User login
Does platelet-rich plasma improve patellar tendinopathy symptoms?
Evidence summary
Symptoms improve with PRP—but not significantly
A 2014 double-blind RCT (n = 23) explored recovery outcomes in patients with patellar tendinopathy who received either 1 injection of leukocyte-rich PRP or ultrasound-guided dry needling.1 Both groups also completed standardized eccentric exercises. Participants were predominantly men, ages ≥ 18 years. Symptomatic improvement was assessed using the Victorian Institute of Sport Assessment–Patella (VISA-P), an 8-item subjective questionnaire of functionality with a range of 0 to 100, with 100 as the maximum score for an asymptomatic individual.
At 12 weeks posttreatment, VISA-P scores improved in both groups. However, the improvement in the dry needling group was not statistically significant (5.2 points; 95% CI, –2.2 to 12.6; P = .20), while in the PRP group it was statistically significant (25.4 points; 95% CI, 10.3 to 40.6; P = .01). At ≥ 26 weeks, statistically significant improvement was observed in both treatment groups: scores improved by 33.2 points (95% CI, 24.1 to 42.4; P = .001) in the dry needling group and by 28.9 points (95% CI, 11.4 to 46.3; P = .01) in the PRP group. However, the difference between the groups’ VISA-P scores at ≥ 26 weeks was not significant (P = .66).1
No significant differences observed for PRP vs placebo or physical therapy
A 2019 single-blind RCT (n = 57) involved patients who were treated with 1 injection of either leukocyte-rich PRP, leukocyte-poor PRP, or saline, all in combination with 6 weeks of physical therapy.2 Participants were predominantly men, ages 18 to 50 years, and engaged in recreational sporting activities. There was no statistically significant difference in mean change in VISA-P score at any timepoint of the 2-year study period. P values were not reported.2
A 2010 RCT (n = 31) compared PRP (unspecified whether leukocyte-rich or -poor) in combination with physical therapy to physical therapy alone.3 Groups were matched for sex, age, and sports activity level; patients in the PRP group were required to have failed previous treatment, while control subjects must not have received any treatment for at least 2 months. Subjects were evaluated pretreatment, immediately posttreatment, and 6 months posttreatment. Clinical evaluation was aided by use of the Tegner activity score, a 1-item score that grades activity level on a scale of 0 to 10; the EuroQol-visual analog scale (EQ-VAS), which evaluates subjective rating of overall health; and pain level scores.
At 6 months posttreatment, no statistically significant differences were observed between groups in EQ-VAS and pain level scores. However, Tegner activity scores among PRP recipients showed significant percent improvement over controls at 6 months posttreatment (39% vs 20%; P = .048).3
Recommendations from others
Currently, national orthopedic and professional athletic medical associations have recommended that further research be conducted in order to make a strong statement in favor of or against PRP.4,5
Editor’s takeaway
Existing data regarding PRP fails, again, to show consistent benefits. These small sample sizes, inconsistent comparators, and heterogeneous results limit our certainty. This lack of quality evidence does not prove a lack of effect, but it raises serious doubts.
1. Dragoo JL, Wasterlain AS, Braun HJ, et al. Platelet-rich plasma as a treatment for patellar tendinopathy: a double-blind, randomized controlled trial. Am J Sports Med. 2014;42:610-618. doi: 10.1177/0363546513518416
2. Scott A, LaPrade R, Harmon K, et al. Platelet-rich plasma for patellar tendinopathy: a randomized controlled trial of leukocyte-rich PRP or leukocyte-poor PRP versus saline. Am J Sports Med. 2019;47:1654-1661. doi: 10.1177/0363546519837954
3. Filardo G, Kon E, Villa S Della, et al. Use of platelet-rich plasma for the treatment of refractory jumper’s knee. Int Orthop. 2010;34:909. doi: 10.1007/s00264-009-0845-7
4. LaPrade R, Dragoo J, Koh J, et al. AAOS Research Symposium updates and consensus: biologic treatment of orthopaedic injuries. J Am Acad Orthop Surg. 2016;24:e62-e78. doi: 10.5435/JAAOS-D-16-00086
5. Rodeo SA, Bedi A. 2019-2020 NFL and NFL Physician Society orthobiologics consensus statement. Sports Health. 2020;12:58-60. doi: 10.1177/1941738119889013
Evidence summary
Symptoms improve with PRP—but not significantly
A 2014 double-blind RCT (n = 23) explored recovery outcomes in patients with patellar tendinopathy who received either 1 injection of leukocyte-rich PRP or ultrasound-guided dry needling.1 Both groups also completed standardized eccentric exercises. Participants were predominantly men, ages ≥ 18 years. Symptomatic improvement was assessed using the Victorian Institute of Sport Assessment–Patella (VISA-P), an 8-item subjective questionnaire of functionality with a range of 0 to 100, with 100 as the maximum score for an asymptomatic individual.
