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Is intra-articular platelet-rich plasma injection an effective treatment for knee OA?
EVIDENCE SUMMARY
PRP vs placebo. Three RCTs compared PRP with saline placebo injections and 2 found that PRP improved the Western Ontario and McMaster Universities Arthritis Index (WOMAC, a standardized scale assessing knee pain, function, and stiffness) by 40% to 70%; the third found 24% to 32% improvements in the EuroQol visual analog scale (EQ-VAS) scores at 6 months1-3 (TABLE1-12).
The first 2 studies enrolled patients (mean age early 60s, approximately 50% women) with clinically and radiographically evaluated knee OA of mostly moderate severity (baseline WOMAC scores about 50).1,2 Investigators in the first RCT injected PRP once in one subgroup and twice in another subgroup, compared with a single injection of saline in a third subgroup.1 They gave 3 weekly injections of PRP or saline in the second RCT.2
The third study enrolled mainly patients with early osteoarthritis (mean age early 50s, slightly more women). Investigators injected PRP 3 times in one subgroup and once (plus 2 saline injections) in another, compared with 3 saline injections, and evaluated patients at baseline and 6 months.3
PRP vs HA. Nine RCTs compared PRP with HA injections. Six studies (673 patients) found no significant difference; 3 studies (376 patients) found that PRP improved standardized knee assessment scores by 35% to 40% at 24-48 weeks.7,8,10 All studies enrolled patients (mean age early 60s, approximately 50% women) with clinically and radiographically evaluated knee OA of mostly moderate severity. In 7 RCTs, 4-6,9-12 investigators injected PRP or HA weekly for 3 weeks, in one RCT8 they gave 4 weekly injections, and in one7they gave 2 PRP injections separated by 4 weeks.
Three RCTs used the International Knee Documentation Committee (IKDC) score, considered the most reliable standardized scoring system, which quantifies subjective symptoms (pain, stiffness, swelling, giving way), activity (climbing stairs, rising from a chair, squatting, jumping), and function pre- and postintervention.5,9,12 All 3 studies using the IKDC found no difference between PRP and HA injections. Most RCTs used the WOMAC standardized scale, scoring 5 items for pain, 2 for stiffness, and 17 for function.1,2,4,6-8.10
Risk for bias
A systematic review13 that evaluated methodologic quality of the 3 studies comparing PRP with placebo rated 21,3 at high risk of bias and one2 at moderate risk. Another meta-analysis14 performed a quality assessment including 4 of the 9 RCTs,8-10,12 comparing PRP with HA and concluded that 3 had a high risk of bias; the fourth RCT had a moderate risk. No independent quality assessments of the other RCTs were available.4-7,11
RECOMMENDATIONS
The American Academy of Orthopaedic Surgeons doesn’t recommend for or against PRP injections because of insufficient evidence and strongly recommends against HA injections based on multiple RCTs of moderate quality that found no difference between HA and placebo.15
1. Patel S, Dhillon MS, Aggarwal S, et al. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41:356-364.
2. Smith PA. Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee arthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med. 2016;44:884-891.
3. Gorelli G, Gormelli CA, Ataoglu B, et al. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2015;25:958-965.
4. Cole BJ, Karas V, Hussey K, et al. Hyaluronic acid versus platelet-rich plasma: a prospective double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med. 2016;45:339-346.
5. Filardo G, Di Matteo B, Di Martino A, et al. Platelet-rich intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015;43:1575-1582.
6. Sanchez M, Fiz N, Azofra J, et al. A randomized clinical trial evaluating plasma rich in growth factors (PGRF-endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy: J Arth and Related Surg. 2012;28:1070-1078.
7. Raeissadat SA, Rayegani SM, Hassanabadi H, et al. Knee osteoarthritis injection choices: platelet-rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights: Arth Musc Dis. 2015;8:1-8.
8. Cerza F, Carni S, Carcangiu A, et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40:2822-2827.
9. Filardo G, Kon E, Di Martino B, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskeletal Disorders. 2012;13:229-236.
