40.4 ± 8.2 (poor), 48% of studies reported a conflict of interest, 32% had no conflict of interest, and 20% did not report whether a conflict of interest existed or not. The majority of studies included were level IV evidence (85%). Mean patient age was 71.1 ± 7.6 years; 29% of patients were male and 71% were female. No significant difference existed between patient age at the time of surgery; the average age of patients in the 135° lateralized glenosphere group was 71.67 ± 3.8 years, while the average patient age of patients in the 155° group was 70.97 ± 8.8 years. Mean follow-up for all patients included in this study was 37.2 ± 16.5 months. Of the 65 studies included, 3 were published from Asia, 4 were published from Australia, 24 were from North America, and 34 were from Europe. Of the individual countries whose studies were included, the United States had 23 included studies, France had 13 included studies, and Italy had 4 included studies. All other countries had <4 studies included.

Patients who received either a 135° or a 155° prosthesis showed significant improvements in external rotation with the arm at the side (P < .05), forward elevation (P < .05), and abduction (P < .05) following surgery (Table). When comparing the 135° and 155° groups, patients who received a 135° prosthesis showed significantly greater improvements in external rotation with the arm at the side (P < .001) and had significantly more overall external rotation postoperatively (P < .001) than patients who received a 155° prosthesis. The only preoperative ROM difference between groups was the 155° group started with significantly more forward elevation than the 135°group prior to surgery (P = .002).

Discussion

RTSA is indicated in patients with rotator cuff tear arthropathy, pseudoparalysis, and a functional deltoid.^1,2,4 The purpose of this systematic review was to determine if active ROM following RTSA differs between the 135° and 155° humeral inclination prostheses, and to determine if there is a significant difference between the change in preoperative and postoperative ROM between the 135° and 155° prostheses. Forward elevation, abduction, and external rotation all significantly improved following surgery in both groups, with no significant difference between groups in motion or amount of motion improvement, mostly confirming the study hypotheses. However, patients in the 135° group had significantly greater postoperative external rotation and greater amount of external rotation improvement compared to the 155° group.

Two of the frequently debated issues regarding implant geometry is stability and scapular notching between the 135° and 155° humeral inclination designs. Erickson and colleagues3 recently evaluated the rate of scapular notching and dislocations between the 135° and 155° RTSA prostheses. The authors found that the 135° prosthesis had a significantly lower incidence of scapular notching vs the 155° group and that the rate of dislocations was not significantly different between groups.³ In the latter systematic review, the authors attempted to evaluate ROM between the 135° and 155° prostheses, but as the inclusion criteria of the study was reporting on scapular notching and dislocation rates, many studies reporting solely on ROM were excluded, and the influence of humeral inclination on ROM was inconclusive.³ Furthermore, there have been no studies that have directly compared ROM following RTSA between the 135° and 155° prostheses. While studies evaluating each prosthesis on an individual level have shown an improvement in ROM from pre- to postsurgery, there have been no large studies that have compared the postoperative ROM and change in pre- to postoperative ROM between the 135° and 155° prostheses.^11,13,19,20

One study by Valenti and colleagues²¹ evaluated a group of 30 patients with an average age of 69.5 years who underwent RTSA using either a 135° or a 155° prosthesis. Although the study did not directly compare the 2 types of prostheses, it did report the separate outcomes for each prosthesis. At an average follow-up of 36.4 months, the authors found that patients who had the 135° prosthesis implanted had a mean increase in forward elevation and external rotation of 53° and 9°, while patients who had the 155° showed an increase of 56° in forward elevation and a loss of 1° of external rotation. Both prostheses showed a significant increase in forward elevation, but neither had a significant increase in external rotation. Furthermore, scapular notching was seen in 4 patients in the 155° group, while no patients in the 135° group had evidence of notching.

The results of the current study were similar in that both the 135° and 155° prosthesis showed improvements in forward elevation following surgery, and the 135° group showed a significantly greater gain in external rotation than the 155° group. A significant component of shoulder function and patient satisfaction following RTSA is active ROM. However, this variable has not explicitly been evaluated in the literature until now. The clinical significance of this finding is unclear. Patients with adequate external rotation prior to surgery likely would not see a functional difference between prostheses, while those patients who were borderline on a functional amount of external rotation would see a clinically significant benefit with the 135° prosthesis. Studies have shown that the 135° prosthesis is more anatomic than the 155°, and this could explain the difference seen in ROM outcomes between the 2 prostheses.¹⁹ Ladermann and colleagues²² recently created and evaluated a 3-dimensional computer model to evaluate possible differences between the 135° and 155° prosthesis. The authors found a significant increase in external rotation of the 135° compared to the 155°, likely related to a difference in acromiohumeral distance as well as inlay vs onlay humeral trays between the 2 prostheses. The results of this study parallel the computer model, thereby validating these experimental results.

It is important to understand what the minimum functional ROM of the shoulder is (in other words, the ROM necessary to complete activities of daily living (ADLs).²³ Namdari and colleagues²⁴ used motion analysis software to evaluate the shoulder ROM necessary to complete 10 different ADLs, including combing hair, washing the back of the opposite shoulder, and reaching a shelf above their head without bending their elbow in 20 patients with a mean age of 29.2 years. They found that patients required 121° ± 6.7° of flexion, 46° ± 5.3° of extension, 128° ± 7.9° of abduction, 116° ± 9.1° of cross-body adduction, 59° ± 10° of external rotation with the arm 90° abducted, and 102° ± 7.7° of internal rotation with the arm at the side (external rotation with the arm at the side was not well defined).²⁴ Hence, while abduction and forward elevation seem comparable, the results from the current study do raise concerns about the amount of external rotation obtained following RTSA as it relates to a patients’ ability to perform ADLs, specifically in the 155° prosthesis, as the average postoperative external rotation in this group was 20.5°. Therefore, based on the results of this study, it appears that, while both the 135° and 155° RTSA prostheses provide similar gain in forward elevation and abduction ROM as well as overall forward elevation and abduction, the 135° prosthesis provides significantly more external rotation with the arm at the side than the 155° prosthesis.

Limitations

Although this study attempted to look at all studies that reported active ROM in patients following a RTSA, and 2 authors performed the search, there is a possibility that some studies were missed, introducing study selection bias. Furthermore, the mean follow-up was over 3 years following surgery, but the minimum follow-up requirement for studies to be included was only 12 months. Hence, this transfer bias introduces the possibility that the patient’s ROM would have changed had they been followed for a standard period of time. There are many variables that come into play in evaluating ROM, and although the study attempted to control for these, there are some that could not be controlled for due to lack of reporting by some studies. Glenosphere size and humeral retroversion were not recorded, as they were not reliably reported in all studies, so motion outcomes based on these variables was not evaluated. Complications and clinical outcomes were not assessed in this review and as such, conclusions regarding these variables cannot be drawn from this study. Finally, indications for surgery were not reliably reported in the studies included in this paper, so differences may have existed between surgical indications of the 135° and 155° groups that could have affected outcomes.

Conclusion

Patients who receive a 135° RTSA gain significantly more external rotation from pre- to postsurgery and have an overall greater amount of external rotation than patients who receive a 155° prosthesis. Both groups show improvements in forward elevation, external rotation, and abduction following surgery.

Reverse total shoulder arthroplasty (RTSA) has become a reliable treatment option for many pathologic conditions of the shoulder, including rotator cuff arthropathy, proximal humerus fractures, and others.^1-4 While the treatment outcomes have generally been reported as good, some concern exists over the postoperative range of motion (ROM) in patients following RTSA, including external rotation.^5-7 The original RTSA design was introduced by Neer in the 1970s and has undergone many modifications since that time.^1,2 The original Grammont-style prosthesis involved medialization of the glenoid, inferiorizing the center of rotation (with increased deltoid tensioning), and a neck-shaft angle of 155°.^1,8 While clinical results of the 155° design were encouraging, concerns arose over the significance of the common finding of scapular notching, or contact between the scapular neck and inferior portion of the humeral polyethylene when the arm is adducted.^9,10

To address this concern, a prosthesis design with a 135° neck-shaft angle was introduced.¹¹ This new design did significantly decrease the rate of scapular notching, and although some reported a concern over implant stability with the 135° prosthesis, recent data has shown no difference in dislocation rates between the 135° and 155° prostheses.³ A different variable that has not been evaluated between these prostheses is the active ROM that is achieved postoperatively, and the change in ROM from pre- to post-RTSA.^12,13 As active ROM plays a significant role in shoulder function and patient satisfaction, the question of whether a significant difference exists in postoperative ROM between the 135° and 155° prostheses must be addressed.

The purpose of this study was to perform a systematic review investigating active ROM following RTSA to determine if active postoperative ROM following RTSA differs between the 135° and 155° humeral inclination prostheses, and to determine if there is a significant difference between the change in preoperative and postoperative ROM between the 135° and 155° prostheses. The authors hypothesize that there will be no significant difference in active postoperative ROM between the 135° and 155° prostheses, and that the difference between preoperative and postoperative ROM (that is, the amount of motion gained by the surgery) will not significantly differ between the 135° and 155° prostheses.

Methods

A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PRISMA checklist.¹⁵ Systematic review registration was performed using the PROSPERO international prospective register of systematic reviews (registration date 3/9/15, registration number CRD42015017367).¹⁶ Two reviewers independently conducted the search on March 7, 2015 using the following databases: Medline, Cochrane Central Register of Controlled Trials, SportDiscus, and CINAHL. The electronic search citation algorithm utilized was: (((((reverse[Title/Abstract]) AND shoulder[Title/Abstract]) AND arthroplasty[Title/Abstract]) NOT arthroscopic[Title/Abstract]) NOT cadaver[Title/Abstract]) NOT biomechanical[Title/Abstract]. English language Level I-IV evidence (2011 update by the Oxford Centre for Evidence-Based Medicine¹⁷) clinical studies that reported the type of RTSA prosthesis that was used as well as postoperative ROM with at least 12 months follow-up were eligible. All references within included studies were cross-referenced for inclusion if missed by the initial search. If duplicate subject publications were discovered, the study with the longer duration of follow-up or larger number of patients was included. Level V evidence reviews, letters to the editor, basic science, biomechanical studies, arthroscopic shoulder surgery, imaging, surgical technique, and classification studies were excluded. Studies were excluded if both a 135° and 155° prosthesis were utilized and the outcomes were not stratified by the humeral inclination. Studies that did not report ROM were excluded.

A total of 456 studies were located, and, after implementation of the exclusion criteria, 65 studies from 2005-2015 were included in the final analysis (Figure). Subjects of interest in this systematic review underwent a RTSA. Studies were not excluded based on the surgical indications (rotator cuff tear arthropathy, proximal humerus fractures, osteoarthritis) and there was no minimum follow-up or rehabilitation requirement. Study and subject demographic parameters analyzed included year of publication, journal of publication, country and continent of publication, years of subject enrollment, presence of study financial conflict of interest, number of subjects and shoulders, gender, age, the manufacturer and type of prosthesis used, and the degree of the humeral inclination (135° vs 155° humeral cup). Preoperative ROM, including forward elevation, abduction, external rotation with the arm adducted, and external rotation with the arm at 90° of abduction, were recorded. The same ROM measurements were recorded for the final follow-up visit that was reported. Internal rotation was recorded, but because of the variability with how this measurement was reported, it was not analyzed. Clinical outcome scores and complications were not assessed. Study methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS).¹⁸

Statistical Analysis

Descriptive statistics were calculated, including mean ± standard deviation for quantitative continuous data and frequencies with percentages for qualitative categorical data. ROM comparisons between 135° and 155° components (pre- vs postoperative for each and postoperative between the 2) were made using 2 proportion z-test calculator (http://in-silico.net/tools/statistics/ztest) using alpha .05 because of the difference in sample sizes between compared groups.

Results

Sixty-five studies with 3302 patients (3434 shoulders) were included in this study. There was a total of 1211 shoulders in the 135° lateralized glenosphere group and 2223 shoulders in the 155° group. The studies had an average MCMS of 40.4 ± 8.2 (poor), 48% of studies reported a conflict of interest, 32% had no conflict of interest, and 20% did not report whether a conflict of interest existed or not. The majority of studies included were level IV evidence (85%). Mean patient age was 71.1 ± 7.6 years; 29% of patients were male and 71% were female. No significant difference existed between patient age at the time of surgery; the average age of patients in the 135° lateralized glenosphere group was 71.67 ± 3.8 years, while the average patient age of patients in the 155° group was 70.97 ± 8.8 years. Mean follow-up for all patients included in this study was 37.2 ± 16.5 months. Of the 65 studies included, 3 were published from Asia, 4 were published from Australia, 24 were from North America, and 34 were from Europe. Of the individual countries whose studies were included, the United States had 23 included studies, France had 13 included studies, and Italy had 4 included studies. All other countries had <4 studies included.

Patients who received either a 135° or a 155° prosthesis showed significant improvements in external rotation with the arm at the side (P < .05), forward elevation (P < .05), and abduction (P < .05) following surgery (Table). When comparing the 135° and 155° groups, patients who received a 135° prosthesis showed significantly greater improvements in external rotation with the arm at the side (P < .001) and had significantly more overall external rotation postoperatively (P < .001) than patients who received a 155° prosthesis. The only preoperative ROM difference between groups was the 155° group started with significantly more forward elevation than the 135°group prior to surgery (P = .002).

Discussion

RTSA is indicated in patients with rotator cuff tear arthropathy, pseudoparalysis, and a functional deltoid.^1,2,4 The purpose of this systematic review was to determine if active ROM following RTSA differs between the 135° and 155° humeral inclination prostheses, and to determine if there is a significant difference between the change in preoperative and postoperative ROM between the 135° and 155° prostheses. Forward elevation, abduction, and external rotation all significantly improved following surgery in both groups, with no significant difference between groups in motion or amount of motion improvement, mostly confirming the study hypotheses. However, patients in the 135° group had significantly greater postoperative external rotation and greater amount of external rotation improvement compared to the 155° group.

Two of the frequently debated issues regarding implant geometry is stability and scapular notching between the 135° and 155° humeral inclination designs. Erickson and colleagues3 recently evaluated the rate of scapular notching and dislocations between the 135° and 155° RTSA prostheses. The authors found that the 135° prosthesis had a significantly lower incidence of scapular notching vs the 155° group and that the rate of dislocations was not significantly different between groups.³ In the latter systematic review, the authors attempted to evaluate ROM between the 135° and 155° prostheses, but as the inclusion criteria of the study was reporting on scapular notching and dislocation rates, many studies reporting solely on ROM were excluded, and the influence of humeral inclination on ROM was inconclusive.³ Furthermore, there have been no studies that have directly compared ROM following RTSA between the 135° and 155° prostheses. While studies evaluating each prosthesis on an individual level have shown an improvement in ROM from pre- to postsurgery, there have been no large studies that have compared the postoperative ROM and change in pre- to postoperative ROM between the 135° and 155° prostheses.^11,13,19,20

One study by Valenti and colleagues²¹ evaluated a group of 30 patients with an average age of 69.5 years who underwent RTSA using either a 135° or a 155° prosthesis. Although the study did not directly compare the 2 types of prostheses, it did report the separate outcomes for each prosthesis. At an average follow-up of 36.4 months, the authors found that patients who had the 135° prosthesis implanted had a mean increase in forward elevation and external rotation of 53° and 9°, while patients who had the 155° showed an increase of 56° in forward elevation and a loss of 1° of external rotation. Both prostheses showed a significant increase in forward elevation, but neither had a significant increase in external rotation. Furthermore, scapular notching was seen in 4 patients in the 155° group, while no patients in the 135° group had evidence of notching.

The results of the current study were similar in that both the 135° and 155° prosthesis showed improvements in forward elevation following surgery, and the 135° group showed a significantly greater gain in external rotation than the 155° group. A significant component of shoulder function and patient satisfaction following RTSA is active ROM. However, this variable has not explicitly been evaluated in the literature until now. The clinical significance of this finding is unclear. Patients with adequate external rotation prior to surgery likely would not see a functional difference between prostheses, while those patients who were borderline on a functional amount of external rotation would see a clinically significant benefit with the 135° prosthesis. Studies have shown that the 135° prosthesis is more anatomic than the 155°, and this could explain the difference seen in ROM outcomes between the 2 prostheses.¹⁹ Ladermann and colleagues²² recently created and evaluated a 3-dimensional computer model to evaluate possible differences between the 135° and 155° prosthesis. The authors found a significant increase in external rotation of the 135° compared to the 155°, likely related to a difference in acromiohumeral distance as well as inlay vs onlay humeral trays between the 2 prostheses. The results of this study parallel the computer model, thereby validating these experimental results.

It is important to understand what the minimum functional ROM of the shoulder is (in other words, the ROM necessary to complete activities of daily living (ADLs).²³ Namdari and colleagues²⁴ used motion analysis software to evaluate the shoulder ROM necessary to complete 10 different ADLs, including combing hair, washing the back of the opposite shoulder, and reaching a shelf above their head without bending their elbow in 20 patients with a mean age of 29.2 years. They found that patients required 121° ± 6.7° of flexion, 46° ± 5.3° of extension, 128° ± 7.9° of abduction, 116° ± 9.1° of cross-body adduction, 59° ± 10° of external rotation with the arm 90° abducted, and 102° ± 7.7° of internal rotation with the arm at the side (external rotation with the arm at the side was not well defined).²⁴ Hence, while abduction and forward elevation seem comparable, the results from the current study do raise concerns about the amount of external rotation obtained following RTSA as it relates to a patients’ ability to perform ADLs, specifically in the 155° prosthesis, as the average postoperative external rotation in this group was 20.5°. Therefore, based on the results of this study, it appears that, while both the 135° and 155° RTSA prostheses provide similar gain in forward elevation and abduction ROM as well as overall forward elevation and abduction, the 135° prosthesis provides significantly more external rotation with the arm at the side than the 155° prosthesis.

Limitations

Although this study attempted to look at all studies that reported active ROM in patients following a RTSA, and 2 authors performed the search, there is a possibility that some studies were missed, introducing study selection bias. Furthermore, the mean follow-up was over 3 years following surgery, but the minimum follow-up requirement for studies to be included was only 12 months. Hence, this transfer bias introduces the possibility that the patient’s ROM would have changed had they been followed for a standard period of time. There are many variables that come into play in evaluating ROM, and although the study attempted to control for these, there are some that could not be controlled for due to lack of reporting by some studies. Glenosphere size and humeral retroversion were not recorded, as they were not reliably reported in all studies, so motion outcomes based on these variables was not evaluated. Complications and clinical outcomes were not assessed in this review and as such, conclusions regarding these variables cannot be drawn from this study. Finally, indications for surgery were not reliably reported in the studies included in this paper, so differences may have existed between surgical indications of the 135° and 155° groups that could have affected outcomes.

Conclusion

Patients who receive a 135° RTSA gain significantly more external rotation from pre- to postsurgery and have an overall greater amount of external rotation than patients who receive a 155° prosthesis. Both groups show improvements in forward elevation, external rotation, and abduction following surgery.

Reverse total shoulder arthroplasty (RTSA) has become a reliable treatment option for many pathologic conditions of the shoulder, including rotator cuff arthropathy, proximal humerus fractures, and others.^1-4 While the treatment outcomes have generally been reported as good, some concern exists over the postoperative range of motion (ROM) in patients following RTSA, including external rotation.^5-7 The original RTSA design was introduced by Neer in the 1970s and has undergone many modifications since that time.^1,2 The original Grammont-style prosthesis involved medialization of the glenoid, inferiorizing the center of rotation (with increased deltoid tensioning), and a neck-shaft angle of 155°.^1,8 While clinical results of the 155° design were encouraging, concerns arose over the significance of the common finding of scapular notching, or contact between the scapular neck and inferior portion of the humeral polyethylene when the arm is adducted.^9,10

To address this concern, a prosthesis design with a 135° neck-shaft angle was introduced.¹¹ This new design did significantly decrease the rate of scapular notching, and although some reported a concern over implant stability with the 135° prosthesis, recent data has shown no difference in dislocation rates between the 135° and 155° prostheses.³ A different variable that has not been evaluated between these prostheses is the active ROM that is achieved postoperatively, and the change in ROM from pre- to post-RTSA.^12,13 As active ROM plays a significant role in shoulder function and patient satisfaction, the question of whether a significant difference exists in postoperative ROM between the 135° and 155° prostheses must be addressed.

The purpose of this study was to perform a systematic review investigating active ROM following RTSA to determine if active postoperative ROM following RTSA differs between the 135° and 155° humeral inclination prostheses, and to determine if there is a significant difference between the change in preoperative and postoperative ROM between the 135° and 155° prostheses. The authors hypothesize that there will be no significant difference in active postoperative ROM between the 135° and 155° prostheses, and that the difference between preoperative and postoperative ROM (that is, the amount of motion gained by the surgery) will not significantly differ between the 135° and 155° prostheses.

Methods

A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PRISMA checklist.¹⁵ Systematic review registration was performed using the PROSPERO international prospective register of systematic reviews (registration date 3/9/15, registration number CRD42015017367).¹⁶ Two reviewers independently conducted the search on March 7, 2015 using the following databases: Medline, Cochrane Central Register of Controlled Trials, SportDiscus, and CINAHL. The electronic search citation algorithm utilized was: (((((reverse[Title/Abstract]) AND shoulder[Title/Abstract]) AND arthroplasty[Title/Abstract]) NOT arthroscopic[Title/Abstract]) NOT cadaver[Title/Abstract]) NOT biomechanical[Title/Abstract]. English language Level I-IV evidence (2011 update by the Oxford Centre for Evidence-Based Medicine¹⁷) clinical studies that reported the type of RTSA prosthesis that was used as well as postoperative ROM with at least 12 months follow-up were eligible. All references within included studies were cross-referenced for inclusion if missed by the initial search. If duplicate subject publications were discovered, the study with the longer duration of follow-up or larger number of patients was included. Level V evidence reviews, letters to the editor, basic science, biomechanical studies, arthroscopic shoulder surgery, imaging, surgical technique, and classification studies were excluded. Studies were excluded if both a 135° and 155° prosthesis were utilized and the outcomes were not stratified by the humeral inclination. Studies that did not report ROM were excluded.

A total of 456 studies were located, and, after implementation of the exclusion criteria, 65 studies from 2005-2015 were included in the final analysis (Figure). Subjects of interest in this systematic review underwent a RTSA. Studies were not excluded based on the surgical indications (rotator cuff tear arthropathy, proximal humerus fractures, osteoarthritis) and there was no minimum follow-up or rehabilitation requirement. Study and subject demographic parameters analyzed included year of publication, journal of publication, country and continent of publication, years of subject enrollment, presence of study financial conflict of interest, number of subjects and shoulders, gender, age, the manufacturer and type of prosthesis used, and the degree of the humeral inclination (135° vs 155° humeral cup). Preoperative ROM, including forward elevation, abduction, external rotation with the arm adducted, and external rotation with the arm at 90° of abduction, were recorded. The same ROM measurements were recorded for the final follow-up visit that was reported. Internal rotation was recorded, but because of the variability with how this measurement was reported, it was not analyzed. Clinical outcome scores and complications were not assessed. Study methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS).¹⁸

Statistical Analysis

Descriptive statistics were calculated, including mean ± standard deviation for quantitative continuous data and frequencies with percentages for qualitative categorical data. ROM comparisons between 135° and 155° components (pre- vs postoperative for each and postoperative between the 2) were made using 2 proportion z-test calculator (http://in-silico.net/tools/statistics/ztest) using alpha .05 because of the difference in sample sizes between compared groups.

Results

Sixty-five studies with 3302 patients (3434 shoulders) were included in this study. There was a total of 1211 shoulders in the 135° lateralized glenosphere group and 2223 shoulders in the 155° group. The studies had an average MCMS of 40.4 ± 8.2 (poor), 48% of studies reported a conflict of interest, 32% had no conflict of interest, and 20% did not report whether a conflict of interest existed or not. The majority of studies included were level IV evidence (85%). Mean patient age was 71.1 ± 7.6 years; 29% of patients were male and 71% were female. No significant difference existed between patient age at the time of surgery; the average age of patients in the 135° lateralized glenosphere group was 71.67 ± 3.8 years, while the average patient age of patients in the 155° group was 70.97 ± 8.8 years. Mean follow-up for all patients included in this study was 37.2 ± 16.5 months. Of the 65 studies included, 3 were published from Asia, 4 were published from Australia, 24 were from North America, and 34 were from Europe. Of the individual countries whose studies were included, the United States had 23 included studies, France had 13 included studies, and Italy had 4 included studies. All other countries had <4 studies included.

Patients who received either a 135° or a 155° prosthesis showed significant improvements in external rotation with the arm at the side (P < .05), forward elevation (P < .05), and abduction (P < .05) following surgery (Table). When comparing the 135° and 155° groups, patients who received a 135° prosthesis showed significantly greater improvements in external rotation with the arm at the side (P < .001) and had significantly more overall external rotation postoperatively (P < .001) than patients who received a 155° prosthesis. The only preoperative ROM difference between groups was the 155° group started with significantly more forward elevation than the 135°group prior to surgery (P = .002).

Discussion

RTSA is indicated in patients with rotator cuff tear arthropathy, pseudoparalysis, and a functional deltoid.^1,2,4 The purpose of this systematic review was to determine if active ROM following RTSA differs between the 135° and 155° humeral inclination prostheses, and to determine if there is a significant difference between the change in preoperative and postoperative ROM between the 135° and 155° prostheses. Forward elevation, abduction, and external rotation all significantly improved following surgery in both groups, with no significant difference between groups in motion or amount of motion improvement, mostly confirming the study hypotheses. However, patients in the 135° group had significantly greater postoperative external rotation and greater amount of external rotation improvement compared to the 155° group.

Two of the frequently debated issues regarding implant geometry is stability and scapular notching between the 135° and 155° humeral inclination designs. Erickson and colleagues3 recently evaluated the rate of scapular notching and dislocations between the 135° and 155° RTSA prostheses. The authors found that the 135° prosthesis had a significantly lower incidence of scapular notching vs the 155° group and that the rate of dislocations was not significantly different between groups.³ In the latter systematic review, the authors attempted to evaluate ROM between the 135° and 155° prostheses, but as the inclusion criteria of the study was reporting on scapular notching and dislocation rates, many studies reporting solely on ROM were excluded, and the influence of humeral inclination on ROM was inconclusive.³ Furthermore, there have been no studies that have directly compared ROM following RTSA between the 135° and 155° prostheses. While studies evaluating each prosthesis on an individual level have shown an improvement in ROM from pre- to postsurgery, there have been no large studies that have compared the postoperative ROM and change in pre- to postoperative ROM between the 135° and 155° prostheses.^11,13,19,20

One study by Valenti and colleagues²¹ evaluated a group of 30 patients with an average age of 69.5 years who underwent RTSA using either a 135° or a 155° prosthesis. Although the study did not directly compare the 2 types of prostheses, it did report the separate outcomes for each prosthesis. At an average follow-up of 36.4 months, the authors found that patients who had the 135° prosthesis implanted had a mean increase in forward elevation and external rotation of 53° and 9°, while patients who had the 155° showed an increase of 56° in forward elevation and a loss of 1° of external rotation. Both prostheses showed a significant increase in forward elevation, but neither had a significant increase in external rotation. Furthermore, scapular notching was seen in 4 patients in the 155° group, while no patients in the 135° group had evidence of notching.