At 12 weeks posttreatment, VISA-P scores improved in both groups. However, the improvement in the dry needling group was not statistically significant (5.2 points; 95% CI, –2.2 to 12.6; P = .20), while in the PRP group it was statistically significant (25.4 points; 95% CI, 10.3 to 40.6; P = .01). At ≥ 26 weeks, statistically significant improvement was observed in both treatment groups: scores improved by 33.2 points (95% CI, 24.1 to 42.4; P = .001) in the dry needling group and by 28.9 points (95% CI, 11.4 to 46.3; P = .01) in the PRP group. However, the difference between the groups’ VISA-P scores at ≥ 26 weeks was not significant (P = .66).1
No significant differences observed for PRP vs placebo or physical therapy
A 2019 single-blind RCT (n = 57) involved patients who were treated with 1 injection of either leukocyte-rich PRP, leukocyte-poor PRP, or saline, all in combination with 6 weeks of physical therapy.2 Participants were predominantly men, ages 18 to 50 years, and engaged in recreational sporting activities. There was no statistically significant difference in mean change in VISA-P score at any timepoint of the 2-year study period. P values were not reported.2
A 2010 RCT (n = 31) compared PRP (unspecified whether leukocyte-rich or -poor) in combination with physical therapy to physical therapy alone.3 Groups were matched for sex, age, and sports activity level; patients in the PRP group were required to have failed previous treatment, while control subjects must not have received any treatment for at least 2 months. Subjects were evaluated pretreatment, immediately posttreatment, and 6 months posttreatment. Clinical evaluation was aided by use of the Tegner activity score, a 1-item score that grades activity level on a scale of 0 to 10; the EuroQol-visual analog scale (EQ-VAS), which evaluates subjective rating of overall health; and pain level scores.
At 6 months posttreatment, no statistically significant differences were observed between groups in EQ-VAS and pain level scores. However, Tegner activity scores among PRP recipients showed significant percent improvement over controls at 6 months posttreatment (39% vs 20%; P = .048).3
Recommendations from others
Currently, national orthopedic and professional athletic medical associations have recommended that further research be conducted in order to make a strong statement in favor of or against PRP.4,5
Editor’s takeaway
Existing data regarding PRP fails, again, to show consistent benefits. These small sample sizes, inconsistent comparators, and heterogeneous results limit our certainty. This lack of quality evidence does not prove a lack of effect, but it raises serious doubts.
Evidence summary
Symptoms improve with PRP—but not significantly
A 2014 double-blind RCT (n = 23) explored recovery outcomes in patients with patellar tendinopathy who received either 1 injection of leukocyte-rich PRP or ultrasound-guided dry needling.1 Both groups also completed standardized eccentric exercises. Participants were predominantly men, ages ≥ 18 years. Symptomatic improvement was assessed using the Victorian Institute of Sport Assessment–Patella (VISA-P), an 8-item subjective questionnaire of functionality with a range of 0 to 100, with 100 as the maximum score for an asymptomatic individual.
At 12 weeks posttreatment, VISA-P scores improved in both groups. However, the improvement in the dry needling group was not statistically significant (5.2 points; 95% CI, –2.2 to 12.6; P = .20), while in the PRP group it was statistically significant (25.4 points; 95% CI, 10.3 to 40.6; P = .01). At ≥ 26 weeks, statistically significant improvement was observed in both treatment groups: scores improved by 33.2 points (95% CI, 24.1 to 42.4; P = .001) in the dry needling group and by 28.9 points (95% CI, 11.4 to 46.3; P = .01) in the PRP group. However, the difference between the groups’ VISA-P scores at ≥ 26 weeks was not significant (P = .66).1
No significant differences observed for PRP vs placebo or physical therapy
A 2019 single-blind RCT (n = 57) involved patients who were treated with 1 injection of either leukocyte-rich PRP, leukocyte-poor PRP, or saline, all in combination with 6 weeks of physical therapy.2 Participants were predominantly men, ages 18 to 50 years, and engaged in recreational sporting activities. There was no statistically significant difference in mean change in VISA-P score at any timepoint of the 2-year study period. P values were not reported.2
A 2010 RCT (n = 31) compared PRP (unspecified whether leukocyte-rich or -poor) in combination with physical therapy to physical therapy alone.3 Groups were matched for sex, age, and sports activity level; patients in the PRP group were required to have failed previous treatment, while control subjects must not have received any treatment for at least 2 months. Subjects were evaluated pretreatment, immediately posttreatment, and 6 months posttreatment. Clinical evaluation was aided by use of the Tegner activity score, a 1-item score that grades activity level on a scale of 0 to 10; the EuroQol-visual analog scale (EQ-VAS), which evaluates subjective rating of overall health; and pain level scores.
