Skip to main content
Log in

Platelet-Rich Plasma for Knee Osteoarthritis: What Does the Evidence Say?

  • Leading Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

The utilization of platelet-rich-plasma as a therapeutic intervention for knee osteoarthritis has gained immense attention since 2008. The increase in the number of scientific publications dedicated to this area can be attributed to the majority of favorable results reported in clinical trials and basic science studies. However, despite the growing evidence, the use of platelet-rich plasma in clinical practice still poses controversial aspects. The potential mechanisms of action described for platelet-rich-plasma so far indicate that it could serve as a disease-modifying drug, acting to counteract important aspects of knee osteoarthritis pathophysiology (cartilage breakdown, inflammation, and bone remodeling). Nevertheless, its efficacy in slowing down the progression of knee osteoarthritis remains unproven. While inconsistencies have been noted, the majority of controlled clinical trials and meta-analyses advocate for the utilization of platelet-rich-plasma in treating knee osteoarthritis, as it has demonstrated greater efficacy than hyaluronic acid and placebo, with a follow-up of at least 1 year. Despite advancements made in certain areas, significant diversity persists regarding the formulations used, therapeutic regimen, extended follow-up periods, patient selection, and assessment of clinically relevant outcomes. Consequently, the leading clinical practice guidelines do not recommend its use. In light of the emerging evidence, this narrative review aims to provide an objective evaluation of the recent available scientific literature (last 5 years) focused on randomized clinical trials and meta-analyses to present a current overview of the topic.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Johnson VL, Hunter DJ. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 2014;28(1):5–15.

    PubMed  Google Scholar 

  2. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745–59.

    CAS  PubMed  Google Scholar 

  3. Bijlsma JWJ, Berenbaum F, Lafeber FPJG. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377(9783):2115–26.

    PubMed  Google Scholar 

  4. Vaishya R, Sathish Kumar S, Vaish A, Babu YSS. Effectiveness of the guidelines for the non-operative management of knee osteoarthritis. Arch Bone Jt Surg. 2021;9(4):472–4.

    PubMed  PubMed Central  Google Scholar 

  5. Uivaraseanu B, Vesa C, Tit D, Abid A, Maghiar O, Maghiar T, et al. Therapeutic approaches in the management of knee osteoarthritis (Review). Exp Ther Med. 2022;23(5):328.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartil. 2014;22(3):363–88.

    CAS  Google Scholar 

  7. Gigante A, Callegari L. The role of intra-articular hyaluronan (Sinovial®) in the treatment of osteoarthritis. Rheumatol Int. 2011;31(4):427–44.

    PubMed  Google Scholar 

  8. Lapane KL, Yang S, Driban JB, Liu S-H, Dubé CE, McAlindon TE, et al. Effects of prescription nonsteroidal antiinflammatory drugs on symptoms and disease progression among patients with knee osteoarthritis. Arthritis Rheumatol. 2015;67(3):724–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Conrozier T. How to treat osteoarthritis in obese patients? Curr Rheumatol Rev. 2020;16(2):99–104.

    PubMed  Google Scholar 

  10. Bennell KL, Hunter DJ, Paterson KL. Platelet-rich plasma for the management of hip and knee osteoarthritis. Curr Rheumatol Rep. 2017;19(5):24.

    PubMed  Google Scholar 

  11. Zhang H, Wang C, Li H, Huang Y, Li Z. Intra-articular platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis. Drug Des Devel Ther. 2018;12:445–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Shen L, Yuan T, Chen S, Xie X, Zhang C. 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 Orthop Surg Res. 2017;12(1):16.

    PubMed  PubMed Central  Google Scholar 

  13. Rezuş E, Burlui A, Cardoneanu A, Macovei LA, Tamba BI, Rezuş C. From pathogenesis to therapy in knee osteoarthritis: bench-to-bedside. Int J Mol Sci. 2021;22(5):2697.

    PubMed  PubMed Central  Google Scholar 

  14. Phillips M, Bhandari M, Grant J, Bedi A, Trojian T, Johnson A, et al. A systematic review of current clinical practice guidelines on intra-articular hyaluronic acid, corticosteroid, and platelet-rich plasma injection for knee osteoarthritis:aAn international perspective. Orthop J Sport Med. 2021;9(8):232596712110302.

    Google Scholar 

  15. Brophy RH, Fillingham YA. AAOS clinical practice guideline summary: management of osteoarthritis of the knee (nonarthroplasty), third edition. J Am Acad Orthop Surg. 2022;30(9):e721–9.

    PubMed  Google Scholar 

  16. American Academy of Orthopaedic Surgeons. Management of osteoarthritis of the knee (non-arthroplasty) evidence-based clinical practice guideline. August 2021. https://www.aaos.org/oak3cpg.

  17. Arnoczky SP, Shebani-Rad S. The basic science of platelet-rich plasma (PRP). Sports Med Arthrosc. 2013;21(4):180–5.

    PubMed  Google Scholar 

  18. Anitua E, Andia I, Ardanza B, Nurden P, Nurden A. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004;91(01):4–15.