The results of the current study were similar in that both the 135° and 155° prosthesis showed improvements in forward elevation following surgery, and the 135° group showed a significantly greater gain in external rotation than the 155° group. A significant component of shoulder function and patient satisfaction following RTSA is active ROM. However, this variable has not explicitly been evaluated in the literature until now. The clinical significance of this finding is unclear. Patients with adequate external rotation prior to surgery likely would not see a functional difference between prostheses, while those patients who were borderline on a functional amount of external rotation would see a clinically significant benefit with the 135° prosthesis. Studies have shown that the 135° prosthesis is more anatomic than the 155°, and this could explain the difference seen in ROM outcomes between the 2 prostheses.¹⁹ Ladermann and colleagues²² recently created and evaluated a 3-dimensional computer model to evaluate possible differences between the 135° and 155° prosthesis. The authors found a significant increase in external rotation of the 135° compared to the 155°, likely related to a difference in acromiohumeral distance as well as inlay vs onlay humeral trays between the 2 prostheses. The results of this study parallel the computer model, thereby validating these experimental results.

It is important to understand what the minimum functional ROM of the shoulder is (in other words, the ROM necessary to complete activities of daily living (ADLs).²³ Namdari and colleagues²⁴ used motion analysis software to evaluate the shoulder ROM necessary to complete 10 different ADLs, including combing hair, washing the back of the opposite shoulder, and reaching a shelf above their head without bending their elbow in 20 patients with a mean age of 29.2 years. They found that patients required 121° ± 6.7° of flexion, 46° ± 5.3° of extension, 128° ± 7.9° of abduction, 116° ± 9.1° of cross-body adduction, 59° ± 10° of external rotation with the arm 90° abducted, and 102° ± 7.7° of internal rotation with the arm at the side (external rotation with the arm at the side was not well defined).²⁴ Hence, while abduction and forward elevation seem comparable, the results from the current study do raise concerns about the amount of external rotation obtained following RTSA as it relates to a patients’ ability to perform ADLs, specifically in the 155° prosthesis, as the average postoperative external rotation in this group was 20.5°. Therefore, based on the results of this study, it appears that, while both the 135° and 155° RTSA prostheses provide similar gain in forward elevation and abduction ROM as well as overall forward elevation and abduction, the 135° prosthesis provides significantly more external rotation with the arm at the side than the 155° prosthesis.

Limitations

Although this study attempted to look at all studies that reported active ROM in patients following a RTSA, and 2 authors performed the search, there is a possibility that some studies were missed, introducing study selection bias. Furthermore, the mean follow-up was over 3 years following surgery, but the minimum follow-up requirement for studies to be included was only 12 months. Hence, this transfer bias introduces the possibility that the patient’s ROM would have changed had they been followed for a standard period of time. There are many variables that come into play in evaluating ROM, and although the study attempted to control for these, there are some that could not be controlled for due to lack of reporting by some studies. Glenosphere size and humeral retroversion were not recorded, as they were not reliably reported in all studies, so motion outcomes based on these variables was not evaluated. Complications and clinical outcomes were not assessed in this review and as such, conclusions regarding these variables cannot be drawn from this study. Finally, indications for surgery were not reliably reported in the studies included in this paper, so differences may have existed between surgical indications of the 135° and 155° groups that could have affected outcomes.

Conclusion

Patients who receive a 135° RTSA gain significantly more external rotation from pre- to postsurgery and have an overall greater amount of external rotation than patients who receive a 155° prosthesis. Both groups show improvements in forward elevation, external rotation, and abduction following surgery.

Shoulder arthroplasty (SA), including total SA (TSA) and reverse TSA, is an effective surgical treatment for fracture and primary or secondary degenerative disease of the shoulder.¹ Over the past few decades, use of SA has increased dramatically, from about 5000 cases in 1990 to 7000 in 2000 and more than 26,000 in 2008.^1,2

Complications associated with SA generally are classified as perioperative (occurring during the operative index) or long-term (postdischarge).³ Long-term complications include implant loosening, instability, revision, infection, rotator cuff tear, neural injury, and deltoid detachment.^1,4,5 Perioperative complications, which are less commonly reported, include intraoperative fracture, infection, neural injury, venous thromboembolic events (VTEs, including pulmonary embolism [PE] and deep vein thrombosis [DVT]), transfusion, and death.^3,6-10

SA is an attractive treatment option for patients with rheumatoid arthritis (RA), as the effects of pain on these patients are greater in the shoulder joint than in any other joint.¹¹ Patients with RA pose unique orthopedic surgical challenges, including any combination of decreased bone mineralization, poor capsular tissue integrity, and osteonecrosis.^3,12 In addition, RA patients may be taking immunosuppressive medications that have severe side effects, and they may require multiple surgeries.^12,13 These factors predispose patients with RA to complications that include infection and wound dehiscence.^3,5,12-14

The complex nature of RA has prompted investigators to examine outcome measures in this patient group. Hambright and colleagues³ used the Nationwide Inpatient Sample (NIS) to examine perioperative outcomes in RA patients who underwent TSA between 1988 and 2005.³ They found that TSA patients with RA had shorter and less costly hospital stays and were more likely to have a routine discharge.³ Using the same patient population drawn from the period 2006–2011, we conducted a study to determine if this unexpected trend persists as the number of TSAs and quality of postoperative care continue to increase. Given the potential for anemia of chronic disease and the systemic inflammatory nature of RA, we hypothesized that the perioperative complication profile of RA patients would be worse than that of non-RA patients.

Materials and Methods

NIS data were acquired for the period 2006–2011. The NIS is the largest publicly available all-payer inpatient database, with a random 20% sample of about 1000 US hospitals accounting for 7 to 8 million inpatient stays. The database supplies weights used to estimate national totals, at about 35 million inpatient visits per year. NIS inpatient data are limited to the operative index. Postdischarge information is not available. The NIS is managed by the Healthcare Cost and Utilization Project, which is sponsored by the Agency for Healthcare Research and Quality. The quality of NIS data is assessed and validated by an independent contractor. NIS data have been widely used to examine perioperative outcomes.^15-17

NIS data cover patient and hospital demographics, hospital length of stay (LOS), discharge status, payer information, charges, and perioperative outcomes and procedure/diagnosis codes (ICD-9; International Classification of Diseases, Ninth Revision¹⁸).

As our Institutional Review Board (IRB) reviewed the database and determined the project was not human subject research, IRB involvement was not required. This study paralleled successful efforts with similar RA and non-RA patients who had shoulder and elbow surgery.^3,19 SA patients were identified by ICD-9 procedure code 81.80, but this code does not specify whether the prosthesis was unconstrained, semiconstrained, or constrained. ICD-9 coding also does not specify whether the TSA was traditional or reverse. Patients with RA were identified by ICD-9 diagnosis codes 714.0, 714.1, and 714.2. Patients without one of these codes were placed in the non-RA cohort. Patients with codes associated with pathologic fractures secondary to metastatic cancer or bone malignant neoplasm as a secondary or primary diagnosis and patients who had revision surgery indicated by code 81.83 were excluded, as they have a disproportionately higher comorbidity burden.

After each cohort was defined, demographic data (age, sex, race, income quartile based on ZIP postal code) were compared, as were data on primary payer, hospital demographics, LOS (≤5 days, defined as perioperative index), discharge type, inflation-adjusted charges in 2014 dollars based on the Consumer Price Indexes (http://www.bls.gov/cpi/), and mortality. Perioperative complications—respiratory, gastrointestinal, genitourinary, accidental puncture/laceration, central nervous system, wound dehiscence, device-related (including embolism, fibrosis, hemorrhage, pain, stenosis, or thrombus caused by any device, implant, or graft), cardiac, hematoma/seroma, acute respiratory distress syndrome, postoperative shock, VTE, postoperative infection complications, and intraoperative transfusions—were considered using ICD-9 codes (996.X-999.X and 99.X, respectively).²⁰ Although commonly used to determine perioperative comorbidity burden using ICD-9 coding, the modified Charlson index was not considered because RA is a component of the index and would therefore bias the variable.^3,21

Statistical analyses, including χ² tests and 2-sample t tests, were performed for categorical and continuous variables, respectively. P < .05 was considered significant. Fisher exact test was used for cohorts with fewer than 5 occurrences. Multivariate logistic regression models were then calculated to determine the effect of RA on different outcomes and complications, with age, race, sex, hospital region, hospital type, number of hospital beds, primary payer, and hospital ownership as covariates. Statistical analyses were performed using the R statistical programming language.22

Results

Of the 34,970 patients who underwent SA between 2006 and 2011, 1674 (4.8%) had a diagnosis of RA and 33,296 (95.2%) did not. On average, patients with RA tended to be younger than patients without RA (66.4 vs 69.1 years; P < .001), and a larger percentage of RA patients were female (75.5% vs 54.4%; P < .001). Compared with non-RA patients, RA patients comprised a different ethnic group and had a different expected primary payer (P < .001). SA patients with and without RA did not differ in income quartile based on ZIP code, total number of hospital beds, hospital region, or hospital teaching status (P = .34, .78, .59, and .82, respectively) (Table 1).

LOS was significantly (P < .001) statistically longer for RA patients (2.196 days) than for non-RA patients (2.085 days). RA patients were significantly less likely to be discharged home (63.0% vs 67.6%; P < .001). (Routine discharge was defined as discharge home, whereas nonroutine discharge was defined as discharge to a short-term hospital, skilled nursing facility, intermediate care, another type of facility, home health care, against medical advice, or death.) In addition, inflation-adjusted charges associated with SA were significantly higher (P = .018) for RA patients ($54,284) than for non-RA patients ($52,663) (Table 1).

Regarding the rates of complications that occurred during the perioperative index, there were no significant differences between RA and non-RA cohorts. These complications included respiratory, gastrointestinal, genitourinary, accidental puncture/laceration, central nervous system, wound dehiscence, device-related, cardiac, hematoma/seroma, acute respiratory distress syndrome, postoperative shock, VTE, and postoperative infection (Table 2). In addition, there was no significant difference in mortality between the groups (P = .48).

In TSA, blood transfusions were more likely (P < .001) to be given to RA patients (9.00%) than to non-RA patients (6.16%). Multivariate regression analyses were performed with age, race, sex, hospital region, hospital type, number of hospital beds, primary payer, and hospital ownership as covariates. These analyses revealed that transfusion (P < .001), discharge type (P = .002), total inflation-adjusted charges (P < .001), and LOS (P = .047) remained significant (Table 3).

Discussion

Large national databases like NIS allow study of uncommon medical occurrences and help delineate risks and trends that otherwise might be indeterminable. Although it has been suggested that patients with RA may have poorer long-term outcomes after SA, the perioperative risk profile indicates that TSA is well tolerated in RA patients during the operative index.^3,23-25

The data on this study’s 34,970 patients, drawn from the period 2006–2011, demonstrated no significant differences in safety profile with respect to the 14 perioperative complications and outcomes examined, except blood transfusion rate. Rates of postoperative infection (RA, 0.24%; non-RA, 0.14%; P = .303), VTE (RA, 0.30%; non-RA, 0.25%; P = .905), and transfusion (RA, 9.00%; non-RA, 6.16%; P < .001) are of particular interest because of the severity of these situations.

Postoperative infection is a potentially serious complication and often occurs secondary to diabetes, RA, lupus erythematosus, prior surgery, or a nosocomial or remote source.¹ The often costly treatment options include antibiotic suppression, irrigation and debridement with implant retention, 1-stage exchange with antibiotic-impregnated cement fixation, staged reimplantation, resection arthroplasty, arthrodesis, and amputation.¹ The overall 0.14% infection rate determined in this study is lower than the 0.7% reported for SA patients in the literature.¹ Given the nature of the NIS database, this rate underestimates the true postoperative infection rate, as any infection that occurred after the perioperative period is not captured.²⁶ The present study’s perioperative infection rates (RA, 0.24%; non-RA, 0.14%) for the period 2006–2011 are comparable to the rates (RA, 0.17%; non-RA, 0.24%) reported by Hambright and colleagues3 for the same patient population over the preceding, 18-year period (1988–2005) and similarly do not significantly differ between groups. Although infection is uncommon in the immediate perioperative period, the ICD-9 codes used refer specifically to infection resulting from surgery and do not represent concomitant infection.

VTEs, which include PEs and DVTs, are rare but potentially life-threatening surgical complications.^27,28 Mechanical prophylaxis and chemical prophylaxis have been recommended for major orthopedic surgery, particularly lower extremity surgery, such as total hip arthroplasty (THA) and total knee arthroplasty (TKA).^28,29 In the present study, VTE rates were low, 0.30% (RA) and 0.25% (non-RA), and not significantly different in bivariate or multivariate analyses. These rates are comparable to those found in other national-database SA studies.²⁸ VTEs that occur outside the index hospital admission are not captured in this database. Therefore, the rates in the present study may be lower than the true incidence after SA. Mortality secondary to VTE usually occurs within 24 hours but may occur up to 90 days after surgery. DVT rates, on the other hand, are difficult to evaluate because of differences in screening practices.^27,28,30,31

That RA patients were more likely than non-RA patients to receive perioperative blood transfusions supports prior findings that SA patients with RA were more likely than SA patients with osteoarthritis (OA) to receive perioperative blood transfusions.⁸ RA patients have been shown to have high rates of anemia of chronic disease, ranging from 22% to 77%.³² During joint replacement, these patients often require transfusions.^32,33 However, these findings differ from prior findings of no differences between RA and non-RA patients in the same patient population during the period 1988–2005.³ This difference may be a product of the constantly changing transfusion guidelines and increased use; transfusion rates increased 140% between 1997 and 2007, making transfusions the fastest growing common procedure in the United States during that time.³⁴ There was no difference between RA and non-RA patients in household income (as determined by ZIP code analysis), number of hospital beds, hospital region, or hospital teaching status. Compared with non-RA patients, RA patients were more likely to be younger, female, and of a difference race and to have a different expected primary payer (P < .001).These findings are consistent with previous findings in the literature.³ In the present SA study, however, RA patients were more likely than non-RA patients to have longer LOS, higher inflation-adjusted hospital charges, and nonroutine discharge. These findings deviate from those of the study covering the preceding 18 years (1988–2005).³ Despite the findings of a changing environment of care for RA patients, by Hambright and colleagues³ and Weiss and colleagues,³⁵ the trend appears to have shifted. Both groups had shorter average LOS than either group from the preceding 18 years.³ Although statistically significant in bivariate analysis, the difference in LOS between the 2 groups differed by an average of 0.11 day (2 hours 24 minutes) and was not clinically relevant.

In addition, the higher charges for patients with RA represent a deviation from the preceding 18 years.³ Other studies have also shown that RA is associated with increased cost in TSA.³⁶ Patients with RA often have rotator cuff pathology, indicating reverse SA may be used more frequently.^37,38 The increased implant cost associated with reverse SA may account for the increased costs in RA patients.³⁹ As mentioned, TSA type is not captured in the NIS database. In addition, that RA patients were less likely than non-RA patients to have routine discharge may indicate RA cases are more complex because of their complications.^1,5,14,40 A recent study of complications in RA patients (1163 who underwent THA, 2692 who underwent TKA) found that THA patients with RA were significantly more likely than THA patients with OA to dislocate, and TKA patients with RA were significantly more likely than TKA patients with OA to develop an infection after surgery.⁴¹ Postoperative dislocation has been shown to increase hospital costs in other orthopedic procedures.⁴² Also, during TSA, patients with RA are more likely than patients with OA to receive intraoperative blood transfusions.⁸ These complications—combined with the fact that RA is a chronic, progressive, systemic inflammatory disease that can affect soft tissue and blood vessel wall healing and is associated with medications having potential side effects—could contribute to the apparent increased hospital charges and LOS.^3,12,13,43 Factors that include surgeon preference, impact of primary payer, and hospital practice may also affect final charges. Total charges in the NIS database include administrative fees, hospital costs, device-related costs, operating room costs, and ancillary staff costs. Total charges do not include professional fees and differ from the total cost that represents the amount reimbursed by the payer. Charges tend to correlate with but overestimate the total costs.⁴⁴

This study had several important limitations. As mentioned, only events that occur during the operative admission are captured in the NIS database, and thus postoperative complications or serious adverse events that lead to readmission cannot be identified. In addition, outpatient TSAs are not captured in the NIS database, and thus inclusion of only inpatient procedures yields higher average LOS and total charges.⁴⁵ Given the limited granularity of ICD-9 coding, this study could not determine RA severity, estimated blood loss, length of surgery, complication severity, type of TSA procedure/prosthesis, or cause of death. Although commonly used to determine comorbidity burden, the modified Charlson index could not be used, and therefore could not be entered as a covariate in multivariate analysis. Furthermore, the NIS database does not include imaging or patient-reported outcomes information, such as improvements in pain or function, which are of crucial importance in considering surgery.

Conclusion

Our findings corroborated findings that the demographics and the perioperative safety profile for TSA were similar for patients with and without RA. The risk for complications or death in the perioperative period was low. Compared with non-RA patients, RA patients had significantly higher charges and longer LOS and were less likely to be discharged home after surgery. The 0.11-day difference in LOS, though statistically significant, was not clinically relevant. These findings differ from those for the preceding, 18-year period (1988–2005). Future research should focus on the causes of these changes.

Shoulder arthroplasty (SA), including total SA (TSA) and reverse TSA, is an effective surgical treatment for fracture and primary or secondary degenerative disease of the shoulder.¹ Over the past few decades, use of SA has increased dramatically, from about 5000 cases in 1990 to 7000 in 2000 and more than 26,000 in 2008.^1,2

Complications associated with SA generally are classified as perioperative (occurring during the operative index) or long-term (postdischarge).³ Long-term complications include implant loosening, instability, revision, infection, rotator cuff tear, neural injury, and deltoid detachment.^1,4,5 Perioperative complications, which are less commonly reported, include intraoperative fracture, infection, neural injury, venous thromboembolic events (VTEs, including pulmonary embolism [PE] and deep vein thrombosis [DVT]), transfusion, and death.^3,6-10

SA is an attractive treatment option for patients with rheumatoid arthritis (RA), as the effects of pain on these patients are greater in the shoulder joint than in any other joint.¹¹ Patients with RA pose unique orthopedic surgical challenges, including any combination of decreased bone mineralization, poor capsular tissue integrity, and osteonecrosis.^3,12 In addition, RA patients may be taking immunosuppressive medications that have severe side effects, and they may require multiple surgeries.^12,13 These factors predispose patients with RA to complications that include infection and wound dehiscence.^3,5,12-14

The complex nature of RA has prompted investigators to examine outcome measures in this patient group. Hambright and colleagues³ used the Nationwide Inpatient Sample (NIS) to examine perioperative outcomes in RA patients who underwent TSA between 1988 and 2005.³ They found that TSA patients with RA had shorter and less costly hospital stays and were more likely to have a routine discharge.³ Using the same patient population drawn from the period 2006–2011, we conducted a study to determine if this unexpected trend persists as the number of TSAs and quality of postoperative care continue to increase. Given the potential for anemia of chronic disease and the systemic inflammatory nature of RA, we hypothesized that the perioperative complication profile of RA patients would be worse than that of non-RA patients.

Materials and Methods

NIS data were acquired for the period 2006–2011. The NIS is the largest publicly available all-payer inpatient database, with a random 20% sample of about 1000 US hospitals accounting for 7 to 8 million inpatient stays. The database supplies weights used to estimate national totals, at about 35 million inpatient visits per year. NIS inpatient data are limited to the operative index. Postdischarge information is not available. The NIS is managed by the Healthcare Cost and Utilization Project, which is sponsored by the Agency for Healthcare Research and Quality. The quality of NIS data is assessed and validated by an independent contractor. NIS data have been widely used to examine perioperative outcomes.^15-17

NIS data cover patient and hospital demographics, hospital length of stay (LOS), discharge status, payer information, charges, and perioperative outcomes and procedure/diagnosis codes (ICD-9; International Classification of Diseases, Ninth Revision¹⁸).

As our Institutional Review Board (IRB) reviewed the database and determined the project was not human subject research, IRB involvement was not required. This study paralleled successful efforts with similar RA and non-RA patients who had shoulder and elbow surgery.^3,19 SA patients were identified by ICD-9 procedure code 81.80, but this code does not specify whether the prosthesis was unconstrained, semiconstrained, or constrained. ICD-9 coding also does not specify whether the TSA was traditional or reverse. Patients with RA were identified by ICD-9 diagnosis codes 714.0, 714.1, and 714.2. Patients without one of these codes were placed in the non-RA cohort. Patients with codes associated with pathologic fractures secondary to metastatic cancer or bone malignant neoplasm as a secondary or primary diagnosis and patients who had revision surgery indicated by code 81.83 were excluded, as they have a disproportionately higher comorbidity burden.

After each cohort was defined, demographic data (age, sex, race, income quartile based on ZIP postal code) were compared, as were data on primary payer, hospital demographics, LOS (≤5 days, defined as perioperative index), discharge type, inflation-adjusted charges in 2014 dollars based on the Consumer Price Indexes (http://www.bls.gov/cpi/), and mortality. Perioperative complications—respiratory, gastrointestinal, genitourinary, accidental puncture/laceration, central nervous system, wound dehiscence, device-related (including embolism, fibrosis, hemorrhage, pain, stenosis, or thrombus caused by any device, implant, or graft), cardiac, hematoma/seroma, acute respiratory distress syndrome, postoperative shock, VTE, postoperative infection complications, and intraoperative transfusions—were considered using ICD-9 codes (996.X-999.X and 99.X, respectively).²⁰ Although commonly used to determine perioperative comorbidity burden using ICD-9 coding, the modified Charlson index was not considered because RA is a component of the index and would therefore bias the variable.^3,21

Statistical analyses, including χ² tests and 2-sample t tests, were performed for categorical and continuous variables, respectively. P < .05 was considered significant. Fisher exact test was used for cohorts with fewer than 5 occurrences. Multivariate logistic regression models were then calculated to determine the effect of RA on different outcomes and complications, with age, race, sex, hospital region, hospital type, number of hospital beds, primary payer, and hospital ownership as covariates. Statistical analyses were performed using the R statistical programming language.22

Results

Of the 34,970 patients who underwent SA between 2006 and 2011, 1674 (4.8%) had a diagnosis of RA and 33,296 (95.2%) did not. On average, patients with RA tended to be younger than patients without RA (66.4 vs 69.1 years; P < .001), and a larger percentage of RA patients were female (75.5% vs 54.4%; P < .001). Compared with non-RA patients, RA patients comprised a different ethnic group and had a different expected primary payer (P < .001). SA patients with and without RA did not differ in income quartile based on ZIP code, total number of hospital beds, hospital region, or hospital teaching status (P = .34, .78, .59, and .82, respectively) (Table 1).

LOS was significantly (P < .001) statistically longer for RA patients (2.196 days) than for non-RA patients (2.085 days). RA patients were significantly less likely to be discharged home (63.0% vs 67.6%; P < .001). (Routine discharge was defined as discharge home, whereas nonroutine discharge was defined as discharge to a short-term hospital, skilled nursing facility, intermediate care, another type of facility, home health care, against medical advice, or death.) In addition, inflation-adjusted charges associated with SA were significantly higher (P = .018) for RA patients ($54,284) than for non-RA patients ($52,663) (Table 1).

Regarding the rates of complications that occurred during the perioperative index, there were no significant differences between RA and non-RA cohorts. These complications included respiratory, gastrointestinal, genitourinary, accidental puncture/laceration, central nervous system, wound dehiscence, device-related, cardiac, hematoma/seroma, acute respiratory distress syndrome, postoperative shock, VTE, and postoperative infection (Table 2). In addition, there was no significant difference in mortality between the groups (P = .48).

In TSA, blood transfusions were more likely (P < .001) to be given to RA patients (9.00%) than to non-RA patients (6.16%). Multivariate regression analyses were performed with age, race, sex, hospital region, hospital type, number of hospital beds, primary payer, and hospital ownership as covariates. These analyses revealed that transfusion (P < .001), discharge type (P = .002), total inflation-adjusted charges (P < .001), and LOS (P = .047) remained significant (Table 3).

Discussion

Large national databases like NIS allow study of uncommon medical occurrences and help delineate risks and trends that otherwise might be indeterminable. Although it has been suggested that patients with RA may have poorer long-term outcomes after SA, the perioperative risk profile indicates that TSA is well tolerated in RA patients during the operative index.^3,23-25

The data on this study’s 34,970 patients, drawn from the period 2006–2011, demonstrated no significant differences in safety profile with respect to the 14 perioperative complications and outcomes examined, except blood transfusion rate. Rates of postoperative infection (RA, 0.24%; non-RA, 0.14%; P = .303), VTE (RA, 0.30%; non-RA, 0.25%; P = .905), and transfusion (RA, 9.00%; non-RA, 6.16%; P < .001) are of particular interest because of the severity of these situations.

Postoperative infection is a potentially serious complication and often occurs secondary to diabetes, RA, lupus erythematosus, prior surgery, or a nosocomial or remote source.¹ The often costly treatment options include antibiotic suppression, irrigation and debridement with implant retention, 1-stage exchange with antibiotic-impregnated cement fixation, staged reimplantation, resection arthroplasty, arthrodesis, and amputation.¹ The overall 0.14% infection rate determined in this study is lower than the 0.7% reported for SA patients in the literature.¹ Given the nature of the NIS database, this rate underestimates the true postoperative infection rate, as any infection that occurred after the perioperative period is not captured.²⁶ The present study’s perioperative infection rates (RA, 0.24%; non-RA, 0.14%) for the period 2006–2011 are comparable to the rates (RA, 0.17%; non-RA, 0.24%) reported by Hambright and colleagues3 for the same patient population over the preceding, 18-year period (1988–2005) and similarly do not significantly differ between groups. Although infection is uncommon in the immediate perioperative period, the ICD-9 codes used refer specifically to infection resulting from surgery and do not represent concomitant infection.

VTEs, which include PEs and DVTs, are rare but potentially life-threatening surgical complications.^27,28 Mechanical prophylaxis and chemical prophylaxis have been recommended for major orthopedic surgery, particularly lower extremity surgery, such as total hip arthroplasty (THA) and total knee arthroplasty (TKA).^28,29 In the present study, VTE rates were low, 0.30% (RA) and 0.25% (non-RA), and not significantly different in bivariate or multivariate analyses. These rates are comparable to those found in other national-database SA studies.²⁸ VTEs that occur outside the index hospital admission are not captured in this database. Therefore, the rates in the present study may be lower than the true incidence after SA. Mortality secondary to VTE usually occurs within 24 hours but may occur up to 90 days after surgery. DVT rates, on the other hand, are difficult to evaluate because of differences in screening practices.^27,28,30,31

That RA patients were more likely than non-RA patients to receive perioperative blood transfusions supports prior findings that SA patients with RA were more likely than SA patients with osteoarthritis (OA) to receive perioperative blood transfusions.⁸ RA patients have been shown to have high rates of anemia of chronic disease, ranging from 22% to 77%.³² During joint replacement, these patients often require transfusions.^32,33 However, these findings differ from prior findings of no differences between RA and non-RA patients in the same patient population during the period 1988–2005.³ This difference may be a product of the constantly changing transfusion guidelines and increased use; transfusion rates increased 140% between 1997 and 2007, making transfusions the fastest growing common procedure in the United States during that time.³⁴ There was no difference between RA and non-RA patients in household income (as determined by ZIP code analysis), number of hospital beds, hospital region, or hospital teaching status. Compared with non-RA patients, RA patients were more likely to be younger, female, and of a difference race and to have a different expected primary payer (P < .001).These findings are consistent with previous findings in the literature.³ In the present SA study, however, RA patients were more likely than non-RA patients to have longer LOS, higher inflation-adjusted hospital charges, and nonroutine discharge. These findings deviate from those of the study covering the preceding 18 years (1988–2005).³ Despite the findings of a changing environment of care for RA patients, by Hambright and colleagues³ and Weiss and colleagues,³⁵ the trend appears to have shifted. Both groups had shorter average LOS than either group from the preceding 18 years.³ Although statistically significant in bivariate analysis, the difference in LOS between the 2 groups differed by an average of 0.11 day (2 hours 24 minutes) and was not clinically relevant.