10. Vaquerizo V, Plasencia MA, Arribas I, et al. Comparison of intra-articular injections of plasma rich in growth factors (PGRF-endoret) versus durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy: J Arth and Related Surg. 2013;29:1635-1643.
11. Montanez-Heredia E, Irizar S, Huertas PJ, et al. Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritis knee pain: a randomized clinical trial in the context of the Spanish national health care system. Intl J Molec Sci. 2016;17:1064-1077.
12. Li M, Zhang C, Ai Z, et al. Therapeutic effectiveness of intra-knee articular injections of platelet-rich plasma on knee articular cartilage degeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 25:1192-11966. (Article published in Chinese with abstract in English.)
13. Shen L, Yuan T, Chen S, et al. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Ortho Surg Res. 2017;12:16.
14. Laudy ABM, Bakker EWP, Rekers M, et al. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015;49:657-672.
15. American Academy of Orthopaedic Surgeons. Clinical practice guideline on the treatment of osteoarthritis of the knee, 2nd ed. www.aaos.org/cc_files/aaosorg/research/guidelines/treatmentofosteoarthritisofthekneeguideline.pdf. Published May 2013. Accessed February 22, 2019.
EVIDENCE SUMMARY
PRP vs placebo. Three RCTs compared PRP with saline placebo injections and 2 found that PRP improved the Western Ontario and McMaster Universities Arthritis Index (WOMAC, a standardized scale assessing knee pain, function, and stiffness) by 40% to 70%; the third found 24% to 32% improvements in the EuroQol visual analog scale (EQ-VAS) scores at 6 months1-3 (TABLE1-12).
The first 2 studies enrolled patients (mean age early 60s, approximately 50% women) with clinically and radiographically evaluated knee OA of mostly moderate severity (baseline WOMAC scores about 50).1,2 Investigators in the first RCT injected PRP once in one subgroup and twice in another subgroup, compared with a single injection of saline in a third subgroup.1 They gave 3 weekly injections of PRP or saline in the second RCT.2
The third study enrolled mainly patients with early osteoarthritis (mean age early 50s, slightly more women). Investigators injected PRP 3 times in one subgroup and once (plus 2 saline injections) in another, compared with 3 saline injections, and evaluated patients at baseline and 6 months.3
PRP vs HA. Nine RCTs compared PRP with HA injections. Six studies (673 patients) found no significant difference; 3 studies (376 patients) found that PRP improved standardized knee assessment scores by 35% to 40% at 24-48 weeks.7,8,10 All studies enrolled patients (mean age early 60s, approximately 50% women) with clinically and radiographically evaluated knee OA of mostly moderate severity. In 7 RCTs, 4-6,9-12 investigators injected PRP or HA weekly for 3 weeks, in one RCT8 they gave 4 weekly injections, and in one7they gave 2 PRP injections separated by 4 weeks.
Three RCTs used the International Knee Documentation Committee (IKDC) score, considered the most reliable standardized scoring system, which quantifies subjective symptoms (pain, stiffness, swelling, giving way), activity (climbing stairs, rising from a chair, squatting, jumping), and function pre- and postintervention.5,9,12 All 3 studies using the IKDC found no difference between PRP and HA injections. Most RCTs used the WOMAC standardized scale, scoring 5 items for pain, 2 for stiffness, and 17 for function.1,2,4,6-8.10
Risk for bias
A systematic review13 that evaluated methodologic quality of the 3 studies comparing PRP with placebo rated 21,3 at high risk of bias and one2 at moderate risk. Another meta-analysis14 performed a quality assessment including 4 of the 9 RCTs,8-10,12 comparing PRP with HA and concluded that 3 had a high risk of bias; the fourth RCT had a moderate risk. No independent quality assessments of the other RCTs were available.4-7,11
RECOMMENDATIONS
The American Academy of Orthopaedic Surgeons doesn’t recommend for or against PRP injections because of insufficient evidence and strongly recommends against HA injections based on multiple RCTs of moderate quality that found no difference between HA and placebo.15
EVIDENCE SUMMARY
PRP vs placebo. Three RCTs compared PRP with saline placebo injections and 2 found that PRP improved the Western Ontario and McMaster Universities Arthritis Index (WOMAC, a standardized scale assessing knee pain, function, and stiffness) by 40% to 70%; the third found 24% to 32% improvements in the EuroQol visual analog scale (EQ-VAS) scores at 6 months1-3 (TABLE1-12).