At 6 months posttreatment, no statistically significant differences were observed between groups in EQ-VAS and pain level scores. However, Tegner activity scores among PRP recipients showed significant percent improvement over controls at 6 months posttreatment (39% vs 20%; P = .048).3
Recommendations from others
Currently, national orthopedic and professional athletic medical associations have recommended that further research be conducted in order to make a strong statement in favor of or against PRP.4,5
Editor’s takeaway
Existing data regarding PRP fails, again, to show consistent benefits. These small sample sizes, inconsistent comparators, and heterogeneous results limit our certainty. This lack of quality evidence does not prove a lack of effect, but it raises serious doubts.
1. Dragoo JL, Wasterlain AS, Braun HJ, et al. Platelet-rich plasma as a treatment for patellar tendinopathy: a double-blind, randomized controlled trial. Am J Sports Med. 2014;42:610-618. doi: 10.1177/0363546513518416
2. Scott A, LaPrade R, Harmon K, et al. Platelet-rich plasma for patellar tendinopathy: a randomized controlled trial of leukocyte-rich PRP or leukocyte-poor PRP versus saline. Am J Sports Med. 2019;47:1654-1661. doi: 10.1177/0363546519837954
3. Filardo G, Kon E, Villa S Della, et al. Use of platelet-rich plasma for the treatment of refractory jumper’s knee. Int Orthop. 2010;34:909. doi: 10.1007/s00264-009-0845-7
4. LaPrade R, Dragoo J, Koh J, et al. AAOS Research Symposium updates and consensus: biologic treatment of orthopaedic injuries. J Am Acad Orthop Surg. 2016;24:e62-e78. doi: 10.5435/JAAOS-D-16-00086
5. Rodeo SA, Bedi A. 2019-2020 NFL and NFL Physician Society orthobiologics consensus statement. Sports Health. 2020;12:58-60. doi: 10.1177/1941738119889013
1. Dragoo JL, Wasterlain AS, Braun HJ, et al. Platelet-rich plasma as a treatment for patellar tendinopathy: a double-blind, randomized controlled trial. Am J Sports Med. 2014;42:610-618. doi: 10.1177/0363546513518416
2. Scott A, LaPrade R, Harmon K, et al. Platelet-rich plasma for patellar tendinopathy: a randomized controlled trial of leukocyte-rich PRP or leukocyte-poor PRP versus saline. Am J Sports Med. 2019;47:1654-1661. doi: 10.1177/0363546519837954
3. Filardo G, Kon E, Villa S Della, et al. Use of platelet-rich plasma for the treatment of refractory jumper’s knee. Int Orthop. 2010;34:909. doi: 10.1007/s00264-009-0845-7
4. LaPrade R, Dragoo J, Koh J, et al. AAOS Research Symposium updates and consensus: biologic treatment of orthopaedic injuries. J Am Acad Orthop Surg. 2016;24:e62-e78. doi: 10.5435/JAAOS-D-16-00086
5. Rodeo SA, Bedi A. 2019-2020 NFL and NFL Physician Society orthobiologics consensus statement. Sports Health. 2020;12:58-60. doi: 10.1177/1941738119889013
EVIDENCE-BASED ANSWER:
IT’S UNCLEAR. High-quality data have not consistently established the effectiveness of platelet-rich plasma (PRP) injections to improve symptomatic recovery in patellar tendinopathy, compared to placebo (strength of recommendation [SOR]: A, based on 3 small randomized controlled trials [RCTs]). The 3 small RCTs included only 111 patients, total. One found no evidence of significant improvement with PRP compared to controls. The other 2 studies showed mixed results, with different outcome measures favoring different treatment groups and heterogeneous results depending on follow-up duration.
Which injections are effective for lateral epicondylitis?
EVIDENCE SUMMARY
Neither corticosteroids nor platelet-rich plasma are superior to placebo
A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.1 In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.2
In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone follow-up. No functional assessments were reported at 6 months.3
The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.4
The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.5
Platelet-rich plasma. A meta-analysis6 of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.
Corticosteroids and PRP. A 2013 3-armed RCT7 (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.