In addition, the higher charges for patients with RA represent a deviation from the preceding 18 years.³ Other studies have also shown that RA is associated with increased cost in TSA.³⁶ Patients with RA often have rotator cuff pathology, indicating reverse SA may be used more frequently.^37,38 The increased implant cost associated with reverse SA may account for the increased costs in RA patients.³⁹ As mentioned, TSA type is not captured in the NIS database. In addition, that RA patients were less likely than non-RA patients to have routine discharge may indicate RA cases are more complex because of their complications.^1,5,14,40 A recent study of complications in RA patients (1163 who underwent THA, 2692 who underwent TKA) found that THA patients with RA were significantly more likely than THA patients with OA to dislocate, and TKA patients with RA were significantly more likely than TKA patients with OA to develop an infection after surgery.⁴¹ Postoperative dislocation has been shown to increase hospital costs in other orthopedic procedures.⁴² Also, during TSA, patients with RA are more likely than patients with OA to receive intraoperative blood transfusions.⁸ These complications—combined with the fact that RA is a chronic, progressive, systemic inflammatory disease that can affect soft tissue and blood vessel wall healing and is associated with medications having potential side effects—could contribute to the apparent increased hospital charges and LOS.^3,12,13,43 Factors that include surgeon preference, impact of primary payer, and hospital practice may also affect final charges. Total charges in the NIS database include administrative fees, hospital costs, device-related costs, operating room costs, and ancillary staff costs. Total charges do not include professional fees and differ from the total cost that represents the amount reimbursed by the payer. Charges tend to correlate with but overestimate the total costs.⁴⁴

This study had several important limitations. As mentioned, only events that occur during the operative admission are captured in the NIS database, and thus postoperative complications or serious adverse events that lead to readmission cannot be identified. In addition, outpatient TSAs are not captured in the NIS database, and thus inclusion of only inpatient procedures yields higher average LOS and total charges.⁴⁵ Given the limited granularity of ICD-9 coding, this study could not determine RA severity, estimated blood loss, length of surgery, complication severity, type of TSA procedure/prosthesis, or cause of death. Although commonly used to determine comorbidity burden, the modified Charlson index could not be used, and therefore could not be entered as a covariate in multivariate analysis. Furthermore, the NIS database does not include imaging or patient-reported outcomes information, such as improvements in pain or function, which are of crucial importance in considering surgery.

Conclusion

Our findings corroborated findings that the demographics and the perioperative safety profile for TSA were similar for patients with and without RA. The risk for complications or death in the perioperative period was low. Compared with non-RA patients, RA patients had significantly higher charges and longer LOS and were less likely to be discharged home after surgery. The 0.11-day difference in LOS, though statistically significant, was not clinically relevant. These findings differ from those for the preceding, 18-year period (1988–2005). Future research should focus on the causes of these changes.

Shoulder arthroplasty (SA), including total SA (TSA) and reverse TSA, is an effective surgical treatment for fracture and primary or secondary degenerative disease of the shoulder.¹ Over the past few decades, use of SA has increased dramatically, from about 5000 cases in 1990 to 7000 in 2000 and more than 26,000 in 2008.^1,2

Complications associated with SA generally are classified as perioperative (occurring during the operative index) or long-term (postdischarge).³ Long-term complications include implant loosening, instability, revision, infection, rotator cuff tear, neural injury, and deltoid detachment.^1,4,5 Perioperative complications, which are less commonly reported, include intraoperative fracture, infection, neural injury, venous thromboembolic events (VTEs, including pulmonary embolism [PE] and deep vein thrombosis [DVT]), transfusion, and death.^3,6-10

SA is an attractive treatment option for patients with rheumatoid arthritis (RA), as the effects of pain on these patients are greater in the shoulder joint than in any other joint.¹¹ Patients with RA pose unique orthopedic surgical challenges, including any combination of decreased bone mineralization, poor capsular tissue integrity, and osteonecrosis.^3,12 In addition, RA patients may be taking immunosuppressive medications that have severe side effects, and they may require multiple surgeries.^12,13 These factors predispose patients with RA to complications that include infection and wound dehiscence.^3,5,12-14

The complex nature of RA has prompted investigators to examine outcome measures in this patient group. Hambright and colleagues³ used the Nationwide Inpatient Sample (NIS) to examine perioperative outcomes in RA patients who underwent TSA between 1988 and 2005.³ They found that TSA patients with RA had shorter and less costly hospital stays and were more likely to have a routine discharge.³ Using the same patient population drawn from the period 2006–2011, we conducted a study to determine if this unexpected trend persists as the number of TSAs and quality of postoperative care continue to increase. Given the potential for anemia of chronic disease and the systemic inflammatory nature of RA, we hypothesized that the perioperative complication profile of RA patients would be worse than that of non-RA patients.

Materials and Methods

NIS data were acquired for the period 2006–2011. The NIS is the largest publicly available all-payer inpatient database, with a random 20% sample of about 1000 US hospitals accounting for 7 to 8 million inpatient stays. The database supplies weights used to estimate national totals, at about 35 million inpatient visits per year. NIS inpatient data are limited to the operative index. Postdischarge information is not available. The NIS is managed by the Healthcare Cost and Utilization Project, which is sponsored by the Agency for Healthcare Research and Quality. The quality of NIS data is assessed and validated by an independent contractor. NIS data have been widely used to examine perioperative outcomes.^15-17

NIS data cover patient and hospital demographics, hospital length of stay (LOS), discharge status, payer information, charges, and perioperative outcomes and procedure/diagnosis codes (ICD-9; International Classification of Diseases, Ninth Revision¹⁸).

As our Institutional Review Board (IRB) reviewed the database and determined the project was not human subject research, IRB involvement was not required. This study paralleled successful efforts with similar RA and non-RA patients who had shoulder and elbow surgery.^3,19 SA patients were identified by ICD-9 procedure code 81.80, but this code does not specify whether the prosthesis was unconstrained, semiconstrained, or constrained. ICD-9 coding also does not specify whether the TSA was traditional or reverse. Patients with RA were identified by ICD-9 diagnosis codes 714.0, 714.1, and 714.2. Patients without one of these codes were placed in the non-RA cohort. Patients with codes associated with pathologic fractures secondary to metastatic cancer or bone malignant neoplasm as a secondary or primary diagnosis and patients who had revision surgery indicated by code 81.83 were excluded, as they have a disproportionately higher comorbidity burden.

After each cohort was defined, demographic data (age, sex, race, income quartile based on ZIP postal code) were compared, as were data on primary payer, hospital demographics, LOS (≤5 days, defined as perioperative index), discharge type, inflation-adjusted charges in 2014 dollars based on the Consumer Price Indexes (http://www.bls.gov/cpi/), and mortality. Perioperative complications—respiratory, gastrointestinal, genitourinary, accidental puncture/laceration, central nervous system, wound dehiscence, device-related (including embolism, fibrosis, hemorrhage, pain, stenosis, or thrombus caused by any device, implant, or graft), cardiac, hematoma/seroma, acute respiratory distress syndrome, postoperative shock, VTE, postoperative infection complications, and intraoperative transfusions—were considered using ICD-9 codes (996.X-999.X and 99.X, respectively).²⁰ Although commonly used to determine perioperative comorbidity burden using ICD-9 coding, the modified Charlson index was not considered because RA is a component of the index and would therefore bias the variable.^3,21

Statistical analyses, including χ² tests and 2-sample t tests, were performed for categorical and continuous variables, respectively. P < .05 was considered significant. Fisher exact test was used for cohorts with fewer than 5 occurrences. Multivariate logistic regression models were then calculated to determine the effect of RA on different outcomes and complications, with age, race, sex, hospital region, hospital type, number of hospital beds, primary payer, and hospital ownership as covariates. Statistical analyses were performed using the R statistical programming language.22

Results

Of the 34,970 patients who underwent SA between 2006 and 2011, 1674 (4.8%) had a diagnosis of RA and 33,296 (95.2%) did not. On average, patients with RA tended to be younger than patients without RA (66.4 vs 69.1 years; P < .001), and a larger percentage of RA patients were female (75.5% vs 54.4%; P < .001). Compared with non-RA patients, RA patients comprised a different ethnic group and had a different expected primary payer (P < .001). SA patients with and without RA did not differ in income quartile based on ZIP code, total number of hospital beds, hospital region, or hospital teaching status (P = .34, .78, .59, and .82, respectively) (Table 1).

LOS was significantly (P < .001) statistically longer for RA patients (2.196 days) than for non-RA patients (2.085 days). RA patients were significantly less likely to be discharged home (63.0% vs 67.6%; P < .001). (Routine discharge was defined as discharge home, whereas nonroutine discharge was defined as discharge to a short-term hospital, skilled nursing facility, intermediate care, another type of facility, home health care, against medical advice, or death.) In addition, inflation-adjusted charges associated with SA were significantly higher (P = .018) for RA patients ($54,284) than for non-RA patients ($52,663) (Table 1).

Regarding the rates of complications that occurred during the perioperative index, there were no significant differences between RA and non-RA cohorts. These complications included respiratory, gastrointestinal, genitourinary, accidental puncture/laceration, central nervous system, wound dehiscence, device-related, cardiac, hematoma/seroma, acute respiratory distress syndrome, postoperative shock, VTE, and postoperative infection (Table 2). In addition, there was no significant difference in mortality between the groups (P = .48).

In TSA, blood transfusions were more likely (P < .001) to be given to RA patients (9.00%) than to non-RA patients (6.16%). Multivariate regression analyses were performed with age, race, sex, hospital region, hospital type, number of hospital beds, primary payer, and hospital ownership as covariates. These analyses revealed that transfusion (P < .001), discharge type (P = .002), total inflation-adjusted charges (P < .001), and LOS (P = .047) remained significant (Table 3).

Discussion

Large national databases like NIS allow study of uncommon medical occurrences and help delineate risks and trends that otherwise might be indeterminable. Although it has been suggested that patients with RA may have poorer long-term outcomes after SA, the perioperative risk profile indicates that TSA is well tolerated in RA patients during the operative index.^3,23-25

The data on this study’s 34,970 patients, drawn from the period 2006–2011, demonstrated no significant differences in safety profile with respect to the 14 perioperative complications and outcomes examined, except blood transfusion rate. Rates of postoperative infection (RA, 0.24%; non-RA, 0.14%; P = .303), VTE (RA, 0.30%; non-RA, 0.25%; P = .905), and transfusion (RA, 9.00%; non-RA, 6.16%; P < .001) are of particular interest because of the severity of these situations.

Postoperative infection is a potentially serious complication and often occurs secondary to diabetes, RA, lupus erythematosus, prior surgery, or a nosocomial or remote source.¹ The often costly treatment options include antibiotic suppression, irrigation and debridement with implant retention, 1-stage exchange with antibiotic-impregnated cement fixation, staged reimplantation, resection arthroplasty, arthrodesis, and amputation.¹ The overall 0.14% infection rate determined in this study is lower than the 0.7% reported for SA patients in the literature.¹ Given the nature of the NIS database, this rate underestimates the true postoperative infection rate, as any infection that occurred after the perioperative period is not captured.²⁶ The present study’s perioperative infection rates (RA, 0.24%; non-RA, 0.14%) for the period 2006–2011 are comparable to the rates (RA, 0.17%; non-RA, 0.24%) reported by Hambright and colleagues3 for the same patient population over the preceding, 18-year period (1988–2005) and similarly do not significantly differ between groups. Although infection is uncommon in the immediate perioperative period, the ICD-9 codes used refer specifically to infection resulting from surgery and do not represent concomitant infection.

VTEs, which include PEs and DVTs, are rare but potentially life-threatening surgical complications.^27,28 Mechanical prophylaxis and chemical prophylaxis have been recommended for major orthopedic surgery, particularly lower extremity surgery, such as total hip arthroplasty (THA) and total knee arthroplasty (TKA).^28,29 In the present study, VTE rates were low, 0.30% (RA) and 0.25% (non-RA), and not significantly different in bivariate or multivariate analyses. These rates are comparable to those found in other national-database SA studies.²⁸ VTEs that occur outside the index hospital admission are not captured in this database. Therefore, the rates in the present study may be lower than the true incidence after SA. Mortality secondary to VTE usually occurs within 24 hours but may occur up to 90 days after surgery. DVT rates, on the other hand, are difficult to evaluate because of differences in screening practices.^27,28,30,31

That RA patients were more likely than non-RA patients to receive perioperative blood transfusions supports prior findings that SA patients with RA were more likely than SA patients with osteoarthritis (OA) to receive perioperative blood transfusions.⁸ RA patients have been shown to have high rates of anemia of chronic disease, ranging from 22% to 77%.³² During joint replacement, these patients often require transfusions.^32,33 However, these findings differ from prior findings of no differences between RA and non-RA patients in the same patient population during the period 1988–2005.³ This difference may be a product of the constantly changing transfusion guidelines and increased use; transfusion rates increased 140% between 1997 and 2007, making transfusions the fastest growing common procedure in the United States during that time.³⁴ There was no difference between RA and non-RA patients in household income (as determined by ZIP code analysis), number of hospital beds, hospital region, or hospital teaching status. Compared with non-RA patients, RA patients were more likely to be younger, female, and of a difference race and to have a different expected primary payer (P < .001).These findings are consistent with previous findings in the literature.³ In the present SA study, however, RA patients were more likely than non-RA patients to have longer LOS, higher inflation-adjusted hospital charges, and nonroutine discharge. These findings deviate from those of the study covering the preceding 18 years (1988–2005).³ Despite the findings of a changing environment of care for RA patients, by Hambright and colleagues³ and Weiss and colleagues,³⁵ the trend appears to have shifted. Both groups had shorter average LOS than either group from the preceding 18 years.³ Although statistically significant in bivariate analysis, the difference in LOS between the 2 groups differed by an average of 0.11 day (2 hours 24 minutes) and was not clinically relevant.

In addition, the higher charges for patients with RA represent a deviation from the preceding 18 years.³ Other studies have also shown that RA is associated with increased cost in TSA.³⁶ Patients with RA often have rotator cuff pathology, indicating reverse SA may be used more frequently.^37,38 The increased implant cost associated with reverse SA may account for the increased costs in RA patients.³⁹ As mentioned, TSA type is not captured in the NIS database. In addition, that RA patients were less likely than non-RA patients to have routine discharge may indicate RA cases are more complex because of their complications.^1,5,14,40 A recent study of complications in RA patients (1163 who underwent THA, 2692 who underwent TKA) found that THA patients with RA were significantly more likely than THA patients with OA to dislocate, and TKA patients with RA were significantly more likely than TKA patients with OA to develop an infection after surgery.⁴¹ Postoperative dislocation has been shown to increase hospital costs in other orthopedic procedures.⁴² Also, during TSA, patients with RA are more likely than patients with OA to receive intraoperative blood transfusions.⁸ These complications—combined with the fact that RA is a chronic, progressive, systemic inflammatory disease that can affect soft tissue and blood vessel wall healing and is associated with medications having potential side effects—could contribute to the apparent increased hospital charges and LOS.^3,12,13,43 Factors that include surgeon preference, impact of primary payer, and hospital practice may also affect final charges. Total charges in the NIS database include administrative fees, hospital costs, device-related costs, operating room costs, and ancillary staff costs. Total charges do not include professional fees and differ from the total cost that represents the amount reimbursed by the payer. Charges tend to correlate with but overestimate the total costs.⁴⁴

This study had several important limitations. As mentioned, only events that occur during the operative admission are captured in the NIS database, and thus postoperative complications or serious adverse events that lead to readmission cannot be identified. In addition, outpatient TSAs are not captured in the NIS database, and thus inclusion of only inpatient procedures yields higher average LOS and total charges.⁴⁵ Given the limited granularity of ICD-9 coding, this study could not determine RA severity, estimated blood loss, length of surgery, complication severity, type of TSA procedure/prosthesis, or cause of death. Although commonly used to determine comorbidity burden, the modified Charlson index could not be used, and therefore could not be entered as a covariate in multivariate analysis. Furthermore, the NIS database does not include imaging or patient-reported outcomes information, such as improvements in pain or function, which are of crucial importance in considering surgery.

Conclusion

Our findings corroborated findings that the demographics and the perioperative safety profile for TSA were similar for patients with and without RA. The risk for complications or death in the perioperative period was low. Compared with non-RA patients, RA patients had significantly higher charges and longer LOS and were less likely to be discharged home after surgery. The 0.11-day difference in LOS, though statistically significant, was not clinically relevant. These findings differ from those for the preceding, 18-year period (1988–2005). Future research should focus on the causes of these changes.

A radial nerve injury in association with a humeral shaft fracture is not an infrequent occurrence.^1,2 The nerve injury typically is thought to be a neurapraxia caused by a contusion, as spontaneous recovery rates range from 70% to 90%.^2-4 In cases in which acute nerve exploration and open reduction and internal fixation (ORIF) are not indicated, patient and clinician wait months for the nerve to recover. In some conservatively treated cases, the nerve is lacerated or entrapped. Patients with a lacerated or entrapped nerve may have better outcomes with early operative management.

We report on a rare case of the radial nerve entrapped within a nondisplaced segment of a closed humeral shaft fracture and describe the clinical outcome of early operative management. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An intoxicated, restrained 18-year-old driver in a motor vehicle collision sustained multiple injuries, including rib fracture, apical pneumothorax with pulmonary contusion, and corneal abrasion. Orthopedic injuries included right subtrochanteric femur fracture and midshaft right humeral shaft fracture (Figure 1).

Initial orthopedic evaluation of the right arm revealed decreased sensation in the radial nerve distribution. Motor function in the radial nerve was absent; the patient was incapable of active wrist extension or finger extension. Median and ulnar nerves were motor- and sensory-intact. Radiographs showed a displaced transverse midshaft humeral shaft fracture with a minimally displaced vertical fracture line extending from the fracture site about 3 cm into the proximal segment. The patient was placed in a coaptation splint. The femur fracture was treated with an antegrade piriformis entry intramedullary nail.

ORIF of the humerus was performed to facilitate mobilization of this polytrauma patient. He was positioned prone on a flat-top table with his right arm over a radiolucent extension. The arm was abducted at the shoulder and the elbow flexed. A posterior midline skin incision was made to reflect the triceps in a lateral-to-medial direction, facilitating dissection of the lateral brachial cutaneous nerve on the lateral aspect of the triceps, with resultant localization of the radial nerve. At that time, the radial nerve was noted to be entrapped in the fracture site (Figure 2). In the proximal segment was a sagittal split, displaced about 1 mm, and it was in this interval the nerve was held. This sagittal fracture appeared incomplete as it was followed more proximally. A unicortical Kirschner wire was placed in a posterior-to-anterior direction in each fragment alongside the nerve. A lamina spreader engaged the wires and distracted the fracture site as the tines were spread apart, releasing the nerve (Figure 3). The nerve was in continuity but was severely contused at that location. After the sagittal split was reduced, two 2.7-mm lag screws were used in lag fashion, and the transverse midshaft component was fixed with a 10-hole, 4.5-mm narrow locking compression plate. The radial nerve lay on the posterior aspect of the plate, between holes 4 and 5 (Figures 4, 5). The wound was closed, and the patient was made weight-bearing as tolerated in the right upper extremity. He was sent to occupational therapy, and static and dynamic splints were made for his wrist and hand.

Two months after injury, radial nerve examination findings were unchanged: decreased sensation on dorsum of hand and no motor function. At 3 months, electrodiagnostic testing showed neurophysiologic evidence of severe right radial neuropathy proximal to the innervation of the right brachioradialis. There were electrodiagnostic signs of ongoing axonal loss and no signs of ongoing reinnervation. At 4 months, only motor strength in wrist extension was improved (2/5). At 5 months, the patient had 4–/5 wrist extension, 3/5 metacarpophalangeal (MCP) extension of fingers, and 0/5 MCP/interphalangeal extension of thumb. Sensation in the radial nerve distribution was still decreased. At 7 months, strength in wrist extension and finger MCP extension was 4+/5. The fracture was now well healed, with maintained alignment and no changes in hardware appearance.

Discussion

In most cases, closed treatment of a humeral shaft fracture with an associated radial nerve injury has a successful outcome.⁵ The etiology of the neurapraxia likely is nerve contusion after the fracture. A neurapraxia is by definition a temporary injury to the myelin sheath with an intact nerve; the nerve function recovers rapidly.

Some humeral shaft fractures, however, have been associated with radial nerve injuries more severe than contusions, resulting in axonotmesis or neurotmesis. These more severe injuries make up 10% to 30% of humeral shaft fractures, including those with a frank laceration of the nerve and those with an entrapped nerve.^2,3 Shao and colleagues² reported a 90% recovery rate for patients who delayed extrication of the entrapped radial nerve. Although there is no consensus on timing of surgical exploration, motor and sensory function of the nerve is temporally related, which may indicate that earlier diagnosis and treatment lead to improved outcome.^6,7 Loss of radial nerve function can have devastating effects on upper extremity function. Often, patients lose all or some extension of the wrist and fingers and abduction and extension of the thumb.

In a standard history or physical examination, there are no particular features indicating nerve entrapment. Absolute indications for humeral shaft fractures with radial palsy are limited to open fractures, vascular injuries, and unacceptable fracture alignment. Relative indications are polytrauma and secondary palsy after attempted fracture reduction. For all other humeral shaft fractures with radial nerve palsy, observation is still the mainstay of treatment, with spontaneous recovery occurring in up to 90% of patients.^2,8-12 Our patient did not have an absolute indication for operative treatment; surgery was nevertheless performed to address the polytrauma and to facilitate earlier mobilization.

Electromyelogram (EMG) studies typically are not useful after acute injury. EMG studies are better used serially to evaluate reinnervation after the acute phase. Bodner and colleagues^13,14 used ultrasonography to identify the radial nerve in a patient with unimproved radial nerve palsy 6 weeks after humeral shaft fracture. They found the nerve within the fracture site, whereas magnetic resonance imaging (MRI) could not follow its course. Neither ultrasonography nor MRI would likely be used after acute injury. More research is needed to improve evaluation of patients with continued palsy after nonoperative treatment.

In the case of our patient’s humeral shaft fracture, surgery was performed early because of polytrauma and radial nerve entrapment. If left interposed between 2 fracture fragments, the nerve would have been subjected to continued ischemia and likely would not have recovered spontaneously. Ikeda and Osamura⁷ reported on a case of radial nerve palsy that occurred after humerus shaft fracture. The nerve, entrapped between fracture fragments, was explored later, after function failed to return. As it was found within callus, the nerve was cut and then repaired end-to-end. In our patient’s case, early exploration led to release of the radial nerve from the fracture site—preventing irreversible nerve damage and allowing for spontaneous recovery over subsequent months.

Surgery for polytrauma patients with a humeral shaft fracture and radial nerve palsy may also be beneficial with respect to early nerve exploration and early mobilization. Although our patient’s fracture was well aligned and as an isolated injury would not have required surgery, the polytrauma called for early surgical management, which revealed radial nerve entrapment and led to early recovery of nerve function.

A radial nerve injury in association with a humeral shaft fracture is not an infrequent occurrence.^1,2 The nerve injury typically is thought to be a neurapraxia caused by a contusion, as spontaneous recovery rates range from 70% to 90%.^2-4 In cases in which acute nerve exploration and open reduction and internal fixation (ORIF) are not indicated, patient and clinician wait months for the nerve to recover. In some conservatively treated cases, the nerve is lacerated or entrapped. Patients with a lacerated or entrapped nerve may have better outcomes with early operative management.

We report on a rare case of the radial nerve entrapped within a nondisplaced segment of a closed humeral shaft fracture and describe the clinical outcome of early operative management. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An intoxicated, restrained 18-year-old driver in a motor vehicle collision sustained multiple injuries, including rib fracture, apical pneumothorax with pulmonary contusion, and corneal abrasion. Orthopedic injuries included right subtrochanteric femur fracture and midshaft right humeral shaft fracture (Figure 1).

Initial orthopedic evaluation of the right arm revealed decreased sensation in the radial nerve distribution. Motor function in the radial nerve was absent; the patient was incapable of active wrist extension or finger extension. Median and ulnar nerves were motor- and sensory-intact. Radiographs showed a displaced transverse midshaft humeral shaft fracture with a minimally displaced vertical fracture line extending from the fracture site about 3 cm into the proximal segment. The patient was placed in a coaptation splint. The femur fracture was treated with an antegrade piriformis entry intramedullary nail.

ORIF of the humerus was performed to facilitate mobilization of this polytrauma patient. He was positioned prone on a flat-top table with his right arm over a radiolucent extension. The arm was abducted at the shoulder and the elbow flexed. A posterior midline skin incision was made to reflect the triceps in a lateral-to-medial direction, facilitating dissection of the lateral brachial cutaneous nerve on the lateral aspect of the triceps, with resultant localization of the radial nerve. At that time, the radial nerve was noted to be entrapped in the fracture site (Figure 2). In the proximal segment was a sagittal split, displaced about 1 mm, and it was in this interval the nerve was held. This sagittal fracture appeared incomplete as it was followed more proximally. A unicortical Kirschner wire was placed in a posterior-to-anterior direction in each fragment alongside the nerve. A lamina spreader engaged the wires and distracted the fracture site as the tines were spread apart, releasing the nerve (Figure 3). The nerve was in continuity but was severely contused at that location. After the sagittal split was reduced, two 2.7-mm lag screws were used in lag fashion, and the transverse midshaft component was fixed with a 10-hole, 4.5-mm narrow locking compression plate. The radial nerve lay on the posterior aspect of the plate, between holes 4 and 5 (Figures 4, 5). The wound was closed, and the patient was made weight-bearing as tolerated in the right upper extremity. He was sent to occupational therapy, and static and dynamic splints were made for his wrist and hand.

Two months after injury, radial nerve examination findings were unchanged: decreased sensation on dorsum of hand and no motor function. At 3 months, electrodiagnostic testing showed neurophysiologic evidence of severe right radial neuropathy proximal to the innervation of the right brachioradialis. There were electrodiagnostic signs of ongoing axonal loss and no signs of ongoing reinnervation. At 4 months, only motor strength in wrist extension was improved (2/5). At 5 months, the patient had 4–/5 wrist extension, 3/5 metacarpophalangeal (MCP) extension of fingers, and 0/5 MCP/interphalangeal extension of thumb. Sensation in the radial nerve distribution was still decreased. At 7 months, strength in wrist extension and finger MCP extension was 4+/5. The fracture was now well healed, with maintained alignment and no changes in hardware appearance.

Discussion

In most cases, closed treatment of a humeral shaft fracture with an associated radial nerve injury has a successful outcome.⁵ The etiology of the neurapraxia likely is nerve contusion after the fracture. A neurapraxia is by definition a temporary injury to the myelin sheath with an intact nerve; the nerve function recovers rapidly.