The first 2 studies enrolled patients (mean age early 60s, approximately 50% women) with clinically and radiographically evaluated knee OA of mostly moderate severity (baseline WOMAC scores about 50).1,2 Investigators in the first RCT injected PRP once in one subgroup and twice in another subgroup, compared with a single injection of saline in a third subgroup.1 They gave 3 weekly injections of PRP or saline in the second RCT.2
The third study enrolled mainly patients with early osteoarthritis (mean age early 50s, slightly more women). Investigators injected PRP 3 times in one subgroup and once (plus 2 saline injections) in another, compared with 3 saline injections, and evaluated patients at baseline and 6 months.3
PRP vs HA. Nine RCTs compared PRP with HA injections. Six studies (673 patients) found no significant difference; 3 studies (376 patients) found that PRP improved standardized knee assessment scores by 35% to 40% at 24-48 weeks.7,8,10 All studies enrolled patients (mean age early 60s, approximately 50% women) with clinically and radiographically evaluated knee OA of mostly moderate severity. In 7 RCTs, 4-6,9-12 investigators injected PRP or HA weekly for 3 weeks, in one RCT8 they gave 4 weekly injections, and in one7they gave 2 PRP injections separated by 4 weeks.
Three RCTs used the International Knee Documentation Committee (IKDC) score, considered the most reliable standardized scoring system, which quantifies subjective symptoms (pain, stiffness, swelling, giving way), activity (climbing stairs, rising from a chair, squatting, jumping), and function pre- and postintervention.5,9,12 All 3 studies using the IKDC found no difference between PRP and HA injections. Most RCTs used the WOMAC standardized scale, scoring 5 items for pain, 2 for stiffness, and 17 for function.1,2,4,6-8.10
Risk for bias
A systematic review13 that evaluated methodologic quality of the 3 studies comparing PRP with placebo rated 21,3 at high risk of bias and one2 at moderate risk. Another meta-analysis14 performed a quality assessment including 4 of the 9 RCTs,8-10,12 comparing PRP with HA and concluded that 3 had a high risk of bias; the fourth RCT had a moderate risk. No independent quality assessments of the other RCTs were available.4-7,11
RECOMMENDATIONS
The American Academy of Orthopaedic Surgeons doesn’t recommend for or against PRP injections because of insufficient evidence and strongly recommends against HA injections based on multiple RCTs of moderate quality that found no difference between HA and placebo.15
1. Patel S, Dhillon MS, Aggarwal S, et al. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41:356-364.
2. Smith PA. Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee arthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med. 2016;44:884-891.
3. Gorelli G, Gormelli CA, Ataoglu B, et al. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2015;25:958-965.
4. Cole BJ, Karas V, Hussey K, et al. Hyaluronic acid versus platelet-rich plasma: a prospective double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med. 2016;45:339-346.
5. Filardo G, Di Matteo B, Di Martino A, et al. Platelet-rich intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015;43:1575-1582.
6. Sanchez M, Fiz N, Azofra J, et al. A randomized clinical trial evaluating plasma rich in growth factors (PGRF-endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy: J Arth and Related Surg. 2012;28:1070-1078.
7. Raeissadat SA, Rayegani SM, Hassanabadi H, et al. Knee osteoarthritis injection choices: platelet-rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights: Arth Musc Dis. 2015;8:1-8.
8. Cerza F, Carni S, Carcangiu A, et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40:2822-2827.
9. Filardo G, Kon E, Di Martino B, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskeletal Disorders. 2012;13:229-236.
10. Vaquerizo V, Plasencia MA, Arribas I, et al. Comparison of intra-articular injections of plasma rich in growth factors (PGRF-endoret) versus durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy: J Arth and Related Surg. 2013;29:1635-1643.