    CAS  PubMed  Google Scholar 

  19. Halpern BC, Chaudhury S, Rodeo SA. The role of platelet-rich plasma in inducing musculoskeletal tissue healing. HSS J. 2012;8(2):137–45.

    PubMed  PubMed Central  Google Scholar 

  20. Yadav S, Storrie B. The cellular basis of platelet secretion: emerging structure/function relationships. Platelets. 2017;28(2):108–18.

    CAS  PubMed  Google Scholar 

  21. Sharda A, Flaumenhaft R. The life cycle of platelet granules. F1000Research. 2018;7:236.

    PubMed  PubMed Central  Google Scholar 

  22. Blair P, Flaumenhaft R. Platelet α-granules: basic biology and clinical correlates. Blood Rev. 2009;23(4):177–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Maynard DM, Heijnen HFG, Gahl WA, Gunay-Aygun M. The α-granule proteome: novel proteins in normal and ghost granules in gray platelet syndrome. J Thromb Haemost. 2010;8(8):1786–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Smyth NA, Murawski CD, Fortier LA, Cole BJ, Kennedy JG. Platelet-rich plasma in the pathologic processes of cartilage: review of basic science evidence. Arthroscopy. 2013;29(8):1399–409.

    PubMed  Google Scholar 

  25. Woodell-May J, Steckbeck K, King W. Potential mechanism of action of current point-of-care autologous therapy treatments for osteoarthritis of the knee: a narrative review. Int J Mol Sci. 2021;22(5):2726.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Dernek B, Kesiktas FN, Duymus TM, Aydin T, Isiksacan N, Diracoglu D, et al. Effect of platelet concentration on clinical improvement in treatment of early stage-knee osteoarthritis with platelet-rich plasma concentrations. J Phys Ther Sci. 2017;29(5):896–901.

    PubMed  PubMed Central  Google Scholar 

  27. Kikuchi N, Yoshioka T, Arai N, Sugaya H, Hyodo K, Taniguchi Y, et al. A retrospective analysis of clinical outcome and predictive factors for responders with knee osteoarthritis to a single injection of leukocyte-poor platelet-rich plasma. J Clin Med. 2021;10(21):5121.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Nguyen PA, Pham TAV. Effects of platelet-rich plasma on human gingival fibroblast proliferation and migration in vitro. J Appl Oral Sci. 2018;10(26):1–9.

    Google Scholar 

  29. Vahabi S, Yadegari Z, Mohammad-Rahimi H. Comparison of the effect of activated or non-activated PRP in various concentrations on osteoblast and fibroblast cell line proliferation. Cell Tissue Bank. 2017;18(3):347–53.

    CAS  PubMed  Google Scholar 

  30. Naja M, Fernandez De Grado G, Favreau H, Scipioni D, Benkirane-Jessel N, Musset A-MM, et al. Comparative effectiveness of nonsurgical interventions in the treatment of patients with knee osteoarthritis: a PRISMA-compliant systematic review and network meta-analysis. Medicine (Baltimore). 2021;100(49):e28067.

    CAS  PubMed  Google Scholar 

  31. Anil U, Markus DH, Hurley ET, Manjunath AK, Alaia MJ, Campbell KA, et al. The efficacy of intra-articular injections in the treatment of knee osteoarthritis: a network meta-analysis of randomized controlled trials. Knee. 2021;32:173–82.

    PubMed  Google Scholar 

  32. Abbas A, Du JT, Dhotar HS. The effect of leukocyte concentration on platelet-rich plasma injections for knee osteoarthritis. J Bone Jt Surg. 2022;104(6):559–70.

    Google Scholar 

  33. Martino MM, Briquez PS, Güç E, Tortelli F, Kilarski WW, Metzger S, et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science. 2014;343(6173):885–8.

    CAS  PubMed  Google Scholar 

  34. Anitua E, Prado R, Azkargorta M, Rodriguez-Suárez E, Iloro I, Casado-Vela J, et al. High-throughput proteomic characterization of plasma rich in growth factors (PRGF-Endoret)-derived fibrin clot interactome. J Tissue Eng Regen Med. 2015;9(11):E1-12.

    CAS  PubMed  Google Scholar 

  35. Sánchez M, Anitua E, Delgado D, Sanchez P, Prado R, Goiriena JJ, et al. A new strategy to tackle severe knee osteoarthritis: combination of intra-articular and intraosseous injections of Platelet Rich Plasma. Expert Opin Biol Ther. 2016;16(5):627–43.

    PubMed  Google Scholar 

  36. Ngarmukos S, Tanavalee C, Amarase C, Phakham S, Mingsiritham W, Reantragoon R, et al. Two or four injections of platelet-rich plasma for osteoarthritic knee did not change synovial biomarkers but similarly improved clinical outcomes. Sci Rep. 2021;11(1):23603.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lin W, Xie L, Zhou L, Zheng J, Zhai W, Lin D. Effects of platelet-rich plasma on subchondral bone marrow edema and biomarkers in synovial fluid of knee osteoarthritis. Knee. 2023;42:161–9.

