Meta-analysis| Volume 33, ISSUE 3, P659-670.e1, March 2017

Download started.


Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials

Published:December 22, 2016DOI:


      To use meta-analysis techniques to evaluate the efficacy and safety of platelet-rich plasma (PRP) injections for the treatment knee of osteoarthritis (OA).


      We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane database through April 2016 to identify Level I randomized controlled trials that evaluated the clinical efficacy of PRP versus control treatments for knee OA. The primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores. The primary outcomes were compared with their minimum clinically important differences (MCID)—defined as the smallest difference perceived as important by the average patient.


      We included 10 randomized controlled trials with a total of 1069 patients. Our analysis showed that at 6 months postinjection, PRP and hyaluronic acid (HA) had similar effects with respect to pain relief (WOMAC pain score) and functional improvement (WOMAC function score, WOMAC total score, International Knee Documentation Committee score, Lequesne score). At 12 months postinjection, however, PRP was associated with significantly better pain relief (WOMAC pain score, mean difference −2.83, 95% confidence interval [CI] −4.26 to −1.39, P = .0001) and functional improvement (WOMAC function score, mean difference −12.53, 95% CI −14.58 to −10.47, P  < .00001; WOMAC total score, International Knee Documentation Committee score, Lequesne score, standardized mean difference 1.05, 95% CI 0.21-1.89, P = .01) than HA, and the effect sizes of WOMAC pain and function scores at 12 months exceeded the MCID (−0.79 for WOMAC pain and −2.85 for WOMAC function score). Compared with saline, PRP was more effective for pain relief (WOMAC pain score) and functional improvement (WOMAC function score) at 6 months and 12 months postinjection, and the effect sizes of WOMAC pain and function scores at 6 months and 12 months exceeded the MCID. We also found that PRP did not increase the risk of adverse events compared with HA and saline.


      Current evidence indicates that, compared with HA and saline, intra-articular PRP injection may have more benefit in pain relief and functional improvement in patients with symptomatic knee OA at 1 year postinjection.

      Level of Evidence

      Level I, meta-analysis of Level I studies.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Cross M.
        • Smith E.
        • Hoy D.
        • et al.
        The global burden of hip and knee osteoarthritis: Estimates from the global burden of disease 2010 study.
        Ann Rheum Dis. 2014; 73: 1323-1330
        • Haywood L.
        • Mcwilliams D.F.
        • Pearson C.I.
        • et al.
        Inflammation and angiogenesis in osteoarthritis.
        Arthritis Rheum. 2003; 48: 2173-2177
        • Dieppe P.A.
        • Lohmander L.S.
        Pathogenesis and management of pain in osteoarthritis.
        Lancet. 2005; 365: 965-973
        • Johnson V.L.
        • Hunter D.J.
        The epidemiology of osteoarthritis.
        Best Pract Res Clin Rheumatol. 2014; 28: 5-15
        • Carr A.J.
        • Robertsson O.
        • Graves S.
        • et al.
        Knee replacement.
        Lancet. 2012; 379: 1331-1340
        • Bijlsma J.W.
        • Berenbaum F.
        • Lafeber F.P.
        Osteoarthritis: An update with relevance for clinical practice.
        Lancet. 2011; 377: 2115-2126
        • Richmond J.
        • Hunter D.
        • Irrgang J.
        • et al.
        American Academy of Orthopaedic Surgeons clinical practice guideline on the treatment of osteoarthritis (OA) of the knee.
        J Bone Joint Surg Am. 2010; 92: 990-993
        • McAlindon T.E.
        • Bannuru R.R.
        • Sullivan M.C.
        • et al.
        OARSI guidelines for the non-surgical management of knee osteoarthritis.
        Osteoarthritis Cartilage. 2014; 22: 363-388
        • Boswell S.G.
        • Cole B.J.
        • Sundman E.A.
        • Karas V.
        • Fortier L.A.
        Platelet-rich plasma: A milieu of bioactive factors.
        Arthroscopy. 2012; 28: 429-439
        • Sundman E.A.
        • Cole B.J.
        • Karas V.
        • et al.
        The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis.
        Am J Sports Med. 2014; 42: 35-41
        • Cugat R.
        • Cusco X.
        • Seijas R.
        • et al.
        Biologic enhancement of cartilage repair: The role of platelet-rich plasma and other commercially available growth factors.
        Arthroscopy. 2015; 31: 777-783
        • Spreafico A.
        • Chellini F.
        • Frediani B.
        • et al.
        Biochemical investigation of the effects of human platelet releasates on human articular chondrocytes.
        J Cell Biochem. 2009; 108: 1153-1165
        • Anitua E.
        • Sanchez M.
        • Orive G.
        • Andia I.
        The potential impact of the preparation rich in growth factors (PRGF) in different medical fields.
        Biomaterials. 2007; 28: 4551-4560
        • Pettersson S.
        • Wettero J.
        • Tengvall P.
        • Kratz G.
        Human articular chondrocytes on macroporous gelatin microcarriers form structurally stable constructs with blood-derived biological glues in vitro.
        J Tissue Eng Regen Med. 2009; 3: 450-460
        • Kon E.
        • Filardo G.
        • Di Martino A.
        • Marcacci M.
        Platelet-rich plasma (PRP) to treat sports injuries: Evidence to support its use.
        Knee Surg Sports Traumatol Arthrosc. 2011; 19: 516-527
        • Milano G.
        • Deriu L.
        • Sanna Passino E.
        • et al.
        Repeated platelet concentrate injections enhance reparative response of microfractures in the treatment of chondral defects of the knee: An experimental study in an animal model.
        Arthroscopy. 2012; 28: 688-701
        • Kon E.
        • Mandelbaum B.
        • Buda R.
        • et al.
        Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early degeneration to osteoarthritis.
        Arthroscopy. 2011; 27: 1490-1501
        • Filardo G.
        • Kon E.
        • Di Martino 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: 229
        • Spakova T.
        • Rosocha J.
        • Lacko M.
        • Harvanova D.
        • Gharaibeh A.
        Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid.
        Am J Phys Med Rehabil. 2012; 91: 411-417
      1. Higgins J. Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. 2011. Accessed April 30, 2016.

