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Is platelet-rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta-analysis of level 1 and 2 randomized controlled trials

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Abstract

Introduction

The purpose of this study was to perform a systematic review and meta-analysis comparing intra-articular knee injection of PRP and hyaluronic acid and investigate clinical outcomes and pain at both 6 and 12 months.

Methods

A systematic review of Medline, Embase, Scopus, and Google Scholar was performed in the English and German literature reporting on intra-articular knee injections for knee osteoarthritis. All level 1 and 2 studies with a minimum of 6-month follow-up in patients with knee osteoarthritis from 2010 to 2019 were included. Clinical outcome was assessed by WOMAC and IKDC scores and pain by VAS and WOMAC pain scores. Subgroup analysis for autologous platelet-rich plasma (ACP) was performed. Publication bias and risk of bias were assessed using the Cochrane Collaboration’s tools. The GRADE system was used to assess the quality of the body of evidence. Heterogeneity was assessed using χ2 and I2 statistics.

Results

Twelve studies (1,248 cases; 636 PRP, 612 HA) met the eligibility criteria. The pooled estimate demonstrated non-significant differences between PRP and HA for clinical outcomes at 6 months (p = 0.069) and at 12 months (p = 0.188). However, the pooled estimate for pain did demonstrate significant differences in favour of PRP at 6 months (p = 0.001) and 12 months (p = 0.001). For the ACP subgroup (249 cases), the pooled estimate for these studies demonstrated significant differences in favour of PRP (p < 0.0001) at 6 months.

Conclusion

The results of this systematic review and meta-analysis suggest that PRP is superior to HA for symptomatic knee pain at 6 and 12 months. ACP appears to be clearly superior over HA for pain at both 6 and 12 months. There were no advantages of PRP over HA for clinical outcomes at both 6 and 12 months.

Level of evidence

Level 2; systematic review and meta-analysis.

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References

  1. Bannuru R, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE (2015) Comparative effectiveness of pharmacological interventions for knee osteoarthritis. A systematic review and network meta-analysis. Ann Intern Med 162:46–54. https://doi.org/10.7326/m14-1231

    Article  PubMed  Google Scholar 

  2. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M et al (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic review for the global burden of disease study 2010. Lancet 380(9859):2163–2196. https://doi.org/10.1016/S0140-6736(12)61729-2

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cook CS, Smith PA (2018) Clinical update: why PRP should be your first choice for injection therapy for the knee. Curr Rev Musculoskelet Med 11:583–592. https://doi.org/10.1007/s12178-018-9524-x

    Article  PubMed  PubMed Central  Google Scholar 

  4. Vannabouthang C, Bhandari M, Bedi A, Khanna V, Yung P, Shetty V, Khan M (2018) Nonoperative treatment for knee osteoarthritis: an evaluation of treatment characteristics and the intra-articular placebo effect. A syst rev. JBJS Rev 6(7):e5. https://doi.org/10.2106/JBJS.RVW.17.00167

    Article  Google Scholar 

  5. Levy D, Petersen K, Scalley Vaught M, Christian D, Cole B (2018) Injections for knee osteoarthritis: corticosteroids, Viscosupplementation, platelet-rich plasma, and autologous stem cells. Arthroscopy 34:1730–1743. https://doi.org/10.1016/j.arthro.2018.02.022

    Article  PubMed  Google Scholar 

  6. Matzkin EG, Curry EJ, Kong Q, Rogers MJ, Henry M, Smith EL (2017) Efficacy and treatment response of intra-articular corticosteroid injections in patients with symptomatic knee osteoarthritis. J Am Acad Orthop Surg 25(10):703–714. https://doi.org/10.5435/JAAOS-D-16-00541

    Article  PubMed  Google Scholar 

  7. Jüni P, Hari R, Rutjes AW, Fischer R, Silletta MG, Reichenbach S, da Costa BR (2015) Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev (10): CD005328. doi: 10.1002/14651858.CD005328.pub3

  8. O’Hanlon CE, Newberry SJ, Booth M, Grant S, Motala A, Maglione MA, FitzGerald JD, Shekelle PG (2016) Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews. Syst Rev 5(1):186. https://doi.org/10.1186/s13643-016-0363-9

    Article  PubMed  PubMed Central  Google Scholar 

  9. Xing D, Wang B, Liu Q, Ke Y, Xu Y, Li Z, Lin J (2016) Intra-articular hyaluronic acid in treating knee osteoarthritis: a prisma-compliant systematic review of overlapping meta-analysis. Sci Rep 6:32790. https://doi.org/10.1038/srep32790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S (2012) Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med 157(3):180–191. https://doi.org/10.7326/0003-4819-157-3-201208070-00473