Some humeral shaft fractures, however, have been associated with radial nerve injuries more severe than contusions, resulting in axonotmesis or neurotmesis. These more severe injuries make up 10% to 30% of humeral shaft fractures, including those with a frank laceration of the nerve and those with an entrapped nerve.^2,3 Shao and colleagues² reported a 90% recovery rate for patients who delayed extrication of the entrapped radial nerve. Although there is no consensus on timing of surgical exploration, motor and sensory function of the nerve is temporally related, which may indicate that earlier diagnosis and treatment lead to improved outcome.^6,7 Loss of radial nerve function can have devastating effects on upper extremity function. Often, patients lose all or some extension of the wrist and fingers and abduction and extension of the thumb.

In a standard history or physical examination, there are no particular features indicating nerve entrapment. Absolute indications for humeral shaft fractures with radial palsy are limited to open fractures, vascular injuries, and unacceptable fracture alignment. Relative indications are polytrauma and secondary palsy after attempted fracture reduction. For all other humeral shaft fractures with radial nerve palsy, observation is still the mainstay of treatment, with spontaneous recovery occurring in up to 90% of patients.^2,8-12 Our patient did not have an absolute indication for operative treatment; surgery was nevertheless performed to address the polytrauma and to facilitate earlier mobilization.

Electromyelogram (EMG) studies typically are not useful after acute injury. EMG studies are better used serially to evaluate reinnervation after the acute phase. Bodner and colleagues^13,14 used ultrasonography to identify the radial nerve in a patient with unimproved radial nerve palsy 6 weeks after humeral shaft fracture. They found the nerve within the fracture site, whereas magnetic resonance imaging (MRI) could not follow its course. Neither ultrasonography nor MRI would likely be used after acute injury. More research is needed to improve evaluation of patients with continued palsy after nonoperative treatment.

In the case of our patient’s humeral shaft fracture, surgery was performed early because of polytrauma and radial nerve entrapment. If left interposed between 2 fracture fragments, the nerve would have been subjected to continued ischemia and likely would not have recovered spontaneously. Ikeda and Osamura⁷ reported on a case of radial nerve palsy that occurred after humerus shaft fracture. The nerve, entrapped between fracture fragments, was explored later, after function failed to return. As it was found within callus, the nerve was cut and then repaired end-to-end. In our patient’s case, early exploration led to release of the radial nerve from the fracture site—preventing irreversible nerve damage and allowing for spontaneous recovery over subsequent months.

Surgery for polytrauma patients with a humeral shaft fracture and radial nerve palsy may also be beneficial with respect to early nerve exploration and early mobilization. Although our patient’s fracture was well aligned and as an isolated injury would not have required surgery, the polytrauma called for early surgical management, which revealed radial nerve entrapment and led to early recovery of nerve function.

A radial nerve injury in association with a humeral shaft fracture is not an infrequent occurrence.^1,2 The nerve injury typically is thought to be a neurapraxia caused by a contusion, as spontaneous recovery rates range from 70% to 90%.^2-4 In cases in which acute nerve exploration and open reduction and internal fixation (ORIF) are not indicated, patient and clinician wait months for the nerve to recover. In some conservatively treated cases, the nerve is lacerated or entrapped. Patients with a lacerated or entrapped nerve may have better outcomes with early operative management.

We report on a rare case of the radial nerve entrapped within a nondisplaced segment of a closed humeral shaft fracture and describe the clinical outcome of early operative management. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An intoxicated, restrained 18-year-old driver in a motor vehicle collision sustained multiple injuries, including rib fracture, apical pneumothorax with pulmonary contusion, and corneal abrasion. Orthopedic injuries included right subtrochanteric femur fracture and midshaft right humeral shaft fracture (Figure 1).

Initial orthopedic evaluation of the right arm revealed decreased sensation in the radial nerve distribution. Motor function in the radial nerve was absent; the patient was incapable of active wrist extension or finger extension. Median and ulnar nerves were motor- and sensory-intact. Radiographs showed a displaced transverse midshaft humeral shaft fracture with a minimally displaced vertical fracture line extending from the fracture site about 3 cm into the proximal segment. The patient was placed in a coaptation splint. The femur fracture was treated with an antegrade piriformis entry intramedullary nail.

ORIF of the humerus was performed to facilitate mobilization of this polytrauma patient. He was positioned prone on a flat-top table with his right arm over a radiolucent extension. The arm was abducted at the shoulder and the elbow flexed. A posterior midline skin incision was made to reflect the triceps in a lateral-to-medial direction, facilitating dissection of the lateral brachial cutaneous nerve on the lateral aspect of the triceps, with resultant localization of the radial nerve. At that time, the radial nerve was noted to be entrapped in the fracture site (Figure 2). In the proximal segment was a sagittal split, displaced about 1 mm, and it was in this interval the nerve was held. This sagittal fracture appeared incomplete as it was followed more proximally. A unicortical Kirschner wire was placed in a posterior-to-anterior direction in each fragment alongside the nerve. A lamina spreader engaged the wires and distracted the fracture site as the tines were spread apart, releasing the nerve (Figure 3). The nerve was in continuity but was severely contused at that location. After the sagittal split was reduced, two 2.7-mm lag screws were used in lag fashion, and the transverse midshaft component was fixed with a 10-hole, 4.5-mm narrow locking compression plate. The radial nerve lay on the posterior aspect of the plate, between holes 4 and 5 (Figures 4, 5). The wound was closed, and the patient was made weight-bearing as tolerated in the right upper extremity. He was sent to occupational therapy, and static and dynamic splints were made for his wrist and hand.

Two months after injury, radial nerve examination findings were unchanged: decreased sensation on dorsum of hand and no motor function. At 3 months, electrodiagnostic testing showed neurophysiologic evidence of severe right radial neuropathy proximal to the innervation of the right brachioradialis. There were electrodiagnostic signs of ongoing axonal loss and no signs of ongoing reinnervation. At 4 months, only motor strength in wrist extension was improved (2/5). At 5 months, the patient had 4–/5 wrist extension, 3/5 metacarpophalangeal (MCP) extension of fingers, and 0/5 MCP/interphalangeal extension of thumb. Sensation in the radial nerve distribution was still decreased. At 7 months, strength in wrist extension and finger MCP extension was 4+/5. The fracture was now well healed, with maintained alignment and no changes in hardware appearance.

Discussion

In most cases, closed treatment of a humeral shaft fracture with an associated radial nerve injury has a successful outcome.⁵ The etiology of the neurapraxia likely is nerve contusion after the fracture. A neurapraxia is by definition a temporary injury to the myelin sheath with an intact nerve; the nerve function recovers rapidly.

Some humeral shaft fractures, however, have been associated with radial nerve injuries more severe than contusions, resulting in axonotmesis or neurotmesis. These more severe injuries make up 10% to 30% of humeral shaft fractures, including those with a frank laceration of the nerve and those with an entrapped nerve.^2,3 Shao and colleagues² reported a 90% recovery rate for patients who delayed extrication of the entrapped radial nerve. Although there is no consensus on timing of surgical exploration, motor and sensory function of the nerve is temporally related, which may indicate that earlier diagnosis and treatment lead to improved outcome.^6,7 Loss of radial nerve function can have devastating effects on upper extremity function. Often, patients lose all or some extension of the wrist and fingers and abduction and extension of the thumb.

In a standard history or physical examination, there are no particular features indicating nerve entrapment. Absolute indications for humeral shaft fractures with radial palsy are limited to open fractures, vascular injuries, and unacceptable fracture alignment. Relative indications are polytrauma and secondary palsy after attempted fracture reduction. For all other humeral shaft fractures with radial nerve palsy, observation is still the mainstay of treatment, with spontaneous recovery occurring in up to 90% of patients.^2,8-12 Our patient did not have an absolute indication for operative treatment; surgery was nevertheless performed to address the polytrauma and to facilitate earlier mobilization.

Electromyelogram (EMG) studies typically are not useful after acute injury. EMG studies are better used serially to evaluate reinnervation after the acute phase. Bodner and colleagues^13,14 used ultrasonography to identify the radial nerve in a patient with unimproved radial nerve palsy 6 weeks after humeral shaft fracture. They found the nerve within the fracture site, whereas magnetic resonance imaging (MRI) could not follow its course. Neither ultrasonography nor MRI would likely be used after acute injury. More research is needed to improve evaluation of patients with continued palsy after nonoperative treatment.

In the case of our patient’s humeral shaft fracture, surgery was performed early because of polytrauma and radial nerve entrapment. If left interposed between 2 fracture fragments, the nerve would have been subjected to continued ischemia and likely would not have recovered spontaneously. Ikeda and Osamura⁷ reported on a case of radial nerve palsy that occurred after humerus shaft fracture. The nerve, entrapped between fracture fragments, was explored later, after function failed to return. As it was found within callus, the nerve was cut and then repaired end-to-end. In our patient’s case, early exploration led to release of the radial nerve from the fracture site—preventing irreversible nerve damage and allowing for spontaneous recovery over subsequent months.

Surgery for polytrauma patients with a humeral shaft fracture and radial nerve palsy may also be beneficial with respect to early nerve exploration and early mobilization. Although our patient’s fracture was well aligned and as an isolated injury would not have required surgery, the polytrauma called for early surgical management, which revealed radial nerve entrapment and led to early recovery of nerve function.

Body mass index (BMI) is thought to be a predictor of body composition, with higher values indicating more adipose tissue. BMI is a measure of mass with respect to height. The World Health Organization¹ has established health categories based on BMI measurements. Values from 18.5 to 24.9 kg/m² are deemed to represent normal weight; those from 25 to 30 kg/m², overweight; and those higher than 30 kg/m², obesity. BMI is not a perfect tool, but it is the most widely used tool in clinical and research practice because of its relative reliability and ease of use.² Being overweight or obese (according to BMI) is increasingly common among adults worldwide, and particularly in the United States. An estimated 39% of adults worldwide are overweight, and 13% are obese.¹ An estimated 69% of US adults are overweight, including 35.1% who are obese.²

Various pathologies have been treated with reverse shoulder arthroplasty (RSA), and results have been promising,^3-9 but little is known about patient demographic and clinical factors that may adversely affect outcomes. Recent work suggests younger age⁷ and failed prior arthroplasty may adversely affect RSA outcomes.¹⁰ Higher BMI has also been implicated as a cause of increased perioperative and immediate postoperative complications of RSA with minimum 90-day follow-up, but no one has examined shoulder function scores at minimum 2-year follow-up.^11,12

We conducted a study to examine shoulder function scores, mobility, patient satisfaction, and complications at minimum 2-year follow-up in normal-weight, overweight, and obese patients who underwent RSA. We hypothesized that, compared with normal-weight patients, obese patients would have worse shoulder function scores, worse mobility, and more complications.

Materials and Methods

Inclusion Criteria and Demographics

After obtaining Institutional Review Board approval for this study, we used a prospective shoulder arthroplasty registry to identify patients (N = 77) who had rotator cuff tear arthropathy (RCTA) treated with primary RSA and then had minimum 2-year follow-up. The study period was 2004-2011. All patients had RCTA diagnosed with physical examination findings and anteroposterior, scapular Y, and axillary radiographs. RCTA was graded 1 to 5 using the classification system of Hamada and colleagues.¹³ Rotator cuff status was determined with preoperative computed tomography arthrogram (CTA) or magnetic resonance imaging (MRI) and confirmed at time of surgery. BMI calculations were based on height and weight measured at initial office visit. Thirty-four patients had normal weight (BMI <25 kg/m²), 21 were overweight (BMI 25-30 kg/m²), and 22 were obese (BMI >30 kg/m²). Patient demographic and clinical characteristics reviewed also included age, sex, follow-up duration, arm dominance, complications, prevalence of depression, and prevalence of diabetes. All RSAs were performed by the same surgeon (Dr. Edwards) at a single high-volume shoulder arthroplasty center.

Shoulder function scores evaluated before surgery and at final follow-up included Constant score,¹⁴ American Shoulder and Elbow Surgeons (ASES) score,¹⁵ Western Ontario Osteoarthritis Shoulder (WOOS) index,¹⁶ Single Assessment Numeric Evaluation (SANE),¹⁷ and mobility. Satisfaction was assessed by having patients describe themselves as very dissatisfied, dissatisfied, satisfied, or very satisfied. All intraoperative and postoperative complications were recorded.

Surgical Technique and Postoperative Rehabilitation

The Aequalis RSA system (Tornier) was used for all patients during the study period. The RSA technique used has been well described.^18,19 A standard postoperative rehabilitation protocol was followed.^19,20

Clinical and Radiographic Assessment

Patients were prospectively enrolled in a shoulder arthroplasty outcomes registry and followed clinically. Mean follow-up was 3.16 years (range, 2-8 years). Before surgery, patients were examined by the surgeon. Examinations were repeated 1 week, 6 weeks, 3 months, 6 months, and 12 months after surgery and annually thereafter. Mobility (active range of motion) was determined with a handheld goniometer. Strength of abduction was measured with a handheld digital dynamometer (Chatillon digital force gauge, 200 lbf; Ametek). Anteroposterior in plane of scapula, scapular Y, and axillary radiographs were obtained at each clinic appointment.

Before surgery, the surgeon reviewed all radiographs. Each RCTA was given a Hamada grade (1-5).¹³ Glenoid erosion in the coronal plane was classified (E0, E1, E2, E3) according to Sirveaux and colleagues.²¹ Hamada grades and glenoid erosion types are listed in Table 1. The overall trend in classification by BMI group was statistically significant for Hamada grade (P = .004) but not glenoid erosion type (P = .153).

Before surgery, the surgeon also evaluated rotator cuff status using CTA or MRI. All patients had full-thickness tears of the supraspinatus and infraspinatus. The subscapularis was variably present, and subscapularis repair was performed when the subscapularis was intact. Rotator cuff status is listed in Table 2. There were no significant differences in the distribution of intact subscapularis (P = .402) or teres minor (P = .188) among the normal-weight, overweight, and obese groups. No patient had a latissimus dorsi transfer at time of RSA.

Statistical Analysis

Independent-samples t tests assuming unequal variances were used to compare the 3 BMI groups on age, follow-up duration, preoperative shoulder function scores, and mobility. Chi-square tests were used to identify any significant group differences in comorbidities (eg, complications, arm dominance, prevalence of depression, prevalence of diabetes) and patient satisfaction. Repeated-measures analysis of variance was used to evaluate main effects, changes from before surgery to final follow-up, and BMI group differences, as well as differences in changes from before surgery to final follow-up among the 3 BMI groups.

Results

Among BMI groups (<25 kg/m², 25-30 kg/m², >30 kg/m²), there were no statistically significant preoperative differences in age, sex, follow-up duration, complications, arm dominance, prevalence of depression, or prevalence of diabetes (P >. 05) (Table 3). Table 4 lists the groups’ preoperative and final follow-up data (Constant score, ASES score, WOOS index, SANE, mobility). There were no statistically significant preoperative group differences in Constant score, ASES score, WOOS index, SANE, mobility, or patient satisfaction (P > .05) (Tables 5, 6).

All groups’ shoulder function scores and mobility improved significantly from before surgery to final follow-up (P < .001) (Table 5). The groups’ magnitudes of change (improvement) from before surgery to final follow-up were almost identical, with no significant differences in shoulder function scores or mobility (Table 5). The only significant difference was in Constant–Strength, which was higher in the obese group (P = .017) (Table 5). Patient satisfaction ratings improved after surgery, with 79% of the normal-weight group reporting being satisfied or very satisfied with their shoulders (Table 6). The overweight and obese groups gave similar satisfied (81%) and very satisfied (82%) ratings. The small differences between group satisfaction scores were nonsignificant (P = .967).

Complications

The normal-weight group had 4 complications: periprosthetic infection (2 cases), intraoperative humeral fracture (1), and scapular spine stress fracture (1). The overweight group had 1 complication, an acromial stress fracture that was successfully treated with conservative measures. The obese group had 1 patient with 2 postoperative dislocations. The first dislocation was treated with closed reduction and bracing, and the second required revision surgery. There was no statistical difference in complications among the groups (P = .680).

Discussion

To our knowledge, this is the first study of the effects of varying BMI on functional outcomes of RSA with minimum 2-year follow-up. There appears to be minimal impact on shoulder function scores, complications, and patient satisfaction among normal-weight, overweight, and obese patients with RCTA treated by the same surgeon using similar techniques.

The relationship between obesity and increased perioperative risks or poorer surgical outcomes has been well established in orthopedic surgery. In a systematic review, Falagas and Kompoti²² found increased risk for perioperative and nosocomial infections in obese patients. Schoenfeld and colleagues²³ and Jiang and colleagues²⁴ reported increased risk for complications in spinal surgery. The total joint arthroplasty literature is rife with evidence suggesting higher BMI leads to increased risk for complications, including infection and deep venous thrombosis, as well as decreased functional outcome scores.^25-29 Recent studies on shoulder surgery have shown worse outcomes in rotator cuff repair³⁰ and a higher revision rate in hemiarthroplasy.³¹

Other RSA studies have examined short-term complications or perioperative risk factors associated with BMI. In a study using slightly different BMI groupings, Gupta and colleagues¹² reported significantly higher complication rates for RSA patients with BMI higher than 35 kg/m² compared to patients with BMI of 25 to 35 kg/m² and compared to patients with BMI lower than 25 kg/m². Their study highlighted medical and surgical complications and used a short follow-up period (minimum, 90 days). It did not assess shoulder function scores, and included multiple indications for RSA (eg, RCTA, proximal humerus fracture, inflammatory arthropathy). In another study, higher BMI was reported as a risk factor for early dislocation after RSA, but only 11 patients with a history of dislocation were assessed, and minimum follow-up was 6 months.³² We know of only one study that addressed RSA outcomes in obese patients and used minimum 2-year follow-up, but its primary endpoint was rate of complications, and it did not report shoulder function scores.¹¹ Li and colleagues³³ conducted a study similar to ours, but with primary total shoulder arthroplasty (TSA) patients, and reported similar results. Relative to normal BMI, higher BMI did not have a detrimental effect on short-term improvement in shoulder function after TSA.

Given the US obesity epidemic, our study results are encouraging. Depending on many factors, obesity remains a risk factor for poor outcomes in patients who undergo orthopedic surgery. As our results show, however, patients with higher BMI can obtain functional outcomes similar to those experienced by patients with normal-weight BMI after RSA for RCTA.

The primary limitation of this study was its retrospective design. Strengths of the study included its having a single surgeon and a single diagnosis: RCTA. In addition, each group was robust in size, a standard operative/postoperative protocol was used, and clinical results were measured with multiple validated shoulder function scores.

Conclusion

Improved shoulder function scores, mobility, and patient satisfaction can be expected after RSA for RCTA in patients with BMI higher than 30 kg/m². These patients did not exhibit an increase in complications at short-term follow-up.

Body mass index (BMI) is thought to be a predictor of body composition, with higher values indicating more adipose tissue. BMI is a measure of mass with respect to height. The World Health Organization¹ has established health categories based on BMI measurements. Values from 18.5 to 24.9 kg/m² are deemed to represent normal weight; those from 25 to 30 kg/m², overweight; and those higher than 30 kg/m², obesity. BMI is not a perfect tool, but it is the most widely used tool in clinical and research practice because of its relative reliability and ease of use.² Being overweight or obese (according to BMI) is increasingly common among adults worldwide, and particularly in the United States. An estimated 39% of adults worldwide are overweight, and 13% are obese.¹ An estimated 69% of US adults are overweight, including 35.1% who are obese.²

Various pathologies have been treated with reverse shoulder arthroplasty (RSA), and results have been promising,^3-9 but little is known about patient demographic and clinical factors that may adversely affect outcomes. Recent work suggests younger age⁷ and failed prior arthroplasty may adversely affect RSA outcomes.¹⁰ Higher BMI has also been implicated as a cause of increased perioperative and immediate postoperative complications of RSA with minimum 90-day follow-up, but no one has examined shoulder function scores at minimum 2-year follow-up.^11,12

We conducted a study to examine shoulder function scores, mobility, patient satisfaction, and complications at minimum 2-year follow-up in normal-weight, overweight, and obese patients who underwent RSA. We hypothesized that, compared with normal-weight patients, obese patients would have worse shoulder function scores, worse mobility, and more complications.

Materials and Methods

Inclusion Criteria and Demographics

After obtaining Institutional Review Board approval for this study, we used a prospective shoulder arthroplasty registry to identify patients (N = 77) who had rotator cuff tear arthropathy (RCTA) treated with primary RSA and then had minimum 2-year follow-up. The study period was 2004-2011. All patients had RCTA diagnosed with physical examination findings and anteroposterior, scapular Y, and axillary radiographs. RCTA was graded 1 to 5 using the classification system of Hamada and colleagues.¹³ Rotator cuff status was determined with preoperative computed tomography arthrogram (CTA) or magnetic resonance imaging (MRI) and confirmed at time of surgery. BMI calculations were based on height and weight measured at initial office visit. Thirty-four patients had normal weight (BMI <25 kg/m²), 21 were overweight (BMI 25-30 kg/m²), and 22 were obese (BMI >30 kg/m²). Patient demographic and clinical characteristics reviewed also included age, sex, follow-up duration, arm dominance, complications, prevalence of depression, and prevalence of diabetes. All RSAs were performed by the same surgeon (Dr. Edwards) at a single high-volume shoulder arthroplasty center.

Shoulder function scores evaluated before surgery and at final follow-up included Constant score,¹⁴ American Shoulder and Elbow Surgeons (ASES) score,¹⁵ Western Ontario Osteoarthritis Shoulder (WOOS) index,¹⁶ Single Assessment Numeric Evaluation (SANE),¹⁷ and mobility. Satisfaction was assessed by having patients describe themselves as very dissatisfied, dissatisfied, satisfied, or very satisfied. All intraoperative and postoperative complications were recorded.

Surgical Technique and Postoperative Rehabilitation

The Aequalis RSA system (Tornier) was used for all patients during the study period. The RSA technique used has been well described.^18,19 A standard postoperative rehabilitation protocol was followed.^19,20

Clinical and Radiographic Assessment

Patients were prospectively enrolled in a shoulder arthroplasty outcomes registry and followed clinically. Mean follow-up was 3.16 years (range, 2-8 years). Before surgery, patients were examined by the surgeon. Examinations were repeated 1 week, 6 weeks, 3 months, 6 months, and 12 months after surgery and annually thereafter. Mobility (active range of motion) was determined with a handheld goniometer. Strength of abduction was measured with a handheld digital dynamometer (Chatillon digital force gauge, 200 lbf; Ametek). Anteroposterior in plane of scapula, scapular Y, and axillary radiographs were obtained at each clinic appointment.

Before surgery, the surgeon reviewed all radiographs. Each RCTA was given a Hamada grade (1-5).¹³ Glenoid erosion in the coronal plane was classified (E0, E1, E2, E3) according to Sirveaux and colleagues.²¹ Hamada grades and glenoid erosion types are listed in Table 1. The overall trend in classification by BMI group was statistically significant for Hamada grade (P = .004) but not glenoid erosion type (P = .153).

Before surgery, the surgeon also evaluated rotator cuff status using CTA or MRI. All patients had full-thickness tears of the supraspinatus and infraspinatus. The subscapularis was variably present, and subscapularis repair was performed when the subscapularis was intact. Rotator cuff status is listed in Table 2. There were no significant differences in the distribution of intact subscapularis (P = .402) or teres minor (P = .188) among the normal-weight, overweight, and obese groups. No patient had a latissimus dorsi transfer at time of RSA.

Statistical Analysis

Independent-samples t tests assuming unequal variances were used to compare the 3 BMI groups on age, follow-up duration, preoperative shoulder function scores, and mobility. Chi-square tests were used to identify any significant group differences in comorbidities (eg, complications, arm dominance, prevalence of depression, prevalence of diabetes) and patient satisfaction. Repeated-measures analysis of variance was used to evaluate main effects, changes from before surgery to final follow-up, and BMI group differences, as well as differences in changes from before surgery to final follow-up among the 3 BMI groups.

Results

Among BMI groups (<25 kg/m², 25-30 kg/m², >30 kg/m²), there were no statistically significant preoperative differences in age, sex, follow-up duration, complications, arm dominance, prevalence of depression, or prevalence of diabetes (P >. 05) (Table 3). Table 4 lists the groups’ preoperative and final follow-up data (Constant score, ASES score, WOOS index, SANE, mobility). There were no statistically significant preoperative group differences in Constant score, ASES score, WOOS index, SANE, mobility, or patient satisfaction (P > .05) (Tables 5, 6).

All groups’ shoulder function scores and mobility improved significantly from before surgery to final follow-up (P < .001) (Table 5). The groups’ magnitudes of change (improvement) from before surgery to final follow-up were almost identical, with no significant differences in shoulder function scores or mobility (Table 5). The only significant difference was in Constant–Strength, which was higher in the obese group (P = .017) (Table 5). Patient satisfaction ratings improved after surgery, with 79% of the normal-weight group reporting being satisfied or very satisfied with their shoulders (Table 6). The overweight and obese groups gave similar satisfied (81%) and very satisfied (82%) ratings. The small differences between group satisfaction scores were nonsignificant (P = .967).

Complications

The normal-weight group had 4 complications: periprosthetic infection (2 cases), intraoperative humeral fracture (1), and scapular spine stress fracture (1). The overweight group had 1 complication, an acromial stress fracture that was successfully treated with conservative measures. The obese group had 1 patient with 2 postoperative dislocations. The first dislocation was treated with closed reduction and bracing, and the second required revision surgery. There was no statistical difference in complications among the groups (P = .680).

Discussion

To our knowledge, this is the first study of the effects of varying BMI on functional outcomes of RSA with minimum 2-year follow-up. There appears to be minimal impact on shoulder function scores, complications, and patient satisfaction among normal-weight, overweight, and obese patients with RCTA treated by the same surgeon using similar techniques.

The relationship between obesity and increased perioperative risks or poorer surgical outcomes has been well established in orthopedic surgery. In a systematic review, Falagas and Kompoti²² found increased risk for perioperative and nosocomial infections in obese patients. Schoenfeld and colleagues²³ and Jiang and colleagues²⁴ reported increased risk for complications in spinal surgery. The total joint arthroplasty literature is rife with evidence suggesting higher BMI leads to increased risk for complications, including infection and deep venous thrombosis, as well as decreased functional outcome scores.^25-29 Recent studies on shoulder surgery have shown worse outcomes in rotator cuff repair³⁰ and a higher revision rate in hemiarthroplasy.³¹

Other RSA studies have examined short-term complications or perioperative risk factors associated with BMI. In a study using slightly different BMI groupings, Gupta and colleagues¹² reported significantly higher complication rates for RSA patients with BMI higher than 35 kg/m² compared to patients with BMI of 25 to 35 kg/m² and compared to patients with BMI lower than 25 kg/m². Their study highlighted medical and surgical complications and used a short follow-up period (minimum, 90 days). It did not assess shoulder function scores, and included multiple indications for RSA (eg, RCTA, proximal humerus fracture, inflammatory arthropathy). In another study, higher BMI was reported as a risk factor for early dislocation after RSA, but only 11 patients with a history of dislocation were assessed, and minimum follow-up was 6 months.³² We know of only one study that addressed RSA outcomes in obese patients and used minimum 2-year follow-up, but its primary endpoint was rate of complications, and it did not report shoulder function scores.¹¹ Li and colleagues³³ conducted a study similar to ours, but with primary total shoulder arthroplasty (TSA) patients, and reported similar results. Relative to normal BMI, higher BMI did not have a detrimental effect on short-term improvement in shoulder function after TSA.