    PubMed  Google Scholar 

  38. Khatab S, van Buul GM, Kops N, Bastiaansen-Jenniskens YM, Bos PK, Verhaar JA, et al. Intra-articular injections of platelet-rich plasma releasate reduce pain and synovial inflammation in a mouse model of osteoarthritis. Am J Sports Med. 2018;46(4):977–86.

    PubMed  Google Scholar 

  39. Sakata R, McNary SM, Miyatake K, Lee CA, Van den Bogaerde JM, Marder RA, et al. Stimulation of the superficial zone protein and lubrication in the articular cartilage by human platelet-rich plasma. Am J Sports Med. 2015;43(6):1467–73.

    PubMed  PubMed Central  Google Scholar 

  40. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014;42(1):35–41.

    PubMed  Google Scholar 

  41. Boffa A, Poggi A, Romandini I, Asunis E, Pizzuti V, Di Martino A, et al. Does bone marrow edema influence the clinical results of intra-articular platelet-rich plasma injections for knee osteoarthritis? J Clin Med. 2022;11(15):4414.

    PubMed  PubMed Central  Google Scholar 

  42. Tudorachi NB, Totu EE, Fifere A, Ardeleanu V, Mocanu V, Mircea C, et al. The implication of reactive oxygen species and antioxidants in knee osteoarthritis. Antioxidants. 2021;10(6):985.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Yang J, Lu Y, Guo A. Platelet-rich plasma protects rat chondrocytes from interleukin-1β-induced apoptosis. Mol Med Rep. 2016;14(5):4075–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Carmona JU, Ríos DL, López C, Álvarez ME, Pérez JE, Bohórquez ME. In vitro effects of platelet-rich gel supernatants on histology and chondrocyte apoptosis scores, hyaluronan release and gene expression of equine cartilage explants challenged with lipopolysaccharide. BMC Vet Res. 2016;12(1):135.

  45. Liu X, Wang L, Ma C, Wang G, Zhang Y, Sun S. Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway. J Orthop Surg Res. 2019;14(1):470.

  46. Braun HJ, Kim HJ, Chu CR, Dragoo JL. The effect of platelet-rich plasma formulations and blood products on human synoviocytes. Am J Sports Med. 2014;42(5):1204–10.

    PubMed  PubMed Central  Google Scholar 

  47. Simental-Mendíal M, Vilchez-Cavazos F, García-Garza R, Lara-Arias J, Montes-De-Oca-Luna R, Said-Fernándezi S, et al. The matrix synthesis and anti-inflammatory effect of autologous leukocyte-poor platelet rich plasma in human cartilage explants. Histol Histopathol. 2018;33:609–18.

    Google Scholar 

  48. Asjid R, Faisal T, Qamar K, Khan SA, Khalil A, Zia MS. Platelet-rich plasma-induced inhibition of chondrocyte apoptosis directly affects cartilage thickness in osteoarthritis. Cureus. 2019;11(11):e650.

  49. Akeda K, An HS, Okuma M, Attawia M, Miyamoto K, Thonar EJMA, et al. Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthritis Cartil. 2006;14(12):1272–80.

    CAS  Google Scholar 

  50. Jeyakumar V, Niculescu-Morzsa E, Bauer C, Lacza Z, Nehrer S. Platelet-rich plasma supports proliferation and redifferentiation of chondrocytes during in vitro expansion. Front Bioeng Biotechnol. 2017;6(5):75.

    Google Scholar 

  51. Moussa M, Lajeunesse D, Hilal G, El Atat O, Haykal G, Serhal R, et al. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage. Exp Cell Res. 2017;352(1):146–56.

    CAS  PubMed  Google Scholar 

  52. Chen WH, Lo WC, Hsu WC, Wei HJ, Liu HY, Lee CH, et al. Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials. 2014;35(36):9599–607.

    CAS  PubMed  Google Scholar 

  53. Wu CC, Chen WH, Zao B, Lai PL, Lin TC, Lo HY, et al. Regenerative potentials of platelet-rich plasma enhanced by collagen in retrieving pro-inflammatory cytokine-inhibited chondrogenesis. Biomaterials. 2011;32(25):5847–54.

    CAS  PubMed  Google Scholar 

  54. Wang CC, Lee C-HH, Peng YJ, Salter DM, Lee HS. Platelet-rich plasma attenuates 30-kDa fibronectin fragment-induced chemokine and matrix metalloproteinase expression by meniscocytes and articular chondrocytes. Am J Sports Med. 2015;43(10):2481–9.

    PubMed  Google Scholar 

  55. Assirelli E, Filardo G, Mariani E, Kon E, Roffi A, Vaccaro F, et al. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2690–703.