    Article  PubMed  Google Scholar 

  11. Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH (2019) Intra-articular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: a randomized, double-blind, triple-parallel, placebo-controlled clinical trial. Arthroscopy 35(1):106–117. https://doi.org/10.1016/j.arthro.2018.06.035

    Article  PubMed  Google Scholar 

  12. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, Fortier LA (2014) The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 42:35–41. https://doi.org/10.1177/0363546513507766

    Article  PubMed  Google Scholar 

  13. Dai WL, Ag Zhou, Zhang H, Zhang J (2017) Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Arthroscopy 33(3):659–670. https://doi.org/10.1016/j.arthro.2016.09.024

    Article  PubMed  Google Scholar 

  14. Shen L, Yuan T, Chen S, Xie X, Zhang C (2017) 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 clinical trials. J Orthop Surg Res 12:16. https://doi.org/10.1186/s13018-017-0521-3

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cerza F, Carni S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, De Biasi G, Ciuffreda M (2012) Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med 40(12):2822–2827. https://doi.org/10.1177/0363546512461902

    Article  PubMed  Google Scholar 

  16. Duymus TM, Mutlu S, Dernek B, Komur B, Aydogmus S, Kesiktas FN (2017) Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee Surg Sports Traumatol Arthrosc 25(2):485–492. https://doi.org/10.1007/s00167-016-4110-5

    Article  PubMed  Google Scholar 

  17. Görmeli G, Görmeli CA, Ataoglu B, Çolak C, Aslantürk O, Ertem K (2017) 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 25(3):958–965. https://doi.org/10.1007/s00167-015-3705-6

    Article  PubMed  Google Scholar 

  18. Lana JFSD, Weglein A, Sampson SE, Vicente EF, Huber SC, Souza CV, Ambach MA, Vincent H, Urban-Paffaro A, Onodera CM, Annichino-Bizzacchi JM, Santana MH, Belangero WD (2016) Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee. J Stem Cells Regen Med 12(2):69–78

    PubMed  PubMed Central  Google Scholar 

  19. Montanez-Heredia E, Irızar S, Huertas PJ, Otero E, Del Valle M, Prat I, Díaz-Gallardo MS, Perán M, Marchal JA, Hernandez-Lamas Mdel C (2016). Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritic knee pain: a randomized clinical trial in the context of the Spanish National Health Care System. Int J Mol Sci 17(7): pii:E1064. DOI:10.3390/ijms17071064

  20. Paterson KL, Nicholls M, Bennell KL, Bates D (2016) Intra-articular injection of photoactivated platelet-rich plasma in patients with knee osteoarthritis: a doubleblind, randomized controlled pilot study. BMC Musculoskelet Disord 17:67. https://doi.org/10.1186/s12891-016-0920-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, Azma K (2015) Knee osteoarthritis injection choices: platelet-rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord 8:1–8. https://doi.org/10.4137/CMAMD.S17894

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sanchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A, Albillos J, Gárate R, Aguirre JJ, Padilla S, Orive G, Anitua E (2012) A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy 28(8):1070–1078. https://doi.org/10.1016/j.arthro.2012.05.011

    Article  PubMed  Google Scholar 

  23. Le ADK, Enweze L, DeBaun MR, Dragoo JL (2019) Platelet-rich plasma. Clin Sports Med 38(1):17–44. https://doi.org/10.1016/j.csm.2018.08.001

    Article  PubMed  Google Scholar 

  24. Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA (2017) 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 45(2):339–346. https://doi.org/10.1177/0363546516665809

    Article  PubMed  Google Scholar 

  25. Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A, Kon E, Filardo G (2019) Platelet-rich plasma versus hyaluronic acid injections for the treatment of knee osteoarthritis: results at 5 years of a double-blind, randomized controlled trial. Am J Sports Med 47(2):347–354. https://doi.org/10.1177/0363546518814532

    Article  PubMed  Google Scholar 

  26. Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E (2015) Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med 43(7):1575–1582. https://doi.org/10.1177/0363546515582027

    Article  PubMed  Google Scholar 

  27. Filardo G, Kon E, Di Martino A, Merli ML, Cenacchi A, Fornasari PM, Marcacci M (2012) Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord 13:229. https://doi.org/10.1186/1471-2474-13-229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions. Version 5.1.9 [updated March 2011]. The Cochrane Collaboration