Given the US obesity epidemic, our study results are encouraging. Depending on many factors, obesity remains a risk factor for poor outcomes in patients who undergo orthopedic surgery. As our results show, however, patients with higher BMI can obtain functional outcomes similar to those experienced by patients with normal-weight BMI after RSA for RCTA.

The primary limitation of this study was its retrospective design. Strengths of the study included its having a single surgeon and a single diagnosis: RCTA. In addition, each group was robust in size, a standard operative/postoperative protocol was used, and clinical results were measured with multiple validated shoulder function scores.

Conclusion

Improved shoulder function scores, mobility, and patient satisfaction can be expected after RSA for RCTA in patients with BMI higher than 30 kg/m². These patients did not exhibit an increase in complications at short-term follow-up.

Body mass index (BMI) is thought to be a predictor of body composition, with higher values indicating more adipose tissue. BMI is a measure of mass with respect to height. The World Health Organization¹ has established health categories based on BMI measurements. Values from 18.5 to 24.9 kg/m² are deemed to represent normal weight; those from 25 to 30 kg/m², overweight; and those higher than 30 kg/m², obesity. BMI is not a perfect tool, but it is the most widely used tool in clinical and research practice because of its relative reliability and ease of use.² Being overweight or obese (according to BMI) is increasingly common among adults worldwide, and particularly in the United States. An estimated 39% of adults worldwide are overweight, and 13% are obese.¹ An estimated 69% of US adults are overweight, including 35.1% who are obese.²

Various pathologies have been treated with reverse shoulder arthroplasty (RSA), and results have been promising,^3-9 but little is known about patient demographic and clinical factors that may adversely affect outcomes. Recent work suggests younger age⁷ and failed prior arthroplasty may adversely affect RSA outcomes.¹⁰ Higher BMI has also been implicated as a cause of increased perioperative and immediate postoperative complications of RSA with minimum 90-day follow-up, but no one has examined shoulder function scores at minimum 2-year follow-up.^11,12

We conducted a study to examine shoulder function scores, mobility, patient satisfaction, and complications at minimum 2-year follow-up in normal-weight, overweight, and obese patients who underwent RSA. We hypothesized that, compared with normal-weight patients, obese patients would have worse shoulder function scores, worse mobility, and more complications.

Materials and Methods

Inclusion Criteria and Demographics

After obtaining Institutional Review Board approval for this study, we used a prospective shoulder arthroplasty registry to identify patients (N = 77) who had rotator cuff tear arthropathy (RCTA) treated with primary RSA and then had minimum 2-year follow-up. The study period was 2004-2011. All patients had RCTA diagnosed with physical examination findings and anteroposterior, scapular Y, and axillary radiographs. RCTA was graded 1 to 5 using the classification system of Hamada and colleagues.¹³ Rotator cuff status was determined with preoperative computed tomography arthrogram (CTA) or magnetic resonance imaging (MRI) and confirmed at time of surgery. BMI calculations were based on height and weight measured at initial office visit. Thirty-four patients had normal weight (BMI <25 kg/m²), 21 were overweight (BMI 25-30 kg/m²), and 22 were obese (BMI >30 kg/m²). Patient demographic and clinical characteristics reviewed also included age, sex, follow-up duration, arm dominance, complications, prevalence of depression, and prevalence of diabetes. All RSAs were performed by the same surgeon (Dr. Edwards) at a single high-volume shoulder arthroplasty center.

Shoulder function scores evaluated before surgery and at final follow-up included Constant score,¹⁴ American Shoulder and Elbow Surgeons (ASES) score,¹⁵ Western Ontario Osteoarthritis Shoulder (WOOS) index,¹⁶ Single Assessment Numeric Evaluation (SANE),¹⁷ and mobility. Satisfaction was assessed by having patients describe themselves as very dissatisfied, dissatisfied, satisfied, or very satisfied. All intraoperative and postoperative complications were recorded.

Surgical Technique and Postoperative Rehabilitation

The Aequalis RSA system (Tornier) was used for all patients during the study period. The RSA technique used has been well described.^18,19 A standard postoperative rehabilitation protocol was followed.^19,20

Clinical and Radiographic Assessment

Patients were prospectively enrolled in a shoulder arthroplasty outcomes registry and followed clinically. Mean follow-up was 3.16 years (range, 2-8 years). Before surgery, patients were examined by the surgeon. Examinations were repeated 1 week, 6 weeks, 3 months, 6 months, and 12 months after surgery and annually thereafter. Mobility (active range of motion) was determined with a handheld goniometer. Strength of abduction was measured with a handheld digital dynamometer (Chatillon digital force gauge, 200 lbf; Ametek). Anteroposterior in plane of scapula, scapular Y, and axillary radiographs were obtained at each clinic appointment.

Before surgery, the surgeon reviewed all radiographs. Each RCTA was given a Hamada grade (1-5).¹³ Glenoid erosion in the coronal plane was classified (E0, E1, E2, E3) according to Sirveaux and colleagues.²¹ Hamada grades and glenoid erosion types are listed in Table 1. The overall trend in classification by BMI group was statistically significant for Hamada grade (P = .004) but not glenoid erosion type (P = .153).

Before surgery, the surgeon also evaluated rotator cuff status using CTA or MRI. All patients had full-thickness tears of the supraspinatus and infraspinatus. The subscapularis was variably present, and subscapularis repair was performed when the subscapularis was intact. Rotator cuff status is listed in Table 2. There were no significant differences in the distribution of intact subscapularis (P = .402) or teres minor (P = .188) among the normal-weight, overweight, and obese groups. No patient had a latissimus dorsi transfer at time of RSA.

Statistical Analysis

Independent-samples t tests assuming unequal variances were used to compare the 3 BMI groups on age, follow-up duration, preoperative shoulder function scores, and mobility. Chi-square tests were used to identify any significant group differences in comorbidities (eg, complications, arm dominance, prevalence of depression, prevalence of diabetes) and patient satisfaction. Repeated-measures analysis of variance was used to evaluate main effects, changes from before surgery to final follow-up, and BMI group differences, as well as differences in changes from before surgery to final follow-up among the 3 BMI groups.

Results

Among BMI groups (<25 kg/m², 25-30 kg/m², >30 kg/m²), there were no statistically significant preoperative differences in age, sex, follow-up duration, complications, arm dominance, prevalence of depression, or prevalence of diabetes (P >. 05) (Table 3). Table 4 lists the groups’ preoperative and final follow-up data (Constant score, ASES score, WOOS index, SANE, mobility). There were no statistically significant preoperative group differences in Constant score, ASES score, WOOS index, SANE, mobility, or patient satisfaction (P > .05) (Tables 5, 6).

All groups’ shoulder function scores and mobility improved significantly from before surgery to final follow-up (P < .001) (Table 5). The groups’ magnitudes of change (improvement) from before surgery to final follow-up were almost identical, with no significant differences in shoulder function scores or mobility (Table 5). The only significant difference was in Constant–Strength, which was higher in the obese group (P = .017) (Table 5). Patient satisfaction ratings improved after surgery, with 79% of the normal-weight group reporting being satisfied or very satisfied with their shoulders (Table 6). The overweight and obese groups gave similar satisfied (81%) and very satisfied (82%) ratings. The small differences between group satisfaction scores were nonsignificant (P = .967).

Complications

The normal-weight group had 4 complications: periprosthetic infection (2 cases), intraoperative humeral fracture (1), and scapular spine stress fracture (1). The overweight group had 1 complication, an acromial stress fracture that was successfully treated with conservative measures. The obese group had 1 patient with 2 postoperative dislocations. The first dislocation was treated with closed reduction and bracing, and the second required revision surgery. There was no statistical difference in complications among the groups (P = .680).

Discussion

To our knowledge, this is the first study of the effects of varying BMI on functional outcomes of RSA with minimum 2-year follow-up. There appears to be minimal impact on shoulder function scores, complications, and patient satisfaction among normal-weight, overweight, and obese patients with RCTA treated by the same surgeon using similar techniques.

The relationship between obesity and increased perioperative risks or poorer surgical outcomes has been well established in orthopedic surgery. In a systematic review, Falagas and Kompoti²² found increased risk for perioperative and nosocomial infections in obese patients. Schoenfeld and colleagues²³ and Jiang and colleagues²⁴ reported increased risk for complications in spinal surgery. The total joint arthroplasty literature is rife with evidence suggesting higher BMI leads to increased risk for complications, including infection and deep venous thrombosis, as well as decreased functional outcome scores.^25-29 Recent studies on shoulder surgery have shown worse outcomes in rotator cuff repair³⁰ and a higher revision rate in hemiarthroplasy.³¹

Other RSA studies have examined short-term complications or perioperative risk factors associated with BMI. In a study using slightly different BMI groupings, Gupta and colleagues¹² reported significantly higher complication rates for RSA patients with BMI higher than 35 kg/m² compared to patients with BMI of 25 to 35 kg/m² and compared to patients with BMI lower than 25 kg/m². Their study highlighted medical and surgical complications and used a short follow-up period (minimum, 90 days). It did not assess shoulder function scores, and included multiple indications for RSA (eg, RCTA, proximal humerus fracture, inflammatory arthropathy). In another study, higher BMI was reported as a risk factor for early dislocation after RSA, but only 11 patients with a history of dislocation were assessed, and minimum follow-up was 6 months.³² We know of only one study that addressed RSA outcomes in obese patients and used minimum 2-year follow-up, but its primary endpoint was rate of complications, and it did not report shoulder function scores.¹¹ Li and colleagues³³ conducted a study similar to ours, but with primary total shoulder arthroplasty (TSA) patients, and reported similar results. Relative to normal BMI, higher BMI did not have a detrimental effect on short-term improvement in shoulder function after TSA.

Given the US obesity epidemic, our study results are encouraging. Depending on many factors, obesity remains a risk factor for poor outcomes in patients who undergo orthopedic surgery. As our results show, however, patients with higher BMI can obtain functional outcomes similar to those experienced by patients with normal-weight BMI after RSA for RCTA.

The primary limitation of this study was its retrospective design. Strengths of the study included its having a single surgeon and a single diagnosis: RCTA. In addition, each group was robust in size, a standard operative/postoperative protocol was used, and clinical results were measured with multiple validated shoulder function scores.

Conclusion

Improved shoulder function scores, mobility, and patient satisfaction can be expected after RSA for RCTA in patients with BMI higher than 30 kg/m². These patients did not exhibit an increase in complications at short-term follow-up.

ORLANDO, FL—Using arthroscopic superior capsule reconstruction (ASCR) to treat patients with massive rotator cuff tears can improve shoulder strength and function, according to research presented at the American Orthopedic Society for Sports Medicine’s Specialty Day.

Researchers used ASCR to treat 100 patients (average age: 66) who had irreparable rotator cuff tears that failed during previous treatment. Physical exams, x-rays, and magnetic resonance imaging were performed before surgery, at 3, 6 and 12 months following surgery, and on a yearly basis thereafter. Rates of return to work or sport were analyzed in 34 patients who were employed and 26 patients who were recreational athletes before the rotator cuff tear.

Overall, 92% of patients significantly improved their strength and shoulder function. In all, 32 patients returned fully to their previous work and 2 patients returned with reduced hours and workloads. All 26 patients who played sports prior to injury fully returned to their activities.

ORLANDO, FL—Using arthroscopic superior capsule reconstruction (ASCR) to treat patients with massive rotator cuff tears can improve shoulder strength and function, according to research presented at the American Orthopedic Society for Sports Medicine’s Specialty Day.

Researchers used ASCR to treat 100 patients (average age: 66) who had irreparable rotator cuff tears that failed during previous treatment. Physical exams, x-rays, and magnetic resonance imaging were performed before surgery, at 3, 6 and 12 months following surgery, and on a yearly basis thereafter. Rates of return to work or sport were analyzed in 34 patients who were employed and 26 patients who were recreational athletes before the rotator cuff tear.

Overall, 92% of patients significantly improved their strength and shoulder function. In all, 32 patients returned fully to their previous work and 2 patients returned with reduced hours and workloads. All 26 patients who played sports prior to injury fully returned to their activities.

ORLANDO, FL—Using arthroscopic superior capsule reconstruction (ASCR) to treat patients with massive rotator cuff tears can improve shoulder strength and function, according to research presented at the American Orthopedic Society for Sports Medicine’s Specialty Day.

Researchers used ASCR to treat 100 patients (average age: 66) who had irreparable rotator cuff tears that failed during previous treatment. Physical exams, x-rays, and magnetic resonance imaging were performed before surgery, at 3, 6 and 12 months following surgery, and on a yearly basis thereafter. Rates of return to work or sport were analyzed in 34 patients who were employed and 26 patients who were recreational athletes before the rotator cuff tear.

Overall, 92% of patients significantly improved their strength and shoulder function. In all, 32 patients returned fully to their previous work and 2 patients returned with reduced hours and workloads. All 26 patients who played sports prior to injury fully returned to their activities.

The musculoskeletal (MSK) ultrasound evaluation of the shoulder provides a cost- and time-efficient imaging modality with similar diagnostic power as magnetic resonance imaging (MRI).^1,2 Its portable point-of-care applications can be used in the office, in the operating room, and in sideline athletic event coverage, as we discussed in Part 1 of this series.³

MSK ultrasound may seem difficult and daunting, and many articles have quoted steep learning curves.^4,5 However, in our experience in teaching many ultrasound courses, this modality can be learned quite quickly with the proper instruction. Physicians are already familiar with anatomy and usually have had some exposure to MRI.⁴ Taking courses in MSK ultrasound or simply learning the basic concepts of ultrasound and then learning the machine controls is usually a good start.^5-8 Practice scanning normal individuals, comparing the images from an MRI to learn how to reproduce the same planes and images. This will allow the user to become familiar with normal anatomy and how to see the images on the ultrasound screen.^5-8 Vollman and colleagues⁹ showed that in trainees, combining MRI images with sonograms enhances the ability to correctly identify MSK ultrasound anatomy from 40.9% to 72.5%, when compared with learning from ultrasound images alone.

There are currently no certifications necessary to perform ultrasound scans or bill for them; however, some insurance carriers may require demonstrating relevant, documented training for reimbursement.³ Various organizations are trying to develop certifications and regulations for ultrasound to standardize the use of this modality. In the United States, the American Institute of Ultrasound in Medicine (AIUM) and the American Registry for Diagnostic Medical Sonography (ARDMS) provide guidelines and particular MSK ultrasound certifications.^10,11

Basic Ultrasound Principles

The ultrasound machine creates electrical impulses that are turned into sound waves by piezoelectric crystals at the probe’s footprint. These sound waves bounce off tissues and return to the probe, where they are converted electronically to an image on the monitor. Depending on the echogenicity of the scanned tissue, the ultrasound beam will either reflect or be absorbed at different rates. This variance is transmitted on the monitor as a grayscale image. When ultrasound waves are highly reflective, like in bone or fat, they are characterized as hyperechoic. The opposite occurs when ultrasound waves are absorbed like in the fluid of a cystic cavity or joint effusion, and the image appears black. This is described as anechoic.¹² Intermediate tissues such as tendons that are less reflective are seen as hypoechoic and appear gray. When a tissue has a similar echogenicity to its surrounding tissues, it is called isoechoic.¹²

The transducer is the scanning component of the ultrasound machine. Transducers come in 2 shapes: linear and curvilinear. The linear probe creates a straight image that is equal to the size of the transducer footprint. The curvilinear probe creates a wider, wedge-shaped panoramic image.

Linear probes are of higher frequency and generate higher resolution images of shallower structures, while curvilinear probes have greater depth penetration but generate lower resolution images. A high frequency of 10 to 15 MHz is preferred for anatomy between 2 cm to 4 cm depth.¹³ Midrange frequency of 5 to 10 MHz is preferred at 5 cm to 6 cm depth, and low-frequency 2 to 5 MHz probes are preferred for anatomical structures >6 cm depth.¹³

Anisotropy is the property of being directionally dependent, as opposed to isotropy, which implies identical properties in all directions. This anisotropic effect is dependent on the angle of the insonating beam. The maximum return echo occurs when the ultrasound beam is perpendicular to the tendon. Decreasing the insonating angle on a normal tendon will cause it to change from brightly hyperechoic (the actual echo from tightly bound tendon fibers) to darkly hypoechoic. If the angle is then increased, the tendon will again appear hyperechoic. If the artifact causes a normal tendon to appear hypoechoic, it may falsely lead to a diagnosis of tendinosis or tear.

Posterior acoustic shadowing is present when a hyperechoic structure reflects the ultrasound beam so much that it creates a dark shadow underneath it.^12,14 This phenomenon is possible since the ultrasound beam cannot penetrate the hyperechoic structure and reflects off its inferior tissues. Reverberation is when the beam is repeated back and forth between 2 parallel highly reflective surfaces. The initial reflection will be displayed correctly, while the subsequent ultrasound waves will be delayed and appear at a farther distance from the transducer.^12,14

The point where the beam is at its narrowest point generates the section of the image that is best visualized.¹⁵ This is called the focal zone, and it can be adjusted to highlight the desired area of evaluation. Gain controls adjust the amount of black, gray, and white on the monitor and can be adjusted to focus the desired image.¹³ Depth settings are fundamental in finding the desired targets. It is recommended to start with a higher depth setting to get an overview and progressively decrease the depth to key in on the desired anatomy.¹³ Color Doppler can be used to view movement within structures and to identify vessels, synovitis, and neovascularization in tendinopathy.¹³

Ultrasound of the Shoulder

Patients should be seated, if possible, on a rotating seat. The examiner’s shoulder should be higher than the patient’s shoulder.¹⁶ The user holds the ultrasound probe between the thumb and index fingers while resting the hypothenar eminence on the patient to serve as a fulcrum and steadying force. The examination should take 5 to 15 minutes, depending on the examiner’s expertise and the amount of anatomy being scanned.

Examining the body requires knowledge of anatomy. The examination and accuracy are determined by the technician using the probe. The probe can be angled any direction and be placed obliquely on the subject. The advantage here is that anatomy in the human body is not always planar. Muscles and tissues can run obliquely or even perpendicular to each other. When evaluating anatomy, the examiner should keep in mind what structure he or she is looking for; where it should be found; what landmarks can be used to easily locate it; what orientation it has; and what the normal anatomy should look like.

Muscle appears as a lattice with larger areas of hypoechoic muscle tissue and hyperechoic fascial perimysium layers traversing through it.¹⁷ The actual muscle tissue appears hypoechoic from the fluid or blood found within. Scarring, fibrosis, calcification, or chronic injury will change the tissue to appear denser or hyperechoic.¹⁷ Acute injury will appear hypoechoic from the inflammatory response and influx of blood. Tendon appears dense and hyperechoic with striations within the tissue, sometimes referred to as a horse’s tail.¹⁷ When torn, there will be a disassociation of the tissue with a hypoechoic region between the 2 ends. The attachment to the bone and muscle tissue should appear uniform. Hyperechoic areas within the tendon may be from calcification. Ligament appears similar to tendon but is more isoechoic and connects bone to bone. Evaluation of the entire length and the attachments to the bone are critical to evaluate for disease.

Bone appears bright hyperechoic, smooth, and flat, while hyaline cartilage is hypoechoic, smooth, and runs superiorly in a parallel pattern to its respective inferior cortical bone.¹⁷

Fibrocartilage is hyperechoic and typically triangularly shaped, such as in the glenohumeral labrum. Nerves appear fascicular and hypoechoic surrounded by hyperechoic epineurium.¹⁴

The epidermis and dermis are the most superficial structure on top of the screen, and are also hyperechoic.¹⁷

The Diagnostic Shoulder Examination

The proximal long head of the biceps tendon (LHBT) is the easiest structure in the shoulder to identify because of the anatomic structure, the bicipital groove. By keeping the arm relaxed, perpendicular to the ground, and in neutral rotation, the probe can be placed perpendicular to the arm over the proximal shoulder (Figure 1A).^16-20 By finding the groove, the biceps tendon will usually be found resting within the groove (Figure 1B). This is the short axis view and is equivalent to an MRI in the axial plane.

The long axis view of the proximal biceps tendon is found by keeping the tendon in the center of the screen/probe. The probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The user should be sure to visualize the entire tendon on the screen. If only part of the tendon is seen along only part of the screen, then the probe is oblique to the tendon. In this case, the probe area showing the tendon must be stabilized as the center or set point. The other part of the probe will then pivot until all of the tendon is seen on the screen. The MRI equivalent to the long axis of the proximal biceps tendon is the sagittal view.

Ultrasound is a dynamic evaluation. Moving the probe or moving the patient will change what and how something is imaged. The proximal biceps tendon is a good example of this concept. The bicipital groove is very deep proximally and flattens out as it travels distally to the mid-humerus. The examiner should continually adjust his or her hand/probe/patient position as well as depth/gain and other console functions to adapt to the dynamics of the scan. While keeping the bicep tendon in a short axis view, the tendon can be dynamically evaluated for subluxation by internally and externally rotating the arm.

To find the subscapularis, the arm remains in a neutral position with the hand supinated and the probe is held parallel with the ground. After finding the bicipital groove, the subscapularis tendon insertion is just medial to the groove (Figure 1B). By externally rotating the arm, the subscapularis tendon/muscle will come into a long axis view.^16-20 The MRI equivalent to the long axis view of the subscapularis is the axial view. Dynamic testing can be done by internally and externally rotating the arm to evaluate for impingement of the subscapularis tendon as it slides underneath the coracoid process. To view the subscapularis tendon in short axis, the tendon is kept in the center of the screen/probe, and the probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The MRI equivalent is the sagittal view.

Some have recommended using the modified Crass or Middleton position to evaluate the supraspinatus, where the hand is in the “back pocket”.¹⁹ However, many patients with shoulder pain have trouble with this position. By resting the ipsilateral hand on the ipsilateral hip and then dropping the elbow, the supraspinatus insertion can still be brought out from under the acromion. This does bring the insertion anterior out of the scapular plane, so an adjustment is required in probe positioning to properly see the supraspinatus short and long axis. To find the long axis, the probe is placed parallel to a plane that spans the contralateral shoulder and ipsilateral hip (Figure 2A). The fibers of the supraspinatus should be inserting directly lateral to the humeral head without any intervening space (Figure 2B). If any space exists, a partial articular supraspinatus tendon avulsion (PASTA) lesion is present, and its thickness can be directly measured. Moving more posterior will show the flattening of the tuberosity and the fibers of the infraspinatus moving away from the humeral head—the bare spot. The MRI equivalent is the coronal view.

To view the supraspinatus tendon in short axis, maintain the arm in the same position, keeping the tendon in the center of the screen/probe. The probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The probe should now be in a parallel plane between the ipsilateral shoulder and the contralateral hip. The biceps tendon in cross-section will be found anteriorly, and the articular cartilage will appear as a black layer over the bone. Dynamic testing includes placing the probe in a coronal plane between the acromion and greater tuberosity. When the patient abducts the arm while in internal rotation, the supraspinatus tendon will slide underneath the coracoacromial arch showing potential external impingement.¹⁵ The MRI equivalent is the sagittal plane.

The glenohumeral joint is best viewed posteriorly, limiting how much of the intra-articular portion of the joint can be imaged. The arm remains in a neutral position; palpate for the posterior acromion and place the probe just inferior to it, wedging up against it (Figure 3A). The glenohumeral joint will be seen by keeping the probe parallel to the ground (Figure 3B). The MRI equivalent is the axial plane. If a joint effusion exists, it can be seen in the posterior recess.¹⁵ A hyperechoic triangular region in between the humeral head and the glenoid will represent the glenoid labrum (Figure 3B). By internally and externally rotating the arm, the joint and labrum complex can be dynamically examined. From the labrum, scanning superior and medial can sometimes show the spinoglenoid notch where a paralabral cyst might be seen.¹⁵

Using the glenohumeral joint as a reference, the infraspinatus muscle is easily visualized. Maintaining the arm in neutral position with the probe over the glenohumeral joint, the infraspinatus will become apparent as it lays in long axis view superficially between the posterior deltoid and glenohumeral joint (Figure 3B).^16-20 The teres minor lies just inferiorly. The MRI equivalent is the axial plane. To view the infraspinatus and teres minor in short axis, the probe is then rotated 90° on its center axis. The infraspinatus (superiorly) and teres minor (inferiorly) muscles will be visible in short axis within the infraspinatus fossa.¹⁵ The MRI equivalent is the sagittal view.

The acromioclavicular joint is superficial and easy to image. The arm remains in a neutral position, and we can palpate the joint for easy localization. The probe is placed anteriorly in a coronal plane over the acromion and clavicle. By scanning anteriorly and posteriorly, a joint effusion referred to as a Geyser sign might be seen. The MRI equivalent is the coronal view.

Available Certifications

The AIUM certification is a voluntary peer reviewed process that acknowledges that a practice is meeting national standards and aids in improving their respective MSK ultrasound protocols. They also provide guidelines on demonstrating training and competence on performing and/or interpreting diagnostic MSK examinations (Table).¹⁰ The ARDMS certification provides an actual individual certification referred to as “Registered” in MSK ultrasound.¹¹ The physician must perform 150 diagnostic MSK ultrasound evaluations within 36 months of applying and pass a 200-question examination that is offered twice per year.¹¹ None of these certifications are mandated by the American Medical Association (AMA) or American Osteopathic Association (AOA).

Maintenance and Continuing Medical Education (CME)

The AIUM recommends that a minimum of 50 diagnostic MSK ultrasound evaluations be performed per year for skill maintenance.¹⁰ Furthermore, 10 hours of AMA PRA Category 1 Credits™ or American Osteopathic Association Category 1-A Credits specific to MSK ultrasound must be completed by physicians performing and/or interpreting these examinations every 3 years.¹⁰ ARDMS recommends a minimum of 30 MSK ultrasound-specific CMEs in preparation for their “Registered” MSK evaluation.¹

Conclusion

MSK ultrasound is a dynamic, real-time imaging modality that can improve cost efficiency and patient care. Its portability allows for its use anywhere. Learning the skill may seem daunting, but with the proper courses and education, the technology can be easily learned. By correlating a known modality like MRI, the user will easily begin to read ultrasound images. No current certification is needed to use or bill for ultrasound, but various institutions are developing criteria and testing. Two organizations, AIUM and ARDMS, provide guidelines and certifications to demonstrate competency, which may become necessary in the very near future.

The musculoskeletal (MSK) ultrasound evaluation of the shoulder provides a cost- and time-efficient imaging modality with similar diagnostic power as magnetic resonance imaging (MRI).^1,2 Its portable point-of-care applications can be used in the office, in the operating room, and in sideline athletic event coverage, as we discussed in Part 1 of this series.³

MSK ultrasound may seem difficult and daunting, and many articles have quoted steep learning curves.^4,5 However, in our experience in teaching many ultrasound courses, this modality can be learned quite quickly with the proper instruction. Physicians are already familiar with anatomy and usually have had some exposure to MRI.⁴ Taking courses in MSK ultrasound or simply learning the basic concepts of ultrasound and then learning the machine controls is usually a good start.^5-8 Practice scanning normal individuals, comparing the images from an MRI to learn how to reproduce the same planes and images. This will allow the user to become familiar with normal anatomy and how to see the images on the ultrasound screen.^5-8 Vollman and colleagues⁹ showed that in trainees, combining MRI images with sonograms enhances the ability to correctly identify MSK ultrasound anatomy from 40.9% to 72.5%, when compared with learning from ultrasound images alone.