    PubMed  Google Scholar 

  56. Mariani E, Roffi A, Cattini L, Pulsatelli L, Assirelli E, Krishnakumar GS, et al. Release kinetic of pro- and anti-inflammatory biomolecules from platelet-rich plasma and functional study on osteoarthritis synovial fibroblasts. Cytotherapy. 2020;22(7):344–53.

    CAS  PubMed  Google Scholar 

  57. Van Buul GM, Koevoet WLMM, Kops N, Bos PK, Verhaar JANN, Weinans H, et al. Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am J Sports Med. 2011;39(11):2362–70.

    PubMed  Google Scholar 

  58. Yin W, Xu H, Sheng J, Xu Z, Xie X, Zhang C. Comparative evaluation of the effects of platelet-rich plasma formulations on extracellular matrix formation and the NF-κB signaling pathway in human articular chondrocytes. Mol Med Rep. 2017;15(5):2940–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Andia I, Atilano L, Maffulli N. Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211004336.

  60. Szwedowski D, Szczepanek J, Paczesny Ł, Zabrzyński J, Gagat M, Mobasheri A, et al. The effect of platelet-rich plasma on the intra-articular microenvironment in knee osteoarthritis. Int J Mol Sci. 2021;22(11):5492.

  61. Osterman C, Mccarthy MBR, Cote MP, Beitzel K, Bradley J, Polkowski G, et al. Platelet-rich plasma increases anti-inflammatory markers in a human coculture model for osteoarthritis. Am J Sports Med. 2015;43(6):1474–84.

    PubMed  Google Scholar 

  62. Ríos DL, López C, Carmona JU. Evaluation of the anti-inflammatory effects of two platelet-rich gel supernatants in an in vitro system of cartilage inflammation. Cytokine. 2015;76(2):505–13.

    PubMed  Google Scholar 

  63. Matuska A, O’Shaughnessey K, King W, Woodell-May J. Autologous solution protects bovine cartilage explants from IL-1α- and TNFα-induced cartilage degradation. J Orthop Res. 2013;31(12):1929–35.

    CAS  PubMed  Google Scholar 

  64. Kisiday JD, McIlwraith CW, Rodkey WG, Frisbie DD, Steadman JR. Effects of platelet-rich plasma composition on anabolic and catabolic activities in equine cartilage and meniscal explants. Cartilage. 2012;3(3):245–54.

    PubMed  PubMed Central  Google Scholar 

  65. Primorac D, Molnar V, Rod E, Jeleč Ž, Čukelj F, Matišić V, et al. Knee osteoarthritis: a review of pathogenesis and state-of-the-art non-operative therapeutic considerations. Genes (Basel). 2020;11(8):1–35.

    Google Scholar 

  66. Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A, et al. 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. 2019;47(2):347–54.

    PubMed  Google Scholar 

  67. Chu J, Duan W, Yu Z, Tao T, Xu J, Ma Q, et al. Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2022;30(12):4063–71.

    PubMed  Google Scholar 

  68. Nunes-Tamashiro JC, Natour J, Ramuth FM, Toffolo SR, Mendes JG, Rosenfeld A, et al. Intra-articular injection with platelet-rich plasma compared to triamcinolone hexacetonide or saline solution in knee osteoarthritis: a double blinded randomized controlled trial with one year follow-up. Clin Rehabil. 2022;36(7):900–15.

    PubMed  Google Scholar 

  69. Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH. 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. 2019;35(1):106–17.

    PubMed  Google Scholar 

  70. Lewis E, Merghani K, Robertson I, Mulford J, Prentice B, Mathew R, et al. The effectiveness of leucocyte-poor platelet-rich plasma injections on symptomatic early osteoarthritis of the knee: the PEAK randomized controlled trial. Bone Jt J. 2022;104-B(6):663–71.

    Google Scholar 

  71. Yurtbay A, Say F, Çinka H, Ersoy A. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Arch Orthop Trauma Surg. 2021;142(10):2755-68.

  72. Bennell KL, Paterson KL, Metcalf BR, Duong V, Eyles J, Kasza J, et al. Effect of intra-articular platelet-rich plasma vs placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial. JAMA. 2021;326(20):2021–30.

    CAS  PubMed  Google Scholar 

  73. Mojica ES, Markus DH, Hurley ET, Blaeser AM, Jazrawi LM, Campbell KA, et al. Estimated time to maximum medical improvement of intra-articular injections in the treatment of knee osteoarthritis: a systematic review. Arthroscopy. 2022;38(3):980-8.e4.

    PubMed  Google Scholar 

  74. Salehi R, Valizadeh L, Negahban H, Karimi M, Goharpey S, Shahali S. The Western Ontario and McMaster Universities Osteoarthritis, Lequesne Algofunctional index, Arthritis Impact Measurement Scale-short form, and Visual Analogue Scale in patients with knee osteoarthritis: responsiveness and minimal clinically important differences. Disabil Rehabil. 2022. https://doi.org/10.1080/09638288.2022.2084776.