  29. Moher D, Liberati A, Tetzlaff J, Altman DG (2010) Preferred reporting items for systematic reviews and meta-analysis: the PRISMA statement. Int J Surg 8(5):336–341. https://doi.org/10.1016/j.ijsu.2010.02.007

    Article  PubMed  Google Scholar 

  30. Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA (2009) Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 37(11):2259–2272. https://doi.org/10.1177/0363546509349921

    Article  PubMed  Google Scholar 

  31. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13. https://doi.org/10.1186/1471-2288-5-13

    Article  PubMed  PubMed Central  Google Scholar 

  32. Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A (2012) Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil 91(5):411–417. https://doi.org/10.1097/PHM.0b013e3182aab72

    Article  PubMed  Google Scholar 

  33. Vaquerizo V, Plasencia MÁ, Arribas I, Seijas R, Padilla S, Orive G, Anitua E (2013) Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy 29(10):1635–1643. https://doi.org/10.1016/j.arthro.2013.07.264

    Article  PubMed  Google Scholar 

  34. Smith PA (2016) Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis: an FDA-sanctioned, randomized, double-blind placebo-controlled clinical trial. Am J Sports Med 44(4):884–891. https://doi.org/10.1177/0363546515624678

    Article  PubMed  Google Scholar 

  35. Kennedy MI, Whitney K, Evans T, LaPrade RF (2018) Platelet-rich plasma and cartilage repair. Curr Rev Musculoskelet Med 11(4):573–582. https://doi.org/10.1007/s12178-018-9516-x

    Article  PubMed  PubMed Central  Google Scholar 

  36. Van Buul GM, Koevoet WL, Kops N, Bos PK, Verhaar JA, Weinans H, Bernsen MR, van Osch GJ (2011) Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am J Sports Med 39(11):2362–2370. https://doi.org/10.1177/0363546511419278

    Article  PubMed  Google Scholar 

  37. Daheshia M, Yao JQ (2008) The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J Rheumatol 35:2306–2312

    Article  CAS  PubMed  Google Scholar 

  38. Boswell SG, Cole BJ, Sundman EA, Karas V, Fortier LA (2012) Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy 28:429–439. https://doi.org/10.1016/j.arthro.2011.10.018

    Article  PubMed  Google Scholar 

  39. Amin I, Gellhorn AC (2019) Platelet-rich plasma use in musculoskeletal disorders: are the factors important in standardization well understood? Phys Med Rehabili Clin N Am 30(2):439–449. https://doi.org/10.1016/j.pmr.2018.12.005

    Article  Google Scholar 

  40. Chahla J, Cinque ME, Piuzzi NS, Mannava S, Geeslin AG, Murray IR, Dornan GJ, Muschler GF, LaPrade RF (2017) A call for standardization in platelet-rich plasma preparation protocols and composition reporting: a systematic review of the clinical orthopaedic literature. J Bone Jt Surg Am 99(20):1769–1779. https://doi.org/10.2106/JBJS.16.01374

    Article  Google Scholar 

  41. Rossi LA, Murray IR, Chu CR, Muschler GF, Rodeo SA, Piuzzi NS (2019) Classification systems for platelet-rich plasma. Boner Jt J 8(5):891–896. https://doi.org/10.1302/0301-620x.101b8.bjj-2019-0037

    Article  Google Scholar 

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Erik Hohmann

  2. Department of Orthopaedic Surgery and Sports Medicine, Valiant Clinic/Houston Methodist Group, Dubai, United Arab Emirates

    Erik Hohmann

  3. Department of Orthopaedic Surgery, Royal Brisbane Hospital, Herston, Australia

    Kevin Tetsworth

  4. Department of Surgery, School of Medicine, University of Queensland, Brisbane, Australia

    Kevin Tetsworth

  5. Queensland University of Technology, Brisbane, Australia

    Kevin Tetsworth

  6. Orthopaedic Research Centre of Australia, Brisbane, Australia

    Kevin Tetsworth & Vaida Glatt

  7. University of Texas Health Science Center, San Antonio, TX, USA

    Vaida Glatt

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  1. Erik Hohmann
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Correspondence to Erik Hohmann.

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Hohmann, E., Tetsworth, K. & Glatt, V. Is platelet-rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta-analysis of level 1 and 2 randomized controlled trials. Eur J Orthop Surg Traumatol 30, 955–967 (2020). https://doi.org/10.1007/s00590-020-02623-4

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