There are currently no certifications necessary to perform ultrasound scans or bill for them; however, some insurance carriers may require demonstrating relevant, documented training for reimbursement.³ Various organizations are trying to develop certifications and regulations for ultrasound to standardize the use of this modality. In the United States, the American Institute of Ultrasound in Medicine (AIUM) and the American Registry for Diagnostic Medical Sonography (ARDMS) provide guidelines and particular MSK ultrasound certifications.^10,11

Basic Ultrasound Principles

The ultrasound machine creates electrical impulses that are turned into sound waves by piezoelectric crystals at the probe’s footprint. These sound waves bounce off tissues and return to the probe, where they are converted electronically to an image on the monitor. Depending on the echogenicity of the scanned tissue, the ultrasound beam will either reflect or be absorbed at different rates. This variance is transmitted on the monitor as a grayscale image. When ultrasound waves are highly reflective, like in bone or fat, they are characterized as hyperechoic. The opposite occurs when ultrasound waves are absorbed like in the fluid of a cystic cavity or joint effusion, and the image appears black. This is described as anechoic.¹² Intermediate tissues such as tendons that are less reflective are seen as hypoechoic and appear gray. When a tissue has a similar echogenicity to its surrounding tissues, it is called isoechoic.¹²

The transducer is the scanning component of the ultrasound machine. Transducers come in 2 shapes: linear and curvilinear. The linear probe creates a straight image that is equal to the size of the transducer footprint. The curvilinear probe creates a wider, wedge-shaped panoramic image.

Linear probes are of higher frequency and generate higher resolution images of shallower structures, while curvilinear probes have greater depth penetration but generate lower resolution images. A high frequency of 10 to 15 MHz is preferred for anatomy between 2 cm to 4 cm depth.¹³ Midrange frequency of 5 to 10 MHz is preferred at 5 cm to 6 cm depth, and low-frequency 2 to 5 MHz probes are preferred for anatomical structures >6 cm depth.¹³

Anisotropy is the property of being directionally dependent, as opposed to isotropy, which implies identical properties in all directions. This anisotropic effect is dependent on the angle of the insonating beam. The maximum return echo occurs when the ultrasound beam is perpendicular to the tendon. Decreasing the insonating angle on a normal tendon will cause it to change from brightly hyperechoic (the actual echo from tightly bound tendon fibers) to darkly hypoechoic. If the angle is then increased, the tendon will again appear hyperechoic. If the artifact causes a normal tendon to appear hypoechoic, it may falsely lead to a diagnosis of tendinosis or tear.

Posterior acoustic shadowing is present when a hyperechoic structure reflects the ultrasound beam so much that it creates a dark shadow underneath it.^12,14 This phenomenon is possible since the ultrasound beam cannot penetrate the hyperechoic structure and reflects off its inferior tissues. Reverberation is when the beam is repeated back and forth between 2 parallel highly reflective surfaces. The initial reflection will be displayed correctly, while the subsequent ultrasound waves will be delayed and appear at a farther distance from the transducer.^12,14

The point where the beam is at its narrowest point generates the section of the image that is best visualized.¹⁵ This is called the focal zone, and it can be adjusted to highlight the desired area of evaluation. Gain controls adjust the amount of black, gray, and white on the monitor and can be adjusted to focus the desired image.¹³ Depth settings are fundamental in finding the desired targets. It is recommended to start with a higher depth setting to get an overview and progressively decrease the depth to key in on the desired anatomy.¹³ Color Doppler can be used to view movement within structures and to identify vessels, synovitis, and neovascularization in tendinopathy.¹³

Ultrasound of the Shoulder

Patients should be seated, if possible, on a rotating seat. The examiner’s shoulder should be higher than the patient’s shoulder.¹⁶ The user holds the ultrasound probe between the thumb and index fingers while resting the hypothenar eminence on the patient to serve as a fulcrum and steadying force. The examination should take 5 to 15 minutes, depending on the examiner’s expertise and the amount of anatomy being scanned.

Examining the body requires knowledge of anatomy. The examination and accuracy are determined by the technician using the probe. The probe can be angled any direction and be placed obliquely on the subject. The advantage here is that anatomy in the human body is not always planar. Muscles and tissues can run obliquely or even perpendicular to each other. When evaluating anatomy, the examiner should keep in mind what structure he or she is looking for; where it should be found; what landmarks can be used to easily locate it; what orientation it has; and what the normal anatomy should look like.

Muscle appears as a lattice with larger areas of hypoechoic muscle tissue and hyperechoic fascial perimysium layers traversing through it.¹⁷ The actual muscle tissue appears hypoechoic from the fluid or blood found within. Scarring, fibrosis, calcification, or chronic injury will change the tissue to appear denser or hyperechoic.¹⁷ Acute injury will appear hypoechoic from the inflammatory response and influx of blood. Tendon appears dense and hyperechoic with striations within the tissue, sometimes referred to as a horse’s tail.¹⁷ When torn, there will be a disassociation of the tissue with a hypoechoic region between the 2 ends. The attachment to the bone and muscle tissue should appear uniform. Hyperechoic areas within the tendon may be from calcification. Ligament appears similar to tendon but is more isoechoic and connects bone to bone. Evaluation of the entire length and the attachments to the bone are critical to evaluate for disease.

Bone appears bright hyperechoic, smooth, and flat, while hyaline cartilage is hypoechoic, smooth, and runs superiorly in a parallel pattern to its respective inferior cortical bone.¹⁷

Fibrocartilage is hyperechoic and typically triangularly shaped, such as in the glenohumeral labrum. Nerves appear fascicular and hypoechoic surrounded by hyperechoic epineurium.¹⁴

The epidermis and dermis are the most superficial structure on top of the screen, and are also hyperechoic.¹⁷

The Diagnostic Shoulder Examination

The proximal long head of the biceps tendon (LHBT) is the easiest structure in the shoulder to identify because of the anatomic structure, the bicipital groove. By keeping the arm relaxed, perpendicular to the ground, and in neutral rotation, the probe can be placed perpendicular to the arm over the proximal shoulder (Figure 1A).^16-20 By finding the groove, the biceps tendon will usually be found resting within the groove (Figure 1B). This is the short axis view and is equivalent to an MRI in the axial plane.

The long axis view of the proximal biceps tendon is found by keeping the tendon in the center of the screen/probe. The probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The user should be sure to visualize the entire tendon on the screen. If only part of the tendon is seen along only part of the screen, then the probe is oblique to the tendon. In this case, the probe area showing the tendon must be stabilized as the center or set point. The other part of the probe will then pivot until all of the tendon is seen on the screen. The MRI equivalent to the long axis of the proximal biceps tendon is the sagittal view.

Ultrasound is a dynamic evaluation. Moving the probe or moving the patient will change what and how something is imaged. The proximal biceps tendon is a good example of this concept. The bicipital groove is very deep proximally and flattens out as it travels distally to the mid-humerus. The examiner should continually adjust his or her hand/probe/patient position as well as depth/gain and other console functions to adapt to the dynamics of the scan. While keeping the bicep tendon in a short axis view, the tendon can be dynamically evaluated for subluxation by internally and externally rotating the arm.

To find the subscapularis, the arm remains in a neutral position with the hand supinated and the probe is held parallel with the ground. After finding the bicipital groove, the subscapularis tendon insertion is just medial to the groove (Figure 1B). By externally rotating the arm, the subscapularis tendon/muscle will come into a long axis view.^16-20 The MRI equivalent to the long axis view of the subscapularis is the axial view. Dynamic testing can be done by internally and externally rotating the arm to evaluate for impingement of the subscapularis tendon as it slides underneath the coracoid process. To view the subscapularis tendon in short axis, the tendon is kept in the center of the screen/probe, and the probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The MRI equivalent is the sagittal view.

Some have recommended using the modified Crass or Middleton position to evaluate the supraspinatus, where the hand is in the “back pocket”.¹⁹ However, many patients with shoulder pain have trouble with this position. By resting the ipsilateral hand on the ipsilateral hip and then dropping the elbow, the supraspinatus insertion can still be brought out from under the acromion. This does bring the insertion anterior out of the scapular plane, so an adjustment is required in probe positioning to properly see the supraspinatus short and long axis. To find the long axis, the probe is placed parallel to a plane that spans the contralateral shoulder and ipsilateral hip (Figure 2A). The fibers of the supraspinatus should be inserting directly lateral to the humeral head without any intervening space (Figure 2B). If any space exists, a partial articular supraspinatus tendon avulsion (PASTA) lesion is present, and its thickness can be directly measured. Moving more posterior will show the flattening of the tuberosity and the fibers of the infraspinatus moving away from the humeral head—the bare spot. The MRI equivalent is the coronal view.

To view the supraspinatus tendon in short axis, maintain the arm in the same position, keeping the tendon in the center of the screen/probe. The probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The probe should now be in a parallel plane between the ipsilateral shoulder and the contralateral hip. The biceps tendon in cross-section will be found anteriorly, and the articular cartilage will appear as a black layer over the bone. Dynamic testing includes placing the probe in a coronal plane between the acromion and greater tuberosity. When the patient abducts the arm while in internal rotation, the supraspinatus tendon will slide underneath the coracoacromial arch showing potential external impingement.¹⁵ The MRI equivalent is the sagittal plane.

The glenohumeral joint is best viewed posteriorly, limiting how much of the intra-articular portion of the joint can be imaged. The arm remains in a neutral position; palpate for the posterior acromion and place the probe just inferior to it, wedging up against it (Figure 3A). The glenohumeral joint will be seen by keeping the probe parallel to the ground (Figure 3B). The MRI equivalent is the axial plane. If a joint effusion exists, it can be seen in the posterior recess.¹⁵ A hyperechoic triangular region in between the humeral head and the glenoid will represent the glenoid labrum (Figure 3B). By internally and externally rotating the arm, the joint and labrum complex can be dynamically examined. From the labrum, scanning superior and medial can sometimes show the spinoglenoid notch where a paralabral cyst might be seen.¹⁵

Using the glenohumeral joint as a reference, the infraspinatus muscle is easily visualized. Maintaining the arm in neutral position with the probe over the glenohumeral joint, the infraspinatus will become apparent as it lays in long axis view superficially between the posterior deltoid and glenohumeral joint (Figure 3B).^16-20 The teres minor lies just inferiorly. The MRI equivalent is the axial plane. To view the infraspinatus and teres minor in short axis, the probe is then rotated 90° on its center axis. The infraspinatus (superiorly) and teres minor (inferiorly) muscles will be visible in short axis within the infraspinatus fossa.¹⁵ The MRI equivalent is the sagittal view.

The acromioclavicular joint is superficial and easy to image. The arm remains in a neutral position, and we can palpate the joint for easy localization. The probe is placed anteriorly in a coronal plane over the acromion and clavicle. By scanning anteriorly and posteriorly, a joint effusion referred to as a Geyser sign might be seen. The MRI equivalent is the coronal view.

Available Certifications

The AIUM certification is a voluntary peer reviewed process that acknowledges that a practice is meeting national standards and aids in improving their respective MSK ultrasound protocols. They also provide guidelines on demonstrating training and competence on performing and/or interpreting diagnostic MSK examinations (Table).¹⁰ The ARDMS certification provides an actual individual certification referred to as “Registered” in MSK ultrasound.¹¹ The physician must perform 150 diagnostic MSK ultrasound evaluations within 36 months of applying and pass a 200-question examination that is offered twice per year.¹¹ None of these certifications are mandated by the American Medical Association (AMA) or American Osteopathic Association (AOA).

Maintenance and Continuing Medical Education (CME)

The AIUM recommends that a minimum of 50 diagnostic MSK ultrasound evaluations be performed per year for skill maintenance.¹⁰ Furthermore, 10 hours of AMA PRA Category 1 Credits™ or American Osteopathic Association Category 1-A Credits specific to MSK ultrasound must be completed by physicians performing and/or interpreting these examinations every 3 years.¹⁰ ARDMS recommends a minimum of 30 MSK ultrasound-specific CMEs in preparation for their “Registered” MSK evaluation.¹

Conclusion

MSK ultrasound is a dynamic, real-time imaging modality that can improve cost efficiency and patient care. Its portability allows for its use anywhere. Learning the skill may seem daunting, but with the proper courses and education, the technology can be easily learned. By correlating a known modality like MRI, the user will easily begin to read ultrasound images. No current certification is needed to use or bill for ultrasound, but various institutions are developing criteria and testing. Two organizations, AIUM and ARDMS, provide guidelines and certifications to demonstrate competency, which may become necessary in the very near future.

The musculoskeletal (MSK) ultrasound evaluation of the shoulder provides a cost- and time-efficient imaging modality with similar diagnostic power as magnetic resonance imaging (MRI).^1,2 Its portable point-of-care applications can be used in the office, in the operating room, and in sideline athletic event coverage, as we discussed in Part 1 of this series.³

MSK ultrasound may seem difficult and daunting, and many articles have quoted steep learning curves.^4,5 However, in our experience in teaching many ultrasound courses, this modality can be learned quite quickly with the proper instruction. Physicians are already familiar with anatomy and usually have had some exposure to MRI.⁴ Taking courses in MSK ultrasound or simply learning the basic concepts of ultrasound and then learning the machine controls is usually a good start.^5-8 Practice scanning normal individuals, comparing the images from an MRI to learn how to reproduce the same planes and images. This will allow the user to become familiar with normal anatomy and how to see the images on the ultrasound screen.^5-8 Vollman and colleagues⁹ showed that in trainees, combining MRI images with sonograms enhances the ability to correctly identify MSK ultrasound anatomy from 40.9% to 72.5%, when compared with learning from ultrasound images alone.

There are currently no certifications necessary to perform ultrasound scans or bill for them; however, some insurance carriers may require demonstrating relevant, documented training for reimbursement.³ Various organizations are trying to develop certifications and regulations for ultrasound to standardize the use of this modality. In the United States, the American Institute of Ultrasound in Medicine (AIUM) and the American Registry for Diagnostic Medical Sonography (ARDMS) provide guidelines and particular MSK ultrasound certifications.^10,11

Basic Ultrasound Principles

The ultrasound machine creates electrical impulses that are turned into sound waves by piezoelectric crystals at the probe’s footprint. These sound waves bounce off tissues and return to the probe, where they are converted electronically to an image on the monitor. Depending on the echogenicity of the scanned tissue, the ultrasound beam will either reflect or be absorbed at different rates. This variance is transmitted on the monitor as a grayscale image. When ultrasound waves are highly reflective, like in bone or fat, they are characterized as hyperechoic. The opposite occurs when ultrasound waves are absorbed like in the fluid of a cystic cavity or joint effusion, and the image appears black. This is described as anechoic.¹² Intermediate tissues such as tendons that are less reflective are seen as hypoechoic and appear gray. When a tissue has a similar echogenicity to its surrounding tissues, it is called isoechoic.¹²

The transducer is the scanning component of the ultrasound machine. Transducers come in 2 shapes: linear and curvilinear. The linear probe creates a straight image that is equal to the size of the transducer footprint. The curvilinear probe creates a wider, wedge-shaped panoramic image.

Linear probes are of higher frequency and generate higher resolution images of shallower structures, while curvilinear probes have greater depth penetration but generate lower resolution images. A high frequency of 10 to 15 MHz is preferred for anatomy between 2 cm to 4 cm depth.¹³ Midrange frequency of 5 to 10 MHz is preferred at 5 cm to 6 cm depth, and low-frequency 2 to 5 MHz probes are preferred for anatomical structures >6 cm depth.¹³

Anisotropy is the property of being directionally dependent, as opposed to isotropy, which implies identical properties in all directions. This anisotropic effect is dependent on the angle of the insonating beam. The maximum return echo occurs when the ultrasound beam is perpendicular to the tendon. Decreasing the insonating angle on a normal tendon will cause it to change from brightly hyperechoic (the actual echo from tightly bound tendon fibers) to darkly hypoechoic. If the angle is then increased, the tendon will again appear hyperechoic. If the artifact causes a normal tendon to appear hypoechoic, it may falsely lead to a diagnosis of tendinosis or tear.

Posterior acoustic shadowing is present when a hyperechoic structure reflects the ultrasound beam so much that it creates a dark shadow underneath it.^12,14 This phenomenon is possible since the ultrasound beam cannot penetrate the hyperechoic structure and reflects off its inferior tissues. Reverberation is when the beam is repeated back and forth between 2 parallel highly reflective surfaces. The initial reflection will be displayed correctly, while the subsequent ultrasound waves will be delayed and appear at a farther distance from the transducer.^12,14

The point where the beam is at its narrowest point generates the section of the image that is best visualized.¹⁵ This is called the focal zone, and it can be adjusted to highlight the desired area of evaluation. Gain controls adjust the amount of black, gray, and white on the monitor and can be adjusted to focus the desired image.¹³ Depth settings are fundamental in finding the desired targets. It is recommended to start with a higher depth setting to get an overview and progressively decrease the depth to key in on the desired anatomy.¹³ Color Doppler can be used to view movement within structures and to identify vessels, synovitis, and neovascularization in tendinopathy.¹³

Ultrasound of the Shoulder

Patients should be seated, if possible, on a rotating seat. The examiner’s shoulder should be higher than the patient’s shoulder.¹⁶ The user holds the ultrasound probe between the thumb and index fingers while resting the hypothenar eminence on the patient to serve as a fulcrum and steadying force. The examination should take 5 to 15 minutes, depending on the examiner’s expertise and the amount of anatomy being scanned.

Examining the body requires knowledge of anatomy. The examination and accuracy are determined by the technician using the probe. The probe can be angled any direction and be placed obliquely on the subject. The advantage here is that anatomy in the human body is not always planar. Muscles and tissues can run obliquely or even perpendicular to each other. When evaluating anatomy, the examiner should keep in mind what structure he or she is looking for; where it should be found; what landmarks can be used to easily locate it; what orientation it has; and what the normal anatomy should look like.

Muscle appears as a lattice with larger areas of hypoechoic muscle tissue and hyperechoic fascial perimysium layers traversing through it.¹⁷ The actual muscle tissue appears hypoechoic from the fluid or blood found within. Scarring, fibrosis, calcification, or chronic injury will change the tissue to appear denser or hyperechoic.¹⁷ Acute injury will appear hypoechoic from the inflammatory response and influx of blood. Tendon appears dense and hyperechoic with striations within the tissue, sometimes referred to as a horse’s tail.¹⁷ When torn, there will be a disassociation of the tissue with a hypoechoic region between the 2 ends. The attachment to the bone and muscle tissue should appear uniform. Hyperechoic areas within the tendon may be from calcification. Ligament appears similar to tendon but is more isoechoic and connects bone to bone. Evaluation of the entire length and the attachments to the bone are critical to evaluate for disease.

Bone appears bright hyperechoic, smooth, and flat, while hyaline cartilage is hypoechoic, smooth, and runs superiorly in a parallel pattern to its respective inferior cortical bone.¹⁷

Fibrocartilage is hyperechoic and typically triangularly shaped, such as in the glenohumeral labrum. Nerves appear fascicular and hypoechoic surrounded by hyperechoic epineurium.¹⁴

The epidermis and dermis are the most superficial structure on top of the screen, and are also hyperechoic.¹⁷

The Diagnostic Shoulder Examination

The proximal long head of the biceps tendon (LHBT) is the easiest structure in the shoulder to identify because of the anatomic structure, the bicipital groove. By keeping the arm relaxed, perpendicular to the ground, and in neutral rotation, the probe can be placed perpendicular to the arm over the proximal shoulder (Figure 1A).^16-20 By finding the groove, the biceps tendon will usually be found resting within the groove (Figure 1B). This is the short axis view and is equivalent to an MRI in the axial plane.

The long axis view of the proximal biceps tendon is found by keeping the tendon in the center of the screen/probe. The probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The user should be sure to visualize the entire tendon on the screen. If only part of the tendon is seen along only part of the screen, then the probe is oblique to the tendon. In this case, the probe area showing the tendon must be stabilized as the center or set point. The other part of the probe will then pivot until all of the tendon is seen on the screen. The MRI equivalent to the long axis of the proximal biceps tendon is the sagittal view.

Ultrasound is a dynamic evaluation. Moving the probe or moving the patient will change what and how something is imaged. The proximal biceps tendon is a good example of this concept. The bicipital groove is very deep proximally and flattens out as it travels distally to the mid-humerus. The examiner should continually adjust his or her hand/probe/patient position as well as depth/gain and other console functions to adapt to the dynamics of the scan. While keeping the bicep tendon in a short axis view, the tendon can be dynamically evaluated for subluxation by internally and externally rotating the arm.

To find the subscapularis, the arm remains in a neutral position with the hand supinated and the probe is held parallel with the ground. After finding the bicipital groove, the subscapularis tendon insertion is just medial to the groove (Figure 1B). By externally rotating the arm, the subscapularis tendon/muscle will come into a long axis view.^16-20 The MRI equivalent to the long axis view of the subscapularis is the axial view. Dynamic testing can be done by internally and externally rotating the arm to evaluate for impingement of the subscapularis tendon as it slides underneath the coracoid process. To view the subscapularis tendon in short axis, the tendon is kept in the center of the screen/probe, and the probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The MRI equivalent is the sagittal view.

Some have recommended using the modified Crass or Middleton position to evaluate the supraspinatus, where the hand is in the “back pocket”.¹⁹ However, many patients with shoulder pain have trouble with this position. By resting the ipsilateral hand on the ipsilateral hip and then dropping the elbow, the supraspinatus insertion can still be brought out from under the acromion. This does bring the insertion anterior out of the scapular plane, so an adjustment is required in probe positioning to properly see the supraspinatus short and long axis. To find the long axis, the probe is placed parallel to a plane that spans the contralateral shoulder and ipsilateral hip (Figure 2A). The fibers of the supraspinatus should be inserting directly lateral to the humeral head without any intervening space (Figure 2B). If any space exists, a partial articular supraspinatus tendon avulsion (PASTA) lesion is present, and its thickness can be directly measured. Moving more posterior will show the flattening of the tuberosity and the fibers of the infraspinatus moving away from the humeral head—the bare spot. The MRI equivalent is the coronal view.

To view the supraspinatus tendon in short axis, maintain the arm in the same position, keeping the tendon in the center of the screen/probe. The probe is then rotated 90° on its center axis, keeping the tendon centered on the probe. The probe should now be in a parallel plane between the ipsilateral shoulder and the contralateral hip. The biceps tendon in cross-section will be found anteriorly, and the articular cartilage will appear as a black layer over the bone. Dynamic testing includes placing the probe in a coronal plane between the acromion and greater tuberosity. When the patient abducts the arm while in internal rotation, the supraspinatus tendon will slide underneath the coracoacromial arch showing potential external impingement.¹⁵ The MRI equivalent is the sagittal plane.

The glenohumeral joint is best viewed posteriorly, limiting how much of the intra-articular portion of the joint can be imaged. The arm remains in a neutral position; palpate for the posterior acromion and place the probe just inferior to it, wedging up against it (Figure 3A). The glenohumeral joint will be seen by keeping the probe parallel to the ground (Figure 3B). The MRI equivalent is the axial plane. If a joint effusion exists, it can be seen in the posterior recess.¹⁵ A hyperechoic triangular region in between the humeral head and the glenoid will represent the glenoid labrum (Figure 3B). By internally and externally rotating the arm, the joint and labrum complex can be dynamically examined. From the labrum, scanning superior and medial can sometimes show the spinoglenoid notch where a paralabral cyst might be seen.¹⁵

Using the glenohumeral joint as a reference, the infraspinatus muscle is easily visualized. Maintaining the arm in neutral position with the probe over the glenohumeral joint, the infraspinatus will become apparent as it lays in long axis view superficially between the posterior deltoid and glenohumeral joint (Figure 3B).^16-20 The teres minor lies just inferiorly. The MRI equivalent is the axial plane. To view the infraspinatus and teres minor in short axis, the probe is then rotated 90° on its center axis. The infraspinatus (superiorly) and teres minor (inferiorly) muscles will be visible in short axis within the infraspinatus fossa.¹⁵ The MRI equivalent is the sagittal view.

The acromioclavicular joint is superficial and easy to image. The arm remains in a neutral position, and we can palpate the joint for easy localization. The probe is placed anteriorly in a coronal plane over the acromion and clavicle. By scanning anteriorly and posteriorly, a joint effusion referred to as a Geyser sign might be seen. The MRI equivalent is the coronal view.

Available Certifications

The AIUM certification is a voluntary peer reviewed process that acknowledges that a practice is meeting national standards and aids in improving their respective MSK ultrasound protocols. They also provide guidelines on demonstrating training and competence on performing and/or interpreting diagnostic MSK examinations (Table).¹⁰ The ARDMS certification provides an actual individual certification referred to as “Registered” in MSK ultrasound.¹¹ The physician must perform 150 diagnostic MSK ultrasound evaluations within 36 months of applying and pass a 200-question examination that is offered twice per year.¹¹ None of these certifications are mandated by the American Medical Association (AMA) or American Osteopathic Association (AOA).

Maintenance and Continuing Medical Education (CME)

The AIUM recommends that a minimum of 50 diagnostic MSK ultrasound evaluations be performed per year for skill maintenance.¹⁰ Furthermore, 10 hours of AMA PRA Category 1 Credits™ or American Osteopathic Association Category 1-A Credits specific to MSK ultrasound must be completed by physicians performing and/or interpreting these examinations every 3 years.¹⁰ ARDMS recommends a minimum of 30 MSK ultrasound-specific CMEs in preparation for their “Registered” MSK evaluation.¹

Conclusion

MSK ultrasound is a dynamic, real-time imaging modality that can improve cost efficiency and patient care. Its portability allows for its use anywhere. Learning the skill may seem daunting, but with the proper courses and education, the technology can be easily learned. By correlating a known modality like MRI, the user will easily begin to read ultrasound images. No current certification is needed to use or bill for ultrasound, but various institutions are developing criteria and testing. Two organizations, AIUM and ARDMS, provide guidelines and certifications to demonstrate competency, which may become necessary in the very near future.

Total shoulder arthroplasty (TSA) has demonstrated excellent long-term clinical outcomes for the treatment of advanced glenohumeral osteoarthritis (OA).^1-5 Glenohumeral OA is characterized by a broad spectrum of glenoid pathology. Both the morphology of the glenoid and humeral head subluxation are important preoperative factors to evaluate, as these have been shown to adversely impact shoulder arthroplasty outcomes.^6,7

Walch and colleagues⁸ have previously classified glenoid morphology in cases of advanced glenohumeral arthritis based on the preoperative computed tomography (CT) scans of individuals undergoing shoulder arthroplasty (Figures 1A-1E). The biconcave (B2) glenoid is characterized by asymmetric posterior bone loss and a posterior translated humeral head that is seated in a biconcave glenoid. The degree and extent of bone loss in the B2 glenoid can be highly variable, ranging from the classic interpretation, in which 50% of the native glenoid fossa is preserved, to the more extreme case with little remaining native anterior glenoid. Scalise and colleagues⁹ have reported that determining the premorbid native glenoid version with a 3-dimensional (3D) glenoid vault model can aid in differentiating a pathologic B2 glenoid from a nonpathologic type C glenoid.