Botulinum toxin shows modest pain improvement, but …
A 2017 meta-analysis8 of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).
Continue to: Prolotherapy needs further study
Prolotherapy needs further study
A 2008 RCT9 of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.
Hyaluronic acid improves pain, but not enough
A 2010 double-blind RCT10 (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.
Autologous blood has no advantage over placebo
The only RCT of autologous blood compared to saline injections11 included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.
Editor’s takeaway
Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Lindenhovius A, Henket M, Gilligan BP, et al. Injection of dexamethasone versus placebo for lateral elbow pain: a prospective, double-blind, randomized clinical trial. J Hand Surg Am. 2008;33:909-919. doi: 10.1016/j.jhsa.2008.02.004
3. Newcomer KL, Laskowski ER, Idank DM, et al. Corticosteroid injection in early treatment of lateral epicondylitis. Clin J Sport Med. 2001;11:214-222. doi: 10.1097/00042752-200110000-00002
4. Coombes BK, Bisset L, Brooks P, et al. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013;309:461-469. doi: 10.1001/jama.2013.129
5. Altay T, Gunal I, Ozturk H. Local injection treatment for lateral epicondylitis. Clin Orthop Relat Res. 2002;398:127-130.
6. Simental-Mendía M, Vilchez-Cavazos F, Álvarez-Villalobos N, et al. Clinical efficacy of platelet-rich plasma in the treatment of lateral epicondylitis: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Clin Rheumatol. 2020;39:2255-2265. doi: 10.1007/s10067-020-05000-y
7. Krogh T, Fredberg U, Stengaard-Pedersen K, et al. Treatment of lateral epicondylitis with platelet-rich-plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2013;41:625-635. doi:10.1177/0363546512472975
8. Lin Y, Wu W, Hsu Y, et al. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis. Clin Rehabil. 2017;32:131-145. doi:10.1177/0269215517702517
9. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sports Med. 2008;18:248-254. doi: 10.1097/JSM.0b013e318170fc87
10. Petrella R, Cogliano A, Decaria J, et al. Management of tennis elbow with sodium hyaluronate periarticular injections. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:4. doi: 10.1186/1758-2555-2-4
11. Wolf JM, Ozer K, Scott F, et al. Comparison of autologous blood, corticosteroid, and saline injection in the treatment of lateral epicondylitis: a prospective, randomized, controlled multicenter study. J Hand Surg Am. 2011;36:1269-1272. doi: 10.1016/j.jhsa.2011.05.014
EVIDENCE SUMMARY
Neither corticosteroids nor platelet-rich plasma are superior to placebo
A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.1 In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.2
In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone follow-up. No functional assessments were reported at 6 months.3
The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.4
The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.5
Platelet-rich plasma. A meta-analysis6 of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.
Corticosteroids and PRP. A 2013 3-armed RCT7 (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.
Botulinum toxin shows modest pain improvement, but …
A 2017 meta-analysis8 of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).
Continue to: Prolotherapy needs further study
Prolotherapy needs further study
A 2008 RCT9 of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.
Hyaluronic acid improves pain, but not enough
A 2010 double-blind RCT10 (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.
Autologous blood has no advantage over placebo
The only RCT of autologous blood compared to saline injections11 included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.
Editor’s takeaway
Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.
EVIDENCE SUMMARY
Neither corticosteroids nor platelet-rich plasma are superior to placebo
A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.1 In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.2
In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone follow-up. No functional assessments were reported at 6 months.3
The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.4
The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.5
Platelet-rich plasma. A meta-analysis6 of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.
Corticosteroids and PRP. A 2013 3-armed RCT7 (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.
Botulinum toxin shows modest pain improvement, but …
A 2017 meta-analysis8 of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).
Continue to: Prolotherapy needs further study
Prolotherapy needs further study
A 2008 RCT9 of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.
Hyaluronic acid improves pain, but not enough
A 2010 double-blind RCT10 (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.
Autologous blood has no advantage over placebo
The only RCT of autologous blood compared to saline injections11 included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.
Editor’s takeaway
Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Lindenhovius A, Henket M, Gilligan BP, et al. Injection of dexamethasone versus placebo for lateral elbow pain: a prospective, double-blind, randomized clinical trial. J Hand Surg Am. 2008;33:909-919. doi: 10.1016/j.jhsa.2008.02.004
3. Newcomer KL, Laskowski ER, Idank DM, et al. Corticosteroid injection in early treatment of lateral epicondylitis. Clin J Sport Med. 2001;11:214-222. doi: 10.1097/00042752-200110000-00002
4. Coombes BK, Bisset L, Brooks P, et al. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013;309:461-469. doi: 10.1001/jama.2013.129
5. Altay T, Gunal I, Ozturk H. Local injection treatment for lateral epicondylitis. Clin Orthop Relat Res. 2002;398:127-130.