  75. Kim J-HH, Park Y-BB, Ha C-WW, Roh YJ, Park J-GG. Adverse reactions and clinical outcomes for leukocyte-poor versus leukocyte-rich platelet-rich plasma in knee osteoarthritis: a systematic review and meta-analysis. Orthop J Sport Med. 2021;9(6):232596712110119.

    Google Scholar 

  76. Raeissadat SA, Ahangar AG, Rayegani SM, Sajjadi MM, Ebrahimpour A, Yavari P. Platelet-rich plasma-derived growth factor vs hyaluronic acid injection in the individuals with knee osteoarthritis: a one year randomized clinical trial. J Pain Res. 2020;13:1699–711.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Di Martino A, Boffa A, Andriolo L, Romandini I, Altamura SA, Cenacchi A, et al. Leukocyte-rich versus leukocyte-poor platelet-rich plasma for the treatment of knee osteoarthritis: a double-blind randomized trial. Am J Sports Med. 2022;50(3):609–17.

    PubMed  Google Scholar 

  78. Elksniņš-Finogejevs A, Vidal L, Peredistijs A. Intra-articular platelet-rich plasma vs corticosteroids in the treatment of moderate knee osteoarthritis: a single-center prospective randomized controlled study with a 1-year follow up. J Orthop Surg Res. 2020;15(1):1–10.

    Google Scholar 

  79. Huang Y, Liu X, Xu X, Liu J. Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis: a prospective randomized controlled study. Orthopade. 2019;48(3):239–47.

    PubMed  Google Scholar 

  80. Subramanyam K, Alguvelly R, Mundargi A, Khanchandani P. Single versus multi-dose intra-articular injection of platelet rich plasma in early stages of osteoarthritis of the knee: a single-blind, randomized, superiority trial. Arch Rheumatol. 2021;36(3):326–34.

    PubMed  PubMed Central  Google Scholar 

  81. Raeissadat SA, Ghazi Hosseini P, Bahrami MH, Salman Roghani R, Fathi M, Gharooee Ahangar A, et al. The comparison effects of intra-articular injection of platelet rich plasma (PRP), plasma rich in growth factor (PRGF), hyaluronic acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial. BMC Musculoskelet Disord. 2021;22(1):134.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Elksniņš-Finogejevs A, Vidal L, Peredistijs A. Intra-articular platelet-rich plasma vs corticosteroids in the treatment of moderate knee osteoarthritis: a single-center prospective randomized controlled study with a 1-year follow up. J Orthop Surg Res. 2020;15(1):257.

    PubMed  PubMed Central  Google Scholar 

  83. Buendía-López D, Medina-Quirós M, Fernández-Villacañas Marín MÁ. Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: a randomized controlled trial. J Orthop Traumatol. 2018;19(1):3.

  84. Lisi C, Perotti C, Scudeller L, Sammarchi L, Dametti F, Musella V, et al. Treatment of knee osteoarthritis: platelet-derived growth factors vs. hyaluronic acid: a randomized controlled trial. Clin Rehabil. 2018;32(3):330–9.

    PubMed  Google Scholar 

  85. Han SB, Seo IW, Shin YS. Intra-articular injections of hyaluronic acid or steroids associated with better outcomes than platelet-rich plasma, adipose mesenchymal stromal cells, or placebo in knee osteoarthritis: a network meta-analysis. Arthroscopy. 2021;37(1):292–306.

    CAS  PubMed  Google Scholar 

  86. Dai W-L, Zhou A-G, Zhang H, Zhang J. Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Arthroscopy. 2017;33(3):659-70.e1.

    PubMed  Google Scholar 

  87. Zhao D, Pan J-K, Yang W-Y, Han Y-H, Zeng L-F, Liang G-H, et al. Intra-articular injections of platelet-rich plasma, adipose mesenchymal stem cells, and bone marrow mesenchymal stem cells associated with better outcomes than hyaluronic acid and saline in knee osteoarthritis: a systematic review and network meta-analysis. Arthroscopy. 2021;37(7):2298-314.e10.

    PubMed  Google Scholar 

  88. Cao Z, Li Y, Gao F, Wu R, Dou P, Wang W, et al. Mesenchymal stem cells: a new choice for nonsurgical treatment of OA? Results from a Bayesian network meta-analysis. Biomed Res Int. 2021;2021:6663003.

  89. Nie LY, Zhao K, Ruan J, Xue J. Effectiveness of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled clinical trials. Orthop J Sport Med. 2021;9(3). https://doi.org/10.1177/2325967120973284.

  90. Chen P, Huang L, Ma Y, Zhang D, Zhang X, Zhou J, et al. Intra-articular platelet-rich plasma injection for knee osteoarthritis: a summary of meta-analyses. J Orthop Surg Res. 2019;14(1):385.