The B2 glenoid in particular has been associated with poor shoulder arthroplasty outcomes and component survivorship.^6,10-12 There are many factors that are thought to contribute to this problem, such as glenoid component malposition, or undercorrection of the pathologic retroversion.^6,13,14 Walch and colleagues¹⁰ reported that if the neoglenoid retroversion was greater than 27°, there was a 44% incidence of loosening and/or instability and 60% of the dislocations were observed when the humeral head subluxation was greater than 80%. Cases with severe posterior glenoid bone deficiency present a unique challenge to the surgeon, and the ability to accurately and securely place an implant in the correct anatomic position can be compromised. Standard TSA has proven excellent outcomes in the setting of typical glenohumeral OA, but in the B2 glenoid with significant posterior bone erosion, additional attention must be given to ensure adequate correction of the bony deformity, soft tissue balancing, and implant stability.

Several strategies that have been proposed to address extreme bone loss in the B2 glenoid will be discussed in this review. These include hemiarthroplasty, TSA with asymmetric reaming of the high side, TSA with bone grafting of the posterior glenoid bone loss, TSA with an augmented glenoid component, and reverse shoulder arthroplasty (RSA). Importantly, while these techniques have been proposed for managing the B2 glenoid, currently there is no gold standard consensus for the treatment of this condition. The purpose of this review is to highlight important characteristics of the B2 glenoid morphology on clinical outcomes and discuss the current surgical management options for this condition.

Preoperative Planning

Being able to accurately determine the amount of retroversion is critical for preoperative planning. Friedman and colleagues¹⁵ initially described a method to measure glenoid retroversion; however, this is less accurate in B2 glenoids (Figures 2A, 2B). More recently, Rouleau and colleagues¹⁶ have validated and published methods to measure glenoid retroversion and subluxation in the B2 glenoid using 3 reference lines: the paleoglenoid (native glenoid surface), intermediate glenoid (line from anterior and posterior edge), and neoglenoid (eroded posterior surface) (Figure 2).

Preoperative evaluation starts with plain radiographs; however, additional imaging is needed, as the axillary view has shown to overestimate retroversion in 86% of patients (Figures 3A-3E).¹⁷ For a detailed evaluation of the glenoid retroversion and bone deficiency, CT scans with 3D reconstructions are useful.^18,19 The surgical plan should be guided by the location and extent of glenoid bone loss. One tool that has been developed to help in predicting premorbid glenoid version, inclination, and position of the joint line is the 3D virtual glenoid vault model.^9,20,21 This helps determine accurate premorbid glenoid anatomy and has been shown to assist in the selection of the optimal implant in an attempt to restore native glenoid anatomy, and avoid peg perforation.²¹ Patient-specific instrumentation (PSI) for shoulder arthroplasty is being used more frequently and has shown promise for more accurate glenoid component placement, particularly in the complex glenoid with severe bone deficiency. PSI involves creating a custom-fitted guide that is referenced to surface anatomy derived from the preoperative CT scan, which can then direct the surgeon toward optimal implant position with regard to glenoid component location, version and inclination (Figures 4A, 4B). Early reports show that PSI has resulted in a significant reduction in the frequency of malpositioned glenoid implants, with the greatest benefit observed in patients with retroversion in excess of 16°.²²

Surgical Management

Hemiarthroplasty

Shoulder hemiarthroplasty has been traditionally described as an option for younger, more active patients in whom longevity of the glenoid component is a concern, or in patients with inadequate glenoid bone stock to tolerate a glenoid component. While there are no reports of hemiarthroplasty specifically for patients with B2 glenoids, one study has examined the effect of glenoid morphology on the outcomes of hemiarthroplasty for shoulder osteoarthritis. Levine and colleagues⁷ reported inferior clinical outcomes after shoulder hemiarthroplasty in patients with eccentric posterior glenoid wear. Several authors have advocated a “ream-and-run” technique to create a concentric glenoid and re-center the humeral head while still maintaining the native glenoid.^23,24 However, in a recent series of 162 ream-and-run procedures, Gilmer and colleagues²⁵ reported that only 23% of patients with B2 glenoid geometry achieved a minimal clinically important change in patient-reported outcome scores and 14% required revision. Furthermore, Lynch and colleagues²⁶ found that progressive medial erosion and recurrent posterior glenoid erosion occur in a significant percentage of patients at early follow-up. Given these recent findings, the use of hemiarthroplasty alone or a ream-and-run procedure for patients with B2 glenoid morphology should be approached with caution.

Total Shoulder Arthroplasty

As with any TSA, the primary goals in treating patients with B2 glenoid defects are to provide the patient with a pain-free, stable, and functional shoulder (Figures 5A-5D). There are, however, a few challenges that are unique to TSA in the setting of B2 glenoid defects. Because the humeral head is often subluxated posteriorly into the defect, the anterior capsule and rotator cuff can tighten while the posterior aspect of the joint becomes lax. These soft tissues must be balanced during TSA in order to stabilize the shoulder and restore the appropriate length-tension relationship of the rotator cuff. The other primary concern is restoration of appropriate glenoid version and lateralization. To accomplish this, the most common techniques utilized are asymmetric reaming, bone graft augmentation, and glenoid component augmentation.^27,28

Asymmetric Reaming. One of the more readily utilized techniques for addressing the B2 glenoid during TSA is eccentric or asymmetric reaming. During this process, the anterior glenoid is preferentially reamed while little to no bone is removed posteriorly. This technique is generally felt to be sufficient to treat posterior defects up to 5 mm to 8 mm or retroversion up to 15°.²⁸ These upper limits have been confirmed in a number of cadaveric and simulated models.^29-31

The success of this technique hinges on excellent glenoid exposure. With appropriate retractors in place, the anterior capsulolabral complex, including the biceps insertion, is resected to improve visualization. The inferior capsule must be resected carefully to ensure exposure and better motion postoperatively. On the other hand, it is imperative to protect the posterior capsulolabral attachments because of the increased risk of posterior instability in patients with B2 glenoids.

Detailed imaging such as CT scans with 3D reconstructions have improved our understanding of the degree of the deformities in all directions, which can better guide the reaming. PSI and planning software developed to improve the surgeon’s ability to place the glenoid component centrally in the best possible position after version correction can be even more helpful. We find that using a burr to provisionally lower the high side (anterior) provides a more en face view, which subsequently makes the eccentric reaming easier. As a guide, we will not ream more than 1 cm of anterior bone or attempt to correct more than ~20° of retroversion. The goal should be to create a glenoid surface that is more neutral and congruent to the posterior surface of the glenoid component while not overmedializing the component.

Although eccentric reaming may be one of the more straightforward methods for addressing posterior glenoid erosion, it is not without a number of potential downsides. When attempting to correct defects >10 mm or retroversion beyond 15°, excessive medialization of the implant can occur. Although increasing the thickness of the glenoid component can compensate for small amounts of medialization, excessive medialization can lead to a number of issues.^27,28,32 As reaming progresses medially, the risk of keel penetration increases as the glenoid vault narrows.^30,32 Further medialization decreases posterior cortical support for the implant, which increases the risk of component loosening and subsidence.^33-35 The more medial the implant is placed, the smaller the surface of available bone for implant fixation. This often requires utilization of a smaller sized glenoid component that may result in component mismatch with the humeral implant. Finally, excessive medialization has the potential to under tension the rotator cuff, leading to decreased shoulder stability, strength, and function.

Bone Graft Augmentation. When posterior erosion becomes too excessive to address with eccentric reaming alone, defect augmentation is another option to consider (Figures 6A-6E). While technically more demanding, bone graft also provides the advantage of better re-creating the natural joint line and center of rotation of the glenohumeral joint.

For most defects, the resected humeral head provides the ideal source of graft. After initial reaming of the anterior glenoid, the defect must be sized and measured. We then recommend using a guided, cannulated system to place a central pin, lying perpendicular to the glenoid axis in neutral position. The anterior glenoid is then reamed enough to create a flat surface on which to attach the bone graft. The posterior surface is then gently burred to create a bleeding surface to enhance graft incorporation. The graft is then contoured to the defect and placed flush with the anterior glenoid. Cannulated screws are placed over guidewires to fix the graft. Using an arthroscopic cannula inserted posteriorly allows for easier placement of the guidewires and easier implantation of the screws. Although a reamer or burr can be used to contour the graft once it is fixed in place, this should be minimized to prevent loss of fixation. When the graft is fixed, we then cement the glenoid component into place.

Although good clinical results have been obtained with this technique, there is concern of incomplete graft healing and component loosening in the long term. Even in clinically asymptomatic and well functioning patients, some degree of radiographic lucency may be present in over 50% of cases.^31,36,37 Glenoid Component Augmentation. To address the issues related to lucency and nonunion of bone graft augmentation, several augmented glenoid components have been developed. Augmented glenoid components have the benefit of filling posterior defects and stabilizing the shoulder without requiring excessive medialization (as often occurs with eccentric reaming) or union of a bone-to-bone interface (as is required in bone graft augmentation).³⁸ Although many of the metal back designs experienced undesirably high failure rates and have since been recalled,³⁹ more modern all-polyethylene components hold promise. The 2 most commonly utilized designs are the posterior step augment (DePuy) and the posterior wedge (Exactech). Although biomechanical analyses of both designs have demonstrated increased stability during loading in cadaveric and simulation models, the step augment (DePuy) has demonstrated increased stability and resistance to loosening.^40,41 Although midterm results are not yet available for this newest generation of augmented components, short-term results with 2 to 3 years of follow-up have demonstrated excellent clinical outcomes.²⁸

Reverse Total Shoulder Arthroplasty

While most commonly indicated for patients with rotator cuff tear arthropathy, RSA has recently been advocated for older patients with osteoarthritis and B2 glenoids in the setting of an intact rotator cuff. The semi-constrained design of the RSA is a potential solution to the static posterior humeral head subluxation seen in patients with B2 glenoid geometry (Figure 6E).

Technically, RSA is often an easier solution than a TSA with bone grafting because there is usually enough glenoid bone stock for fixation. That said, we always get a CT scan with 3D reconstructions to better appreciate the anatomy. Note that in B2 glenoids, the bone loss is typically posterior and inferior. RSA in the setting of a B2 glenoid is one of the ideal indications to use PSI to ensure ideal placement of the central pin, which is the key to glenoid baseplate positioning. Even when using a RSA, eccentric reaming and/or bone grafting allow for more ideal component placement. Using the same eccentric reaming techniques described above, one should try to ream to place the baseplate at 10° of retroversion. In cases where retroversion cannot be corrected to 10°, graft can be taken from the humeral head, iliac crest, or allograft. A benefit to using bone graft with RSA as opposed to TSA is that the graft can be fashioned to the baseplate, impacted/compressed into the B2 glenoid, and then secured with a central compression screw and peripheral locking screws.

Mizuno and colleagues⁴¹ reported a retrospective series of 27 RSAs performed for primary glenohumeral osteoarthritis and biconcave glenoid. At a mean follow-up of nearly 5 years, the authors noted significant improvement in Constant scores and shoulder motion with minimal complications. There was no recurrence of posterior instability observed by the time of final follow-up.⁴¹

RSA is a promising treatment for primary glenohumeral arthritis with posterior glenoid bone loss and static posterior subluxation in elderly or less active patients, but the longevity of these implants has yet to be established for younger, more active patients and requires further study.

Conclusion

Reconstruction of the B2 glenoid presents a challenging clinical problem that has been associated with poor clinical outcomes and implant survivorship. The high failure rate from glenoid component loosening and subsequent premature implant failure can be substantially decreased with accurate glenoid component positioning and appropriate correction of the pathologic glenoid retroversion. Careful preoperative planning is essential for accurate preparation and execution of the optimal surgical plan. There are many surgical strategies to address the B2 glenoid, but no consensus on the optimal method exists, as the technique should be uniquely customized to the individual’s pathology and surgeon preference (Table). Cases with mild deformity may be corrected with eccentric reaming and TSA, while the more severe deformities may require posterior glenoid bone grafting and/or augmented implants to restore native version. Finally, the RSA is a reliable option to restore stability and address bone deficiency for the severe B2 glenoid in an older, lower demand patient.

Total shoulder arthroplasty (TSA) has demonstrated excellent long-term clinical outcomes for the treatment of advanced glenohumeral osteoarthritis (OA).^1-5 Glenohumeral OA is characterized by a broad spectrum of glenoid pathology. Both the morphology of the glenoid and humeral head subluxation are important preoperative factors to evaluate, as these have been shown to adversely impact shoulder arthroplasty outcomes.^6,7

Walch and colleagues⁸ have previously classified glenoid morphology in cases of advanced glenohumeral arthritis based on the preoperative computed tomography (CT) scans of individuals undergoing shoulder arthroplasty (Figures 1A-1E). The biconcave (B2) glenoid is characterized by asymmetric posterior bone loss and a posterior translated humeral head that is seated in a biconcave glenoid. The degree and extent of bone loss in the B2 glenoid can be highly variable, ranging from the classic interpretation, in which 50% of the native glenoid fossa is preserved, to the more extreme case with little remaining native anterior glenoid. Scalise and colleagues⁹ have reported that determining the premorbid native glenoid version with a 3-dimensional (3D) glenoid vault model can aid in differentiating a pathologic B2 glenoid from a nonpathologic type C glenoid.

The B2 glenoid in particular has been associated with poor shoulder arthroplasty outcomes and component survivorship.^6,10-12 There are many factors that are thought to contribute to this problem, such as glenoid component malposition, or undercorrection of the pathologic retroversion.^6,13,14 Walch and colleagues¹⁰ reported that if the neoglenoid retroversion was greater than 27°, there was a 44% incidence of loosening and/or instability and 60% of the dislocations were observed when the humeral head subluxation was greater than 80%. Cases with severe posterior glenoid bone deficiency present a unique challenge to the surgeon, and the ability to accurately and securely place an implant in the correct anatomic position can be compromised. Standard TSA has proven excellent outcomes in the setting of typical glenohumeral OA, but in the B2 glenoid with significant posterior bone erosion, additional attention must be given to ensure adequate correction of the bony deformity, soft tissue balancing, and implant stability.

Several strategies that have been proposed to address extreme bone loss in the B2 glenoid will be discussed in this review. These include hemiarthroplasty, TSA with asymmetric reaming of the high side, TSA with bone grafting of the posterior glenoid bone loss, TSA with an augmented glenoid component, and reverse shoulder arthroplasty (RSA). Importantly, while these techniques have been proposed for managing the B2 glenoid, currently there is no gold standard consensus for the treatment of this condition. The purpose of this review is to highlight important characteristics of the B2 glenoid morphology on clinical outcomes and discuss the current surgical management options for this condition.

Preoperative Planning

Being able to accurately determine the amount of retroversion is critical for preoperative planning. Friedman and colleagues¹⁵ initially described a method to measure glenoid retroversion; however, this is less accurate in B2 glenoids (Figures 2A, 2B). More recently, Rouleau and colleagues¹⁶ have validated and published methods to measure glenoid retroversion and subluxation in the B2 glenoid using 3 reference lines: the paleoglenoid (native glenoid surface), intermediate glenoid (line from anterior and posterior edge), and neoglenoid (eroded posterior surface) (Figure 2).

Preoperative evaluation starts with plain radiographs; however, additional imaging is needed, as the axillary view has shown to overestimate retroversion in 86% of patients (Figures 3A-3E).¹⁷ For a detailed evaluation of the glenoid retroversion and bone deficiency, CT scans with 3D reconstructions are useful.^18,19 The surgical plan should be guided by the location and extent of glenoid bone loss. One tool that has been developed to help in predicting premorbid glenoid version, inclination, and position of the joint line is the 3D virtual glenoid vault model.^9,20,21 This helps determine accurate premorbid glenoid anatomy and has been shown to assist in the selection of the optimal implant in an attempt to restore native glenoid anatomy, and avoid peg perforation.²¹ Patient-specific instrumentation (PSI) for shoulder arthroplasty is being used more frequently and has shown promise for more accurate glenoid component placement, particularly in the complex glenoid with severe bone deficiency. PSI involves creating a custom-fitted guide that is referenced to surface anatomy derived from the preoperative CT scan, which can then direct the surgeon toward optimal implant position with regard to glenoid component location, version and inclination (Figures 4A, 4B). Early reports show that PSI has resulted in a significant reduction in the frequency of malpositioned glenoid implants, with the greatest benefit observed in patients with retroversion in excess of 16°.²²

Surgical Management

Hemiarthroplasty

Shoulder hemiarthroplasty has been traditionally described as an option for younger, more active patients in whom longevity of the glenoid component is a concern, or in patients with inadequate glenoid bone stock to tolerate a glenoid component. While there are no reports of hemiarthroplasty specifically for patients with B2 glenoids, one study has examined the effect of glenoid morphology on the outcomes of hemiarthroplasty for shoulder osteoarthritis. Levine and colleagues⁷ reported inferior clinical outcomes after shoulder hemiarthroplasty in patients with eccentric posterior glenoid wear. Several authors have advocated a “ream-and-run” technique to create a concentric glenoid and re-center the humeral head while still maintaining the native glenoid.^23,24 However, in a recent series of 162 ream-and-run procedures, Gilmer and colleagues²⁵ reported that only 23% of patients with B2 glenoid geometry achieved a minimal clinically important change in patient-reported outcome scores and 14% required revision. Furthermore, Lynch and colleagues²⁶ found that progressive medial erosion and recurrent posterior glenoid erosion occur in a significant percentage of patients at early follow-up. Given these recent findings, the use of hemiarthroplasty alone or a ream-and-run procedure for patients with B2 glenoid morphology should be approached with caution.

Total Shoulder Arthroplasty

As with any TSA, the primary goals in treating patients with B2 glenoid defects are to provide the patient with a pain-free, stable, and functional shoulder (Figures 5A-5D). There are, however, a few challenges that are unique to TSA in the setting of B2 glenoid defects. Because the humeral head is often subluxated posteriorly into the defect, the anterior capsule and rotator cuff can tighten while the posterior aspect of the joint becomes lax. These soft tissues must be balanced during TSA in order to stabilize the shoulder and restore the appropriate length-tension relationship of the rotator cuff. The other primary concern is restoration of appropriate glenoid version and lateralization. To accomplish this, the most common techniques utilized are asymmetric reaming, bone graft augmentation, and glenoid component augmentation.^27,28

Asymmetric Reaming. One of the more readily utilized techniques for addressing the B2 glenoid during TSA is eccentric or asymmetric reaming. During this process, the anterior glenoid is preferentially reamed while little to no bone is removed posteriorly. This technique is generally felt to be sufficient to treat posterior defects up to 5 mm to 8 mm or retroversion up to 15°.²⁸ These upper limits have been confirmed in a number of cadaveric and simulated models.^29-31

The success of this technique hinges on excellent glenoid exposure. With appropriate retractors in place, the anterior capsulolabral complex, including the biceps insertion, is resected to improve visualization. The inferior capsule must be resected carefully to ensure exposure and better motion postoperatively. On the other hand, it is imperative to protect the posterior capsulolabral attachments because of the increased risk of posterior instability in patients with B2 glenoids.

Detailed imaging such as CT scans with 3D reconstructions have improved our understanding of the degree of the deformities in all directions, which can better guide the reaming. PSI and planning software developed to improve the surgeon’s ability to place the glenoid component centrally in the best possible position after version correction can be even more helpful. We find that using a burr to provisionally lower the high side (anterior) provides a more en face view, which subsequently makes the eccentric reaming easier. As a guide, we will not ream more than 1 cm of anterior bone or attempt to correct more than ~20° of retroversion. The goal should be to create a glenoid surface that is more neutral and congruent to the posterior surface of the glenoid component while not overmedializing the component.

Although eccentric reaming may be one of the more straightforward methods for addressing posterior glenoid erosion, it is not without a number of potential downsides. When attempting to correct defects >10 mm or retroversion beyond 15°, excessive medialization of the implant can occur. Although increasing the thickness of the glenoid component can compensate for small amounts of medialization, excessive medialization can lead to a number of issues.^27,28,32 As reaming progresses medially, the risk of keel penetration increases as the glenoid vault narrows.^30,32 Further medialization decreases posterior cortical support for the implant, which increases the risk of component loosening and subsidence.^33-35 The more medial the implant is placed, the smaller the surface of available bone for implant fixation. This often requires utilization of a smaller sized glenoid component that may result in component mismatch with the humeral implant. Finally, excessive medialization has the potential to under tension the rotator cuff, leading to decreased shoulder stability, strength, and function.

Bone Graft Augmentation. When posterior erosion becomes too excessive to address with eccentric reaming alone, defect augmentation is another option to consider (Figures 6A-6E). While technically more demanding, bone graft also provides the advantage of better re-creating the natural joint line and center of rotation of the glenohumeral joint.

For most defects, the resected humeral head provides the ideal source of graft. After initial reaming of the anterior glenoid, the defect must be sized and measured. We then recommend using a guided, cannulated system to place a central pin, lying perpendicular to the glenoid axis in neutral position. The anterior glenoid is then reamed enough to create a flat surface on which to attach the bone graft. The posterior surface is then gently burred to create a bleeding surface to enhance graft incorporation. The graft is then contoured to the defect and placed flush with the anterior glenoid. Cannulated screws are placed over guidewires to fix the graft. Using an arthroscopic cannula inserted posteriorly allows for easier placement of the guidewires and easier implantation of the screws. Although a reamer or burr can be used to contour the graft once it is fixed in place, this should be minimized to prevent loss of fixation. When the graft is fixed, we then cement the glenoid component into place.

Although good clinical results have been obtained with this technique, there is concern of incomplete graft healing and component loosening in the long term. Even in clinically asymptomatic and well functioning patients, some degree of radiographic lucency may be present in over 50% of cases.^31,36,37 Glenoid Component Augmentation. To address the issues related to lucency and nonunion of bone graft augmentation, several augmented glenoid components have been developed. Augmented glenoid components have the benefit of filling posterior defects and stabilizing the shoulder without requiring excessive medialization (as often occurs with eccentric reaming) or union of a bone-to-bone interface (as is required in bone graft augmentation).³⁸ Although many of the metal back designs experienced undesirably high failure rates and have since been recalled,³⁹ more modern all-polyethylene components hold promise. The 2 most commonly utilized designs are the posterior step augment (DePuy) and the posterior wedge (Exactech). Although biomechanical analyses of both designs have demonstrated increased stability during loading in cadaveric and simulation models, the step augment (DePuy) has demonstrated increased stability and resistance to loosening.^40,41 Although midterm results are not yet available for this newest generation of augmented components, short-term results with 2 to 3 years of follow-up have demonstrated excellent clinical outcomes.²⁸

Reverse Total Shoulder Arthroplasty

While most commonly indicated for patients with rotator cuff tear arthropathy, RSA has recently been advocated for older patients with osteoarthritis and B2 glenoids in the setting of an intact rotator cuff. The semi-constrained design of the RSA is a potential solution to the static posterior humeral head subluxation seen in patients with B2 glenoid geometry (Figure 6E).

Technically, RSA is often an easier solution than a TSA with bone grafting because there is usually enough glenoid bone stock for fixation. That said, we always get a CT scan with 3D reconstructions to better appreciate the anatomy. Note that in B2 glenoids, the bone loss is typically posterior and inferior. RSA in the setting of a B2 glenoid is one of the ideal indications to use PSI to ensure ideal placement of the central pin, which is the key to glenoid baseplate positioning. Even when using a RSA, eccentric reaming and/or bone grafting allow for more ideal component placement. Using the same eccentric reaming techniques described above, one should try to ream to place the baseplate at 10° of retroversion. In cases where retroversion cannot be corrected to 10°, graft can be taken from the humeral head, iliac crest, or allograft. A benefit to using bone graft with RSA as opposed to TSA is that the graft can be fashioned to the baseplate, impacted/compressed into the B2 glenoid, and then secured with a central compression screw and peripheral locking screws.

Mizuno and colleagues⁴¹ reported a retrospective series of 27 RSAs performed for primary glenohumeral osteoarthritis and biconcave glenoid. At a mean follow-up of nearly 5 years, the authors noted significant improvement in Constant scores and shoulder motion with minimal complications. There was no recurrence of posterior instability observed by the time of final follow-up.⁴¹

RSA is a promising treatment for primary glenohumeral arthritis with posterior glenoid bone loss and static posterior subluxation in elderly or less active patients, but the longevity of these implants has yet to be established for younger, more active patients and requires further study.

Conclusion

Reconstruction of the B2 glenoid presents a challenging clinical problem that has been associated with poor clinical outcomes and implant survivorship. The high failure rate from glenoid component loosening and subsequent premature implant failure can be substantially decreased with accurate glenoid component positioning and appropriate correction of the pathologic glenoid retroversion. Careful preoperative planning is essential for accurate preparation and execution of the optimal surgical plan. There are many surgical strategies to address the B2 glenoid, but no consensus on the optimal method exists, as the technique should be uniquely customized to the individual’s pathology and surgeon preference (Table). Cases with mild deformity may be corrected with eccentric reaming and TSA, while the more severe deformities may require posterior glenoid bone grafting and/or augmented implants to restore native version. Finally, the RSA is a reliable option to restore stability and address bone deficiency for the severe B2 glenoid in an older, lower demand patient.

Total shoulder arthroplasty (TSA) has demonstrated excellent long-term clinical outcomes for the treatment of advanced glenohumeral osteoarthritis (OA).^1-5 Glenohumeral OA is characterized by a broad spectrum of glenoid pathology. Both the morphology of the glenoid and humeral head subluxation are important preoperative factors to evaluate, as these have been shown to adversely impact shoulder arthroplasty outcomes.^6,7

Walch and colleagues⁸ have previously classified glenoid morphology in cases of advanced glenohumeral arthritis based on the preoperative computed tomography (CT) scans of individuals undergoing shoulder arthroplasty (Figures 1A-1E). The biconcave (B2) glenoid is characterized by asymmetric posterior bone loss and a posterior translated humeral head that is seated in a biconcave glenoid. The degree and extent of bone loss in the B2 glenoid can be highly variable, ranging from the classic interpretation, in which 50% of the native glenoid fossa is preserved, to the more extreme case with little remaining native anterior glenoid. Scalise and colleagues⁹ have reported that determining the premorbid native glenoid version with a 3-dimensional (3D) glenoid vault model can aid in differentiating a pathologic B2 glenoid from a nonpathologic type C glenoid.

The B2 glenoid in particular has been associated with poor shoulder arthroplasty outcomes and component survivorship.^6,10-12 There are many factors that are thought to contribute to this problem, such as glenoid component malposition, or undercorrection of the pathologic retroversion.^6,13,14 Walch and colleagues¹⁰ reported that if the neoglenoid retroversion was greater than 27°, there was a 44% incidence of loosening and/or instability and 60% of the dislocations were observed when the humeral head subluxation was greater than 80%. Cases with severe posterior glenoid bone deficiency present a unique challenge to the surgeon, and the ability to accurately and securely place an implant in the correct anatomic position can be compromised. Standard TSA has proven excellent outcomes in the setting of typical glenohumeral OA, but in the B2 glenoid with significant posterior bone erosion, additional attention must be given to ensure adequate correction of the bony deformity, soft tissue balancing, and implant stability.

Several strategies that have been proposed to address extreme bone loss in the B2 glenoid will be discussed in this review. These include hemiarthroplasty, TSA with asymmetric reaming of the high side, TSA with bone grafting of the posterior glenoid bone loss, TSA with an augmented glenoid component, and reverse shoulder arthroplasty (RSA). Importantly, while these techniques have been proposed for managing the B2 glenoid, currently there is no gold standard consensus for the treatment of this condition. The purpose of this review is to highlight important characteristics of the B2 glenoid morphology on clinical outcomes and discuss the current surgical management options for this condition.