11. Montanez-Heredia E, Irizar S, Huertas PJ, et al. Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritis knee pain: a randomized clinical trial in the context of the Spanish national health care system. Intl J Molec Sci. 2016;17:1064-1077.
12. Li M, Zhang C, Ai Z, et al. Therapeutic effectiveness of intra-knee articular injections of platelet-rich plasma on knee articular cartilage degeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 25:1192-11966. (Article published in Chinese with abstract in English.)
13. Shen L, Yuan T, Chen S, et al. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Ortho Surg Res. 2017;12:16.
14. Laudy ABM, Bakker EWP, Rekers M, et al. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015;49:657-672.
15. American Academy of Orthopaedic Surgeons. Clinical practice guideline on the treatment of osteoarthritis of the knee, 2nd ed. www.aaos.org/cc_files/aaosorg/research/guidelines/treatmentofosteoarthritisofthekneeguideline.pdf. Published May 2013. Accessed February 22, 2019.
1. Patel S, Dhillon MS, Aggarwal S, et al. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41:356-364.
2. Smith PA. Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee arthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med. 2016;44:884-891.
3. Gorelli G, Gormelli CA, Ataoglu B, et al. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2015;25:958-965.
4. Cole BJ, Karas V, Hussey K, et al. Hyaluronic acid versus platelet-rich plasma: a prospective double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med. 2016;45:339-346.
5. Filardo G, Di Matteo B, Di Martino A, et al. Platelet-rich intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015;43:1575-1582.
6. Sanchez M, Fiz N, Azofra J, et al. A randomized clinical trial evaluating plasma rich in growth factors (PGRF-endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy: J Arth and Related Surg. 2012;28:1070-1078.
7. Raeissadat SA, Rayegani SM, Hassanabadi H, et al. Knee osteoarthritis injection choices: platelet-rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights: Arth Musc Dis. 2015;8:1-8.
8. Cerza F, Carni S, Carcangiu A, et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40:2822-2827.
9. Filardo G, Kon E, Di Martino B, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskeletal Disorders. 2012;13:229-236.
10. Vaquerizo V, Plasencia MA, Arribas I, et al. Comparison of intra-articular injections of plasma rich in growth factors (PGRF-endoret) versus durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy: J Arth and Related Surg. 2013;29:1635-1643.
11. Montanez-Heredia E, Irizar S, Huertas PJ, et al. Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritis knee pain: a randomized clinical trial in the context of the Spanish national health care system. Intl J Molec Sci. 2016;17:1064-1077.
12. Li M, Zhang C, Ai Z, et al. Therapeutic effectiveness of intra-knee articular injections of platelet-rich plasma on knee articular cartilage degeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 25:1192-11966. (Article published in Chinese with abstract in English.)
13. Shen L, Yuan T, Chen S, et al. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Ortho Surg Res. 2017;12:16.
14. Laudy ABM, Bakker EWP, Rekers M, et al. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015;49:657-672.
15. American Academy of Orthopaedic Surgeons. Clinical practice guideline on the treatment of osteoarthritis of the knee, 2nd ed. www.aaos.org/cc_files/aaosorg/research/guidelines/treatmentofosteoarthritisofthekneeguideline.pdf. Published May 2013. Accessed February 22, 2019.
EVIDENCE-BASED ANSWER:
Probably not, based on the balance of evidence. While low-quality evidence may suggest potential benefit, the balance of evidence suggests it is no better than placebo.
Compared with saline placebo, platelet-rich plasma (PRP) injections may improve standardized scores for knee osteoarthritis (OA) pain, function, and stiffness by 24% to 70% for periods of 6 to 52 weeks in patients with early to moderate OA (strength of recommendation [SOR]: B, small randomized controlled trials [RCTs] with methodologic flaws).
Compared with hyaluronic acid (HA), PRP probably improves scores by a similar amount for periods of 8 to 52 weeks (SOR: B, multiple RCTs with conflicting results favoring no difference). However, since HA alone likely doesn’t improve scores more than placebo (SOR: B, RCTs of moderate quality), if both HA and PRP are about the same, then both are not better than placebo.