  91. Sax OC, Chen Z, Mont MA, Delanois RE. The efficacy of platelet-rich plasma for the treatment of knee osteoarthritis symptoms and structural changes: a systematic review and meta-analysis. J Arthroplasty. 2022;37(11):2282-90.e2.

    PubMed  Google Scholar 

  92. Singh H, Knapik DM, Polce EM, Eikani CK, Bjornstad AH, Gursoy S, et al. Relative efficacy of intra-articular injections in the treatment of knee osteoarthritis: a systematic review and network meta-analysis. Am J Sports Med. 2022;50(11):3140–8.

    PubMed  Google Scholar 

  93. Migliorini F, Driessen A, Quack V, Sippel N, Cooper B, Mansy YE, et al. Comparison between intra-articular infiltrations of placebo, steroids, hyaluronic and PRP for knee osteoarthritis: a Bayesian network meta-analysis. Arch Orthopaed Trauma Surg. 2021;141:1473–90.

    Google Scholar 

  94. Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP injections for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Cartilage. 2021;13(1_Suppl):364S-S375.

    PubMed  Google Scholar 

  95. Costa LAV, Lenza M, Irrgang JJ, Fu FH, Ferretti M. How does platelet-rich plasma compare clinically to other therapies in the treatment of knee osteoarthritis? A systematic review and meta-analysis. Am J Sports Med. 2022;51(4):1074-86.

  96. Hong M, Cheng C, Sun X, Yan Y, Zhang Q, Wang W, et al. Efficacy and safety of intra-articular platelet-rich plasma in osteoarthritis knee: a systematic review and meta-analysis. Biomed Res Int. 2021;2021:2191926.

  97. Dai W-L, Zhou A-G, Zhang H, Zhang J. Most effective regimen of tranexamic acid for reducing bleeding and transfusions in primary total knee arthroplasty: a meta-analysis of randomized controlled trials. J Knee Surg. 2018;31(7):654–63.

    PubMed  Google Scholar 

  98. Tang JZ, Nie MJ, Zhao JZ, Zhang GC, Zhang Q, Wang B. Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis. J Orthop Surg Res. 2020;15(1):403.

  99. Anitua E, Zalduendo MM, Prado R, Alkhraisat MH, Orive G. Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion. J Biomed Mater Res A. 2015;103(3):1011–20.

    CAS  PubMed  Google Scholar 

  100. Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. 2021;49(1):249–60.

    PubMed  Google Scholar 

  101. Kim J-H, Park Y-B, Ha C-W. Are leukocyte-poor or multiple injections of platelet-rich plasma more effective than hyaluronic acid for knee osteoarthritis? A systematic review and meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2022. https://doi.org/10.1007/s00402-022-04637-5.

  102. Vilchez-Cavazos F, Millán-Alanís JM, Blázquez-Saldaña J, Álvarez-Villalobos N, Peña-Martínez VM, Acosta-Olivo CA, et al. Comparison of the clinical effectiveness of single versus multiple injections of platelet-rich plasma in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Orthopaed J Sports Med. 2019;7:2325967119887116.

    Google Scholar 

  103. Vilchez-Cavazos F, Blázquez-Saldaña J, Gamboa-Alonso AA, Peña-Martínez VM, Acosta-Olivo CA, Sánchez-García A, et al. The use of platelet-rich plasma in studies with early knee osteoarthritis versus advanced stages of the disease: a systematic review and meta-analysis of 31 randomized clinical trials. Arch Orthop Trauma Surg. 2023;143(3):1393–408.

    PubMed  Google Scholar 

  104. McLarnon M, Heron N. Intra-articular platelet-rich plasma injections versus intra-articular corticosteroid injections for symptomatic management of knee osteoarthritis: systematic review and meta-analysis. BMC Musculoskelet Disord. 2021;22(1):550.

    PubMed  PubMed Central  Google Scholar 

  105. Zhao J, Huang H, Liang G, Zeng L, Yang W, Liu J. Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2020;21(1):224.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Milants C, Bruyère O, Kaux J-F. Responders to platelet-rich plasma in osteoarthritis: a technical analysis. Biomed Res Int. 2017;2017:7538604.

    PubMed  PubMed Central  Google Scholar 

  107. Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, et al. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015;43(7):1575–82.

    PubMed  Google Scholar 

  108. Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012;13(1):229.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Bansal H, Leon J, Pont JL, Wilson DA, Bansal A, Agarwal D, et al. Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: correct dose critical for long term clinical efficacy. Sci Rep. 2021;11(1):3971.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(10):2135–40.

    PubMed  Google Scholar 

  111. Mariani E, Canella V, Cattini L, Kon E, Marcacci M, Di Matteo B, et al. Leukocyte-rich platelet-rich plasma injections do not up-modulate intra-articular pro-inflammatory cytokines in the osteoarthritic knee. PLoS One. 2016;11(6):e0156137.

  112. Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ. Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis. Am J Sports Med. 2016;44(3):792–800.