Preoperative Planning

Being able to accurately determine the amount of retroversion is critical for preoperative planning. Friedman and colleagues¹⁵ initially described a method to measure glenoid retroversion; however, this is less accurate in B2 glenoids (Figures 2A, 2B). More recently, Rouleau and colleagues¹⁶ have validated and published methods to measure glenoid retroversion and subluxation in the B2 glenoid using 3 reference lines: the paleoglenoid (native glenoid surface), intermediate glenoid (line from anterior and posterior edge), and neoglenoid (eroded posterior surface) (Figure 2).

Preoperative evaluation starts with plain radiographs; however, additional imaging is needed, as the axillary view has shown to overestimate retroversion in 86% of patients (Figures 3A-3E).¹⁷ For a detailed evaluation of the glenoid retroversion and bone deficiency, CT scans with 3D reconstructions are useful.^18,19 The surgical plan should be guided by the location and extent of glenoid bone loss. One tool that has been developed to help in predicting premorbid glenoid version, inclination, and position of the joint line is the 3D virtual glenoid vault model.^9,20,21 This helps determine accurate premorbid glenoid anatomy and has been shown to assist in the selection of the optimal implant in an attempt to restore native glenoid anatomy, and avoid peg perforation.²¹ Patient-specific instrumentation (PSI) for shoulder arthroplasty is being used more frequently and has shown promise for more accurate glenoid component placement, particularly in the complex glenoid with severe bone deficiency. PSI involves creating a custom-fitted guide that is referenced to surface anatomy derived from the preoperative CT scan, which can then direct the surgeon toward optimal implant position with regard to glenoid component location, version and inclination (Figures 4A, 4B). Early reports show that PSI has resulted in a significant reduction in the frequency of malpositioned glenoid implants, with the greatest benefit observed in patients with retroversion in excess of 16°.²²

Surgical Management

Hemiarthroplasty

Shoulder hemiarthroplasty has been traditionally described as an option for younger, more active patients in whom longevity of the glenoid component is a concern, or in patients with inadequate glenoid bone stock to tolerate a glenoid component. While there are no reports of hemiarthroplasty specifically for patients with B2 glenoids, one study has examined the effect of glenoid morphology on the outcomes of hemiarthroplasty for shoulder osteoarthritis. Levine and colleagues⁷ reported inferior clinical outcomes after shoulder hemiarthroplasty in patients with eccentric posterior glenoid wear. Several authors have advocated a “ream-and-run” technique to create a concentric glenoid and re-center the humeral head while still maintaining the native glenoid.^23,24 However, in a recent series of 162 ream-and-run procedures, Gilmer and colleagues²⁵ reported that only 23% of patients with B2 glenoid geometry achieved a minimal clinically important change in patient-reported outcome scores and 14% required revision. Furthermore, Lynch and colleagues²⁶ found that progressive medial erosion and recurrent posterior glenoid erosion occur in a significant percentage of patients at early follow-up. Given these recent findings, the use of hemiarthroplasty alone or a ream-and-run procedure for patients with B2 glenoid morphology should be approached with caution.

Total Shoulder Arthroplasty

As with any TSA, the primary goals in treating patients with B2 glenoid defects are to provide the patient with a pain-free, stable, and functional shoulder (Figures 5A-5D). There are, however, a few challenges that are unique to TSA in the setting of B2 glenoid defects. Because the humeral head is often subluxated posteriorly into the defect, the anterior capsule and rotator cuff can tighten while the posterior aspect of the joint becomes lax. These soft tissues must be balanced during TSA in order to stabilize the shoulder and restore the appropriate length-tension relationship of the rotator cuff. The other primary concern is restoration of appropriate glenoid version and lateralization. To accomplish this, the most common techniques utilized are asymmetric reaming, bone graft augmentation, and glenoid component augmentation.^27,28

Asymmetric Reaming. One of the more readily utilized techniques for addressing the B2 glenoid during TSA is eccentric or asymmetric reaming. During this process, the anterior glenoid is preferentially reamed while little to no bone is removed posteriorly. This technique is generally felt to be sufficient to treat posterior defects up to 5 mm to 8 mm or retroversion up to 15°.²⁸ These upper limits have been confirmed in a number of cadaveric and simulated models.^29-31

The success of this technique hinges on excellent glenoid exposure. With appropriate retractors in place, the anterior capsulolabral complex, including the biceps insertion, is resected to improve visualization. The inferior capsule must be resected carefully to ensure exposure and better motion postoperatively. On the other hand, it is imperative to protect the posterior capsulolabral attachments because of the increased risk of posterior instability in patients with B2 glenoids.

Detailed imaging such as CT scans with 3D reconstructions have improved our understanding of the degree of the deformities in all directions, which can better guide the reaming. PSI and planning software developed to improve the surgeon’s ability to place the glenoid component centrally in the best possible position after version correction can be even more helpful. We find that using a burr to provisionally lower the high side (anterior) provides a more en face view, which subsequently makes the eccentric reaming easier. As a guide, we will not ream more than 1 cm of anterior bone or attempt to correct more than ~20° of retroversion. The goal should be to create a glenoid surface that is more neutral and congruent to the posterior surface of the glenoid component while not overmedializing the component.

Although eccentric reaming may be one of the more straightforward methods for addressing posterior glenoid erosion, it is not without a number of potential downsides. When attempting to correct defects >10 mm or retroversion beyond 15°, excessive medialization of the implant can occur. Although increasing the thickness of the glenoid component can compensate for small amounts of medialization, excessive medialization can lead to a number of issues.^27,28,32 As reaming progresses medially, the risk of keel penetration increases as the glenoid vault narrows.^30,32 Further medialization decreases posterior cortical support for the implant, which increases the risk of component loosening and subsidence.^33-35 The more medial the implant is placed, the smaller the surface of available bone for implant fixation. This often requires utilization of a smaller sized glenoid component that may result in component mismatch with the humeral implant. Finally, excessive medialization has the potential to under tension the rotator cuff, leading to decreased shoulder stability, strength, and function.

Bone Graft Augmentation. When posterior erosion becomes too excessive to address with eccentric reaming alone, defect augmentation is another option to consider (Figures 6A-6E). While technically more demanding, bone graft also provides the advantage of better re-creating the natural joint line and center of rotation of the glenohumeral joint.

For most defects, the resected humeral head provides the ideal source of graft. After initial reaming of the anterior glenoid, the defect must be sized and measured. We then recommend using a guided, cannulated system to place a central pin, lying perpendicular to the glenoid axis in neutral position. The anterior glenoid is then reamed enough to create a flat surface on which to attach the bone graft. The posterior surface is then gently burred to create a bleeding surface to enhance graft incorporation. The graft is then contoured to the defect and placed flush with the anterior glenoid. Cannulated screws are placed over guidewires to fix the graft. Using an arthroscopic cannula inserted posteriorly allows for easier placement of the guidewires and easier implantation of the screws. Although a reamer or burr can be used to contour the graft once it is fixed in place, this should be minimized to prevent loss of fixation. When the graft is fixed, we then cement the glenoid component into place.

Although good clinical results have been obtained with this technique, there is concern of incomplete graft healing and component loosening in the long term. Even in clinically asymptomatic and well functioning patients, some degree of radiographic lucency may be present in over 50% of cases.^31,36,37 Glenoid Component Augmentation. To address the issues related to lucency and nonunion of bone graft augmentation, several augmented glenoid components have been developed. Augmented glenoid components have the benefit of filling posterior defects and stabilizing the shoulder without requiring excessive medialization (as often occurs with eccentric reaming) or union of a bone-to-bone interface (as is required in bone graft augmentation).³⁸ Although many of the metal back designs experienced undesirably high failure rates and have since been recalled,³⁹ more modern all-polyethylene components hold promise. The 2 most commonly utilized designs are the posterior step augment (DePuy) and the posterior wedge (Exactech). Although biomechanical analyses of both designs have demonstrated increased stability during loading in cadaveric and simulation models, the step augment (DePuy) has demonstrated increased stability and resistance to loosening.^40,41 Although midterm results are not yet available for this newest generation of augmented components, short-term results with 2 to 3 years of follow-up have demonstrated excellent clinical outcomes.²⁸

Reverse Total Shoulder Arthroplasty

While most commonly indicated for patients with rotator cuff tear arthropathy, RSA has recently been advocated for older patients with osteoarthritis and B2 glenoids in the setting of an intact rotator cuff. The semi-constrained design of the RSA is a potential solution to the static posterior humeral head subluxation seen in patients with B2 glenoid geometry (Figure 6E).

Technically, RSA is often an easier solution than a TSA with bone grafting because there is usually enough glenoid bone stock for fixation. That said, we always get a CT scan with 3D reconstructions to better appreciate the anatomy. Note that in B2 glenoids, the bone loss is typically posterior and inferior. RSA in the setting of a B2 glenoid is one of the ideal indications to use PSI to ensure ideal placement of the central pin, which is the key to glenoid baseplate positioning. Even when using a RSA, eccentric reaming and/or bone grafting allow for more ideal component placement. Using the same eccentric reaming techniques described above, one should try to ream to place the baseplate at 10° of retroversion. In cases where retroversion cannot be corrected to 10°, graft can be taken from the humeral head, iliac crest, or allograft. A benefit to using bone graft with RSA as opposed to TSA is that the graft can be fashioned to the baseplate, impacted/compressed into the B2 glenoid, and then secured with a central compression screw and peripheral locking screws.

Mizuno and colleagues⁴¹ reported a retrospective series of 27 RSAs performed for primary glenohumeral osteoarthritis and biconcave glenoid. At a mean follow-up of nearly 5 years, the authors noted significant improvement in Constant scores and shoulder motion with minimal complications. There was no recurrence of posterior instability observed by the time of final follow-up.⁴¹

RSA is a promising treatment for primary glenohumeral arthritis with posterior glenoid bone loss and static posterior subluxation in elderly or less active patients, but the longevity of these implants has yet to be established for younger, more active patients and requires further study.

Conclusion

Reconstruction of the B2 glenoid presents a challenging clinical problem that has been associated with poor clinical outcomes and implant survivorship. The high failure rate from glenoid component loosening and subsequent premature implant failure can be substantially decreased with accurate glenoid component positioning and appropriate correction of the pathologic glenoid retroversion. Careful preoperative planning is essential for accurate preparation and execution of the optimal surgical plan. There are many surgical strategies to address the B2 glenoid, but no consensus on the optimal method exists, as the technique should be uniquely customized to the individual’s pathology and surgeon preference (Table). Cases with mild deformity may be corrected with eccentric reaming and TSA, while the more severe deformities may require posterior glenoid bone grafting and/or augmented implants to restore native version. Finally, the RSA is a reliable option to restore stability and address bone deficiency for the severe B2 glenoid in an older, lower demand patient.

Subscapularis integrity following total shoulder arthroplasty (TSA) is important to maintaining glenohumeral joint stability and functional outcome. In recent years increased emphasis has been placed on the management of the subscapularis during TSA. Options for management of the subscapularis during TSA include tenotomy, release of the tendon from the bone (peel technique), or a lesser tuberosity osteotomy (LTO). Several studies have demonstrated that subscapularis integrity is often impaired with a traditional tenotomy approach.^1,2 Based on these studies, a subscapularis peel or LTO approach have gained popularity.³ This technical article describes a subscapularis peel repair technique that is integrated into a press-fit anatomical short-stem during TSA.

Technique

The repair technique demonstrated in this article features the Univers Apex (Arthrex) humeral stem, but it can be adapted to other stems with features that allow for the incorporation of sutures.

A standard deltopectoral approach is used to gain access to the shoulder. The biceps tendon is released or tenotomized to gain access to the bicipital groove. The rotator interval is then opened beginning at the superior subscapularis by following the course of the anterior side of the proximal biceps and then directing the release toward the base of the coracoid in order to protect the supraspinatus tendon. Next, the subscapularis is sharply released from the lesser tuberosity. The tendon and capsule are released as a unit and a 3-sided release of the subscapularis is performed.

The humeral canal is opened with a reamer and broached to accommodate an appropriately sized press-fit component. A polyethylene glenoid component is placed and then attention is returned to the humerus.

Prior to placement of the humeral stem, 6 No. 2 or No. 5 FiberWire (Arthrex) sutures are pre-placed through suture holes in the stem (Figure 1). Four sutures are passed by hand through the medial calcar component and 2 sutures are placed through holes in the lateral portion of the stem. A 2.0-mm or 2.5-mm drill is used to create 2 holes in the bicipital groove: 1 at the superior aspect of the lesser tuberosity, and 1 at the inferior aspect of the lesser tuberosity (Figure 2A). Prior to impacting the stem, the 4 lateral suture limbs (limbs A through D) are shuttled through the holes in the bicipital groove (Figure 2B). Then the stem is impacted and secured, the final humeral head is placed, the joint is reduced, and the subscapularis is repaired (Figure 2C).

The 4 sutures passing through the medial calcar of the stem result in 8 suture limbs (limbs 1 through 8). Each limb is separately passed through the subscapularis tendon with a free needle, moving obliquely from inferior-medial to superior-lateral (Figure 3). Note: A variation is to pass 2 suture limbs at a time, but this technique has not been biomechanically investigated at the time of this writing.

Prior to tying the sutures, it is helpful to place a stitch between the superolateral corner of the subscapularis and the anterior supraspinatus in order to facilitate reduction. The suture limbs are then tied with a specific sequence to create a suture-bridging construct with 2 additional medial mattress sutures as follows (Figures 4A, 4B):

1 to A

4 to C

5 to B

8 to D

2 to 3

6 to 7

In this technique, each suture limb is tied to a limb from another suture. When the last 2 pairs are tied (2 to 3 and 6 to 7), they are tensioned to remove any slack from the repair and equalize tension within all suture pairs. After the sutures are tied, the rotator interval may be closed with simple sutures if desired. The patient is immobilized in a sling for 4 to 6 weeks. Immediate passive forward flexion is allowed as well as external rotation to 30°. Strengthening is initiated at 8 weeks.

Discussion

The incidence of TSA has increased dramatically in the last decade and is projected to continue in the coming years.⁴ In the majority of cases, TSA leads to improvement in pain and function. However, failures continue to exist. In addition to glenoid loosening, prosthetic instability and rotator cuff insufficiency are the most common causes of failure.⁵ The latter 2 are intimately related since glenohumeral stability depends largely upon the rotator cuff. Therefore, optimization of outcome following TSA depends largely upon maintaining integrity of the rotator cuff. While the incidence of preoperative rotator cuff tears and fatty degeneration of the rotator are not modifiable, the management of the subscapularis is in the hands of the surgeon.

While subscapularis tenotomy has historically been used to access the glenohumeral joint during TSA, this approach is associated with an alarmingly high failure rate. Jackson and colleagues¹ reported that 7 out of 15 (47%) of subscapularis tendons managed with tenotomy during TSA were completely torn on postoperative ultrasound. The patients with postoperative rupture had decreased internal rotation strength and DASH scores (4.6 intact vs. 25 ruptured; P = .04) compared to the patients with an intact tendon. Scalise and colleagues² retrospectively compared a tenotomy approach to a LTO. They reported that 7 out of 15 subscapularis tenotomies were ruptured or attenuated postoperatively. By comparison, 18 out of 20 LTOs were healed. Regardless of approach, functional outcome was higher at 1 year postoperative when the subscapularis was intact.

The high failure rate with tendon-to-tendon healing following tenotomy has led to interest in a subscapularis peel to achieve tendon-to-bone healing or an LTO approach to achieve bone-to-bone healing. Lapner and colleagues³ compared a peel to an LTO in a randomized controlled trial of 87 patients. At 2 years postoperative, there was no difference in functional outcome between the 2 groups.

While both a peel and an LTO approach can be repaired with the technique described in this article, there are advantages to a peel approach. First, a peel approach may be considered more reproducible, particularly for surgeons who do a limited amount of shoulder arthroplasty. Whereas an LTO can vary in size, the subscapularis can nearly always be reproducibly peeled from the lesser tuberosity. Second, this technique uses a short stem, which relies upon proximal fixation. While this approach is bone-preserving, a large osteotomy has the potential to compromise fixation of the stem. Therefore, while one of us (PJD) uses a fleck LTO with a short stem, we advise a peel technique in most cases.

In summary, the subscapularis repair technique described here provides a reproducible and biomechanically sound approach to managing the subscapularis during TSA.

Subscapularis integrity following total shoulder arthroplasty (TSA) is important to maintaining glenohumeral joint stability and functional outcome. In recent years increased emphasis has been placed on the management of the subscapularis during TSA. Options for management of the subscapularis during TSA include tenotomy, release of the tendon from the bone (peel technique), or a lesser tuberosity osteotomy (LTO). Several studies have demonstrated that subscapularis integrity is often impaired with a traditional tenotomy approach.^1,2 Based on these studies, a subscapularis peel or LTO approach have gained popularity.³ This technical article describes a subscapularis peel repair technique that is integrated into a press-fit anatomical short-stem during TSA.

Technique

The repair technique demonstrated in this article features the Univers Apex (Arthrex) humeral stem, but it can be adapted to other stems with features that allow for the incorporation of sutures.

A standard deltopectoral approach is used to gain access to the shoulder. The biceps tendon is released or tenotomized to gain access to the bicipital groove. The rotator interval is then opened beginning at the superior subscapularis by following the course of the anterior side of the proximal biceps and then directing the release toward the base of the coracoid in order to protect the supraspinatus tendon. Next, the subscapularis is sharply released from the lesser tuberosity. The tendon and capsule are released as a unit and a 3-sided release of the subscapularis is performed.

The humeral canal is opened with a reamer and broached to accommodate an appropriately sized press-fit component. A polyethylene glenoid component is placed and then attention is returned to the humerus.

Prior to placement of the humeral stem, 6 No. 2 or No. 5 FiberWire (Arthrex) sutures are pre-placed through suture holes in the stem (Figure 1). Four sutures are passed by hand through the medial calcar component and 2 sutures are placed through holes in the lateral portion of the stem. A 2.0-mm or 2.5-mm drill is used to create 2 holes in the bicipital groove: 1 at the superior aspect of the lesser tuberosity, and 1 at the inferior aspect of the lesser tuberosity (Figure 2A). Prior to impacting the stem, the 4 lateral suture limbs (limbs A through D) are shuttled through the holes in the bicipital groove (Figure 2B). Then the stem is impacted and secured, the final humeral head is placed, the joint is reduced, and the subscapularis is repaired (Figure 2C).

The 4 sutures passing through the medial calcar of the stem result in 8 suture limbs (limbs 1 through 8). Each limb is separately passed through the subscapularis tendon with a free needle, moving obliquely from inferior-medial to superior-lateral (Figure 3). Note: A variation is to pass 2 suture limbs at a time, but this technique has not been biomechanically investigated at the time of this writing.

Prior to tying the sutures, it is helpful to place a stitch between the superolateral corner of the subscapularis and the anterior supraspinatus in order to facilitate reduction. The suture limbs are then tied with a specific sequence to create a suture-bridging construct with 2 additional medial mattress sutures as follows (Figures 4A, 4B):

1 to A

4 to C

5 to B

8 to D

2 to 3

6 to 7

In this technique, each suture limb is tied to a limb from another suture. When the last 2 pairs are tied (2 to 3 and 6 to 7), they are tensioned to remove any slack from the repair and equalize tension within all suture pairs. After the sutures are tied, the rotator interval may be closed with simple sutures if desired. The patient is immobilized in a sling for 4 to 6 weeks. Immediate passive forward flexion is allowed as well as external rotation to 30°. Strengthening is initiated at 8 weeks.

Discussion

The incidence of TSA has increased dramatically in the last decade and is projected to continue in the coming years.⁴ In the majority of cases, TSA leads to improvement in pain and function. However, failures continue to exist. In addition to glenoid loosening, prosthetic instability and rotator cuff insufficiency are the most common causes of failure.⁵ The latter 2 are intimately related since glenohumeral stability depends largely upon the rotator cuff. Therefore, optimization of outcome following TSA depends largely upon maintaining integrity of the rotator cuff. While the incidence of preoperative rotator cuff tears and fatty degeneration of the rotator are not modifiable, the management of the subscapularis is in the hands of the surgeon.

While subscapularis tenotomy has historically been used to access the glenohumeral joint during TSA, this approach is associated with an alarmingly high failure rate. Jackson and colleagues¹ reported that 7 out of 15 (47%) of subscapularis tendons managed with tenotomy during TSA were completely torn on postoperative ultrasound. The patients with postoperative rupture had decreased internal rotation strength and DASH scores (4.6 intact vs. 25 ruptured; P = .04) compared to the patients with an intact tendon. Scalise and colleagues² retrospectively compared a tenotomy approach to a LTO. They reported that 7 out of 15 subscapularis tenotomies were ruptured or attenuated postoperatively. By comparison, 18 out of 20 LTOs were healed. Regardless of approach, functional outcome was higher at 1 year postoperative when the subscapularis was intact.

The high failure rate with tendon-to-tendon healing following tenotomy has led to interest in a subscapularis peel to achieve tendon-to-bone healing or an LTO approach to achieve bone-to-bone healing. Lapner and colleagues³ compared a peel to an LTO in a randomized controlled trial of 87 patients. At 2 years postoperative, there was no difference in functional outcome between the 2 groups.

While both a peel and an LTO approach can be repaired with the technique described in this article, there are advantages to a peel approach. First, a peel approach may be considered more reproducible, particularly for surgeons who do a limited amount of shoulder arthroplasty. Whereas an LTO can vary in size, the subscapularis can nearly always be reproducibly peeled from the lesser tuberosity. Second, this technique uses a short stem, which relies upon proximal fixation. While this approach is bone-preserving, a large osteotomy has the potential to compromise fixation of the stem. Therefore, while one of us (PJD) uses a fleck LTO with a short stem, we advise a peel technique in most cases.

In summary, the subscapularis repair technique described here provides a reproducible and biomechanically sound approach to managing the subscapularis during TSA.

Subscapularis integrity following total shoulder arthroplasty (TSA) is important to maintaining glenohumeral joint stability and functional outcome. In recent years increased emphasis has been placed on the management of the subscapularis during TSA. Options for management of the subscapularis during TSA include tenotomy, release of the tendon from the bone (peel technique), or a lesser tuberosity osteotomy (LTO). Several studies have demonstrated that subscapularis integrity is often impaired with a traditional tenotomy approach.^1,2 Based on these studies, a subscapularis peel or LTO approach have gained popularity.³ This technical article describes a subscapularis peel repair technique that is integrated into a press-fit anatomical short-stem during TSA.

Technique

The repair technique demonstrated in this article features the Univers Apex (Arthrex) humeral stem, but it can be adapted to other stems with features that allow for the incorporation of sutures.

A standard deltopectoral approach is used to gain access to the shoulder. The biceps tendon is released or tenotomized to gain access to the bicipital groove. The rotator interval is then opened beginning at the superior subscapularis by following the course of the anterior side of the proximal biceps and then directing the release toward the base of the coracoid in order to protect the supraspinatus tendon. Next, the subscapularis is sharply released from the lesser tuberosity. The tendon and capsule are released as a unit and a 3-sided release of the subscapularis is performed.

The humeral canal is opened with a reamer and broached to accommodate an appropriately sized press-fit component. A polyethylene glenoid component is placed and then attention is returned to the humerus.

Prior to placement of the humeral stem, 6 No. 2 or No. 5 FiberWire (Arthrex) sutures are pre-placed through suture holes in the stem (Figure 1). Four sutures are passed by hand through the medial calcar component and 2 sutures are placed through holes in the lateral portion of the stem. A 2.0-mm or 2.5-mm drill is used to create 2 holes in the bicipital groove: 1 at the superior aspect of the lesser tuberosity, and 1 at the inferior aspect of the lesser tuberosity (Figure 2A). Prior to impacting the stem, the 4 lateral suture limbs (limbs A through D) are shuttled through the holes in the bicipital groove (Figure 2B). Then the stem is impacted and secured, the final humeral head is placed, the joint is reduced, and the subscapularis is repaired (Figure 2C).

The 4 sutures passing through the medial calcar of the stem result in 8 suture limbs (limbs 1 through 8). Each limb is separately passed through the subscapularis tendon with a free needle, moving obliquely from inferior-medial to superior-lateral (Figure 3). Note: A variation is to pass 2 suture limbs at a time, but this technique has not been biomechanically investigated at the time of this writing.

Prior to tying the sutures, it is helpful to place a stitch between the superolateral corner of the subscapularis and the anterior supraspinatus in order to facilitate reduction. The suture limbs are then tied with a specific sequence to create a suture-bridging construct with 2 additional medial mattress sutures as follows (Figures 4A, 4B):

1 to A

4 to C

5 to B

8 to D

2 to 3

6 to 7

In this technique, each suture limb is tied to a limb from another suture. When the last 2 pairs are tied (2 to 3 and 6 to 7), they are tensioned to remove any slack from the repair and equalize tension within all suture pairs. After the sutures are tied, the rotator interval may be closed with simple sutures if desired. The patient is immobilized in a sling for 4 to 6 weeks. Immediate passive forward flexion is allowed as well as external rotation to 30°. Strengthening is initiated at 8 weeks.

Discussion

The incidence of TSA has increased dramatically in the last decade and is projected to continue in the coming years.⁴ In the majority of cases, TSA leads to improvement in pain and function. However, failures continue to exist. In addition to glenoid loosening, prosthetic instability and rotator cuff insufficiency are the most common causes of failure.⁵ The latter 2 are intimately related since glenohumeral stability depends largely upon the rotator cuff. Therefore, optimization of outcome following TSA depends largely upon maintaining integrity of the rotator cuff. While the incidence of preoperative rotator cuff tears and fatty degeneration of the rotator are not modifiable, the management of the subscapularis is in the hands of the surgeon.

While subscapularis tenotomy has historically been used to access the glenohumeral joint during TSA, this approach is associated with an alarmingly high failure rate. Jackson and colleagues¹ reported that 7 out of 15 (47%) of subscapularis tendons managed with tenotomy during TSA were completely torn on postoperative ultrasound. The patients with postoperative rupture had decreased internal rotation strength and DASH scores (4.6 intact vs. 25 ruptured; P = .04) compared to the patients with an intact tendon. Scalise and colleagues² retrospectively compared a tenotomy approach to a LTO. They reported that 7 out of 15 subscapularis tenotomies were ruptured or attenuated postoperatively. By comparison, 18 out of 20 LTOs were healed. Regardless of approach, functional outcome was higher at 1 year postoperative when the subscapularis was intact.

The high failure rate with tendon-to-tendon healing following tenotomy has led to interest in a subscapularis peel to achieve tendon-to-bone healing or an LTO approach to achieve bone-to-bone healing. Lapner and colleagues³ compared a peel to an LTO in a randomized controlled trial of 87 patients. At 2 years postoperative, there was no difference in functional outcome between the 2 groups.

While both a peel and an LTO approach can be repaired with the technique described in this article, there are advantages to a peel approach. First, a peel approach may be considered more reproducible, particularly for surgeons who do a limited amount of shoulder arthroplasty. Whereas an LTO can vary in size, the subscapularis can nearly always be reproducibly peeled from the lesser tuberosity. Second, this technique uses a short stem, which relies upon proximal fixation. While this approach is bone-preserving, a large osteotomy has the potential to compromise fixation of the stem. Therefore, while one of us (PJD) uses a fleck LTO with a short stem, we advise a peel technique in most cases.

In summary, the subscapularis repair technique described here provides a reproducible and biomechanically sound approach to managing the subscapularis during TSA.