6. Simental-Mendía M, Vilchez-Cavazos F, Álvarez-Villalobos N, et al. Clinical efficacy of platelet-rich plasma in the treatment of lateral epicondylitis: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Clin Rheumatol. 2020;39:2255-2265. doi: 10.1007/s10067-020-05000-y
7. Krogh T, Fredberg U, Stengaard-Pedersen K, et al. Treatment of lateral epicondylitis with platelet-rich-plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2013;41:625-635. doi:10.1177/0363546512472975
8. Lin Y, Wu W, Hsu Y, et al. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis. Clin Rehabil. 2017;32:131-145. doi:10.1177/0269215517702517
9. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sports Med. 2008;18:248-254. doi: 10.1097/JSM.0b013e318170fc87
10. Petrella R, Cogliano A, Decaria J, et al. Management of tennis elbow with sodium hyaluronate periarticular injections. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:4. doi: 10.1186/1758-2555-2-4
11. Wolf JM, Ozer K, Scott F, et al. Comparison of autologous blood, corticosteroid, and saline injection in the treatment of lateral epicondylitis: a prospective, randomized, controlled multicenter study. J Hand Surg Am. 2011;36:1269-1272. doi: 10.1016/j.jhsa.2011.05.014
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Lindenhovius A, Henket M, Gilligan BP, et al. Injection of dexamethasone versus placebo for lateral elbow pain: a prospective, double-blind, randomized clinical trial. J Hand Surg Am. 2008;33:909-919. doi: 10.1016/j.jhsa.2008.02.004
3. Newcomer KL, Laskowski ER, Idank DM, et al. Corticosteroid injection in early treatment of lateral epicondylitis. Clin J Sport Med. 2001;11:214-222. doi: 10.1097/00042752-200110000-00002
4. Coombes BK, Bisset L, Brooks P, et al. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013;309:461-469. doi: 10.1001/jama.2013.129
5. Altay T, Gunal I, Ozturk H. Local injection treatment for lateral epicondylitis. Clin Orthop Relat Res. 2002;398:127-130.
6. Simental-Mendía M, Vilchez-Cavazos F, Álvarez-Villalobos N, et al. Clinical efficacy of platelet-rich plasma in the treatment of lateral epicondylitis: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Clin Rheumatol. 2020;39:2255-2265. doi: 10.1007/s10067-020-05000-y
7. Krogh T, Fredberg U, Stengaard-Pedersen K, et al. Treatment of lateral epicondylitis with platelet-rich-plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2013;41:625-635. doi:10.1177/0363546512472975
8. Lin Y, Wu W, Hsu Y, et al. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis. Clin Rehabil. 2017;32:131-145. doi:10.1177/0269215517702517
9. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sports Med. 2008;18:248-254. doi: 10.1097/JSM.0b013e318170fc87
10. Petrella R, Cogliano A, Decaria J, et al. Management of tennis elbow with sodium hyaluronate periarticular injections. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:4. doi: 10.1186/1758-2555-2-4
11. Wolf JM, Ozer K, Scott F, et al. Comparison of autologous blood, corticosteroid, and saline injection in the treatment of lateral epicondylitis: a prospective, randomized, controlled multicenter study. J Hand Surg Am. 2011;36:1269-1272. doi: 10.1016/j.jhsa.2011.05.014
EVIDENCE-BASED ANSWER:
Placebo injections actually improve lateral epicondylitis at high rates. No other injections convincingly improve it better than placebo.
Corticosteroid injection is not superior to saline or anesthetic injection (strength of recommendation [SOR] A, systematic review of randomized controlled trials [RCTs]). Platelet-rich plasma (PRP) injection is not superior to saline injection (SOR A, meta-analysis of RCTs).
Botulinum toxin injection, compared to saline injection, modestly improved pain in lateral epicondylitis, but with short-term grip-strength weakness (SOR A, meta-analysis of RCTs). Prolotherapy injection, compared to saline injection, improved pain at 16-week, but not at 8-week, follow-up (SOR B, one small pilot RCT).
Hyaluronic acid injection, compared to saline injection, resulted in a statistically significant pain reduction (6%) but did not achieve the minimum clinically important difference (SOR B, single RCT). Autologous blood injection, compared to saline injection, did not improve disability ratings (SOR B, one small RCT).