    PubMed  Google Scholar 

  113. Trams E, Kulinski K, Kozar-Kaminska K, Pomianowski S, Kaminski R. The clinical use of platelet-rich plasma in knee disorders and surgery: a systematic review and meta-analysis. Life. 2020;10(6):94.

    PubMed  PubMed Central  Google Scholar 

  114. Ha C-W, Park Y-B, Jang JW, Kim M, Kim J-A, Park Y-G. Variability of the composition of growth factors and cytokines in platelet-rich plasma from the knee with osteoarthritis. Arthroscopy. 2019;35(10):2878-84.e1.

    PubMed  Google Scholar 

  115. Hohmann E. Editorial commentary: platelet-rich plasma or profit-rich placebo: variability of composition, concentration, preparation, and many other yet-unknown factors determine effectiveness. Arthroscopy. 2019;35(10):2885–6.

    PubMed  Google Scholar 

  116. Kuffler DP. Variables affecting the potential efficacy of PRP in providing chronic pain relief. J Pain Res. 2019;12:109–16.

    CAS  PubMed  Google Scholar 

  117. Chahla J, Cinque ME, Piuzzi NS, Mannava S, Geeslin AG, Murray IR, et al. 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. 2017;99(20):1769–79.

    Google Scholar 

  118. Pachito DV, Bagattini AM, de Almeida AM, Mendrone-Júnior A, Riera R. Technical procedures for preparation and administration of platelet-rich plasma and related products: a scoping review. Front Cell Dev Biol. 2020;11:8.

    Google Scholar 

  119. Fitzpatrick J, Bulsara MK, McCrory PR, Richardson MD, Zheng MH. Analysis of platelet-rich plasma extraction. Orthop J Sport Med. 2017;5(1):232596711667527.

    Google Scholar 

  120. Collins T, Alexander D, Barkatali B. Platelet-rich plasma: a narrative review. EFORT Open Rev. 2021;64(4):225–35.

    Google Scholar 

  121. Magalon J, Velier M, Louis ML, Mattei JC, Ollivier M, Sabatier F. Changing the paradigm in PRP characterization: letter to the editor. Am J Sports Med. 2017;45(13):NP34–5.

    PubMed  Google Scholar 

  122. Delong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. Arthroscopy. 2012;28(7):998–1009.

    PubMed  Google Scholar 

  123. Mishra A, Harmon K, Woodall J, Vieira A. Sports medicine applications of platelet rich plasma. Curr Pharm Biotechnol. 2012;13(7):1185–95.

    CAS  PubMed  Google Scholar 

  124. Lana JFSD, Purita J, Paulus C, Huber SC, Rodrigues BL, Rodrigues AA, et al. Contributions for classification of platelet rich plasma: proposal of a new classification: MARSPILL. Regen Med. 2017;12(5):565–74.

    CAS  PubMed  Google Scholar 

  125. Kon E, Di Matteo B, Delgado D, Cole BJ, Dorotei A, Dragoo JL, et al. Platelet-rich plasma for the treatment of knee osteoarthritis: an expert opinion and proposal for a novel classification and coding system. Expert Opin Biol Ther. 2020;20(12):1447–60.

    CAS  PubMed  Google Scholar 

  126. Mishra AK, Skrepnik NV, Edwards SG, Jones GL, Sampson S, Vermillion DA, et al. Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med. 2014;42(2):463–71.

    PubMed  Google Scholar 

  127. Guler O, Mutlu S, Isyar M, Seker A, Kayaalp ME, Mahirogullari M. Comparison of short-term results of intraarticular platelet-rich plasma (PRP) and hyaluronic acid treatments in early-stage gonarthrosis patients. Eur J Orthop Surg Traumatol. 2015;25(3):509–13.

    CAS  PubMed  Google Scholar 

  128. Wang Y-C, Lee C-L, Chen Y-J, Tien Y-C, Lin S-Y, Chen C-H, et al. Comparing the efficacy of intra-articular single platelet-rich plasma (PRP) versus novel crosslinked hyaluronic acid for early-stage knee osteoarthritis: a prospective, double-blind, randomized controlled trial. Medicina (B Aires). 2022;58(8):1028.

    Google Scholar 

  129. Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy. 2016;32(3):495–505.

    PubMed  Google Scholar 

  130. Nicholls M, Shaw P, Niazi F, Bhandari M, Bedi A. The impact of excluding patients with end-stage knee disease in intra-articular hyaluronic acid trials: a systematic review and meta-analysis. Adv Ther. 2019;36(1):147–61.

    CAS  PubMed  Google Scholar 

  131. Elik H, Doğu B, Yılmaz F, Begoğlu FA, Kuran B. The efficiency of platelet-rich plasma treatment in patients with knee osteoarthritis. J Back Musculoskelet Rehabil. 2020;33(1):127–38.

    PubMed  Google Scholar 

  132. Anzillotti G, Conte P, Matteo BDI, Bertolino EM, Marcacci M, Kon E. Injection of biologic agents for treating severe knee osteoarthritis: is there a chance for a good outcome? A systematic review of clinical evidence. Eur Rev Med Pharmacol Sci. 2022;26(15):5447–59.

    CAS  PubMed  Google Scholar 

  133. Kemmochi M. Consecutive injections of leukocyte-rich platelet-rich plasma are effective in not only mild but also severe knee degeneration. J Orthop. 2022;1(29):31–7.

    Google Scholar 

  134. Sánchez M, Jorquera C, Sánchez P, Beitia M, García-Cano B, Guadilla J, et al. Platelet-rich plasma injections delay the need for knee arthroplasty: a retrospective study and survival analysis. Int Orthop. 2021;45(2):401–10.

    PubMed  Google Scholar 

  135. Muthuri SG, Hui M, Doherty M, Zhang W. What if we prevent obesity? Risk reduction in knee osteoarthritis estimated through a meta-analysis of observational studies. Arthritis Care Res (Hoboken). 2011;63(7):982–90.

    PubMed  Google Scholar 

  136. Cole BJ, Karas V, Hussey K, Merkow DB, Pilz K, Fortier LA. 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. 2017;45(2):339–46.

    PubMed  Google Scholar 

  137. Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A, et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):472–9.

    PubMed  Google Scholar 

  138. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41:356–64.

    PubMed  Google Scholar 

  139. Kanthawang T, Bodden J, Joseph GB, Lane NE, Nevitt M, McCulloch CE, et al. Obese and overweight individuals have greater knee synovial inflammation and associated structural and cartilage compositional degeneration: data from the osteoarthritis initiative. Skelet Radiol. 2021;50(1):217–29.

    Google Scholar 

  140. Batushansky A, Zhu S, Komaravolu RK, South S, Mehta-D’souza P, Griffin TM. Fundamentals of OAL: an initiative of osteoarthritis and cartilage. Obesity and metabolic factors in OA. Osteoarthritis Cartil. 2022;30(4):501–15.

    CAS  Google Scholar 

  141. Calvet J, García-Manrique M, Berenguer-Llergo A, Orellana C, Cirera SG, Llop M, et al. Metabolic and inflammatory profiles define phenotypes with clinical relevance in female knee osteoarthritis patients with joint effusion. Rheumatology (Oxford). 2023. https://doi.org/10.1093/rheumatology/kead135.

  142. Khoshbin A, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilvie-Harris D, et al. The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthroscopy. 2013;29(12):2037–48.

    PubMed  Google Scholar 

  143. Xing D, Wang B, Zhang W, Yang Z, Hou Y, Chen Y, et al. Intra-articular platelet-rich plasma injections for knee osteoarthritis: an overview of systematic reviews and risk of bias considerations. Int J Rheum Dos. 2017;2:1612–30.

    Google Scholar 

  144. Pourcho AM, Smith J, Wisniewski SJ, Sellon JL. Intraarticular platelet-rich plasma injection in the treatment of knee osteoarthritis: review and recommendations. Am J Phys Med Rehabil. 2014;93(11):S108–21.

    PubMed  Google Scholar 

  145. Halpern B, Chaudhury S, Rodeo SA, Hayter C, Bogner E, Potter HG, et al. Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis. Clin J Sport Med. 2013;23(3):238–9.

    PubMed  Google Scholar 

  146. Raeissadat SA, Ghorbani E, Taheri MS, Soleimani R, Rayegani SM, Babaee M, et al. MRI changes after platelet rich plasma injection in knee osteoarthritis (randomized clinical trial). J Pain Res. 2020;13:65–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. De Girolamo L, Laver L. ESSKA European ORBIT consensus. ESSKA. 2022. Available from: https://cdn.ymaws.com/www.esska.org/resource/resmgr/docs/consensus_projects/orbit_consensus_complete2022.pdf.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carlos A. Acosta-Olivo.

Ethics declarations

Funding

No funding was received for the preparation of this article.

Conflict of interest

Mario Simental-Mendía, Daniela Ortega-Mata, and Carlos Acosta-Olivo have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Author contributions

All authors had full access to the data in the study and take responsibility for the information. MS-M: design and conception of the research idea, literature search, design of methodology, data extraction and interpretation, supervision of the study, critical review of the manuscript, writing the original draft, and approval of the final version of the manuscript. DO-M: data extraction and interpretation, writing the original draft, literature search, critical review of the manuscript, and approval of the final version of the manuscript. CAA-O: design and conception of the research idea, literature search, data extraction and interpretation, critical review of the manuscript, writing the original draft, and approval of the final version of the manuscript.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Simental-Mendía, M., Ortega-Mata, D. & Acosta-Olivo, C.A. Platelet-Rich Plasma for Knee Osteoarthritis: What Does the Evidence Say?. Drugs Aging 40, 585–603 (2023). https://doi.org/10.1007/s40266-023-01040-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-023-01040-6

Navigation