        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement.
        BMJ. 2009; 339: b2535
        • Altman R.
        • Asch E.
        • Bloch D.
        • et al.
        Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee.
        Arthritis Rheum. 1986; 29: 1039-1049
        • McConnell S.
        • Kolopack P.
        • Davis A.M.
        The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): A review of its utility and measurement properties.
        Arthritis Rheum. 2001; 45: 453-461
        • Higgins L.D.
        • Taylor M.K.
        • Park D.
        • et al.
        Reliability and validity of the International Knee Documentation Committee (IKDC) Subjective Knee Form.
        Joint Bone Spine. 2007; 74: 594-599
        • Lequesne M.G.
        • Mery C.
        • Samson M.
        • Gerard P.
        Indexes of severity for osteoarthritis of the hip and knee. Validation—value in comparison with other assessment tests.
        Scand J Rheumatol Suppl. 1987; 65: 85-89
        • Landis J.R.
        • Koch G.G.
        The measurement of observer agreement for categorical data.
        Biometrics. 1977; 33: 159-174
        • Doganay Erdogan B.
        • Leung Y.Y.
        • Pohl C.
        • Tennant A.
        • Conaghan P.G.
        Minimal clinically important difference as applied in rheumatology: An OMERACT Rasch Working Group systematic review and critique.
        J Rheumatol. 2016; 43: 194-202
        • Jaeschke R.
        • Singer J.
        • Guyatt G.H.
        Measurement of health status. Ascertaining the minimal clinically important difference.
        Control Clin Trials. 1989; 10: 407-415
        • Angst F.
        • Aeschlimann A.
        • Stucki G.
        Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities.
        Arthritis Rheum. 2001; 45: 384-391
        • Tubach F.
        • Ravaud P.
        • Martin-Mola E.
        • et al.
        Minimum clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: Results from a prospective multinational study.
        Arthritis Care Res (Hoboken). 2012; 64: 1699-1707
        • Hmamouchi I.
        • Allali F.
        • Tahiri L.
        • et al.
        Clinically important improvement in the WOMAC and predictor factors for response to non-specific non-steroidal anti-inflammatory drugs in osteoarthritic patients: a prospective study.
        BMC Res Notes. 2012; 5: 58
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Begg C.B.
        • Mazumdar M.
        Operating characteristics of a rank correlation test for publication bias.
        Biometrics. 1994; 50: 1088-1101
        • 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
      2. Duymus TM, Mutlu S, Dernek B, Komur B, Aydogmus S, Kesiktas FN. Choice of intra-articular injection in treatment of knee osteoarthritis: Platelet-rich plasma, hyaluronic acid or ozone options [published online April 7, 2016]. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-016-4110-5 .

        • Filardo G.
        • Di Matteo B.
        • Di Martino A.
        • et al.
        Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial.
        Am J Sports Med. 2015; 43: 1575-1582
      3. Gormeli G, Gormeli CA, Ataoglu B, Colak C, Aslanturk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: A randomized, double-blind, placebo-controlled trial [published online August 2, 2015]. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-015-3705-6.

        • Patel S.
        • Dhillon M.S.
        • 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: 356-364
        • Paterson K.L.
        • Nicholls M.
        • Bennell K.L.
        • Bates D.
        Intra-articular injection of photo-activated platelet-rich plasma in patients with knee osteoarthritis: A double-blind, randomized controlled pilot study.
        BMC Musculoskelet Disord. 2016; 17: 67
        • Raeissadat S.A.
        • Rayegani S.M.
        • Hassanabadi H.
        • et al.
        Knee osteoarthritis injection choices: Platelet-rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial).
        Clin Med Insights Arthritis Musculoskelet Disord. 2015; 8: 1-8
        • Sanchez M.
        • Fiz N.
        • Azofra J.
        • et al.
        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. 2012; 28: 1070-1078
        • Smith P.A.
        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. 2016; 44: 884-891
        • Vaquerizo V.
        • Plasencia M.A.
        • Arribas I.
        • et al.
        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. 2013; 29: 1635-1643
        • Lopez-Vidriero E.
        • Goulding K.A.
        • Simon D.A.
        • Sanchez M.
        • Johnson D.H.
        The use of platelet-rich plasma in arthroscopy and sports medicine: Optimizing the healing environment.
        Arthroscopy. 2010; 26: 269-278
        • Mei-Dan O.
        • Carmont M.R.
        • Laver L.
        • Mann G.
        • Maffulli N.
        • Nyska M.
        Platelet-rich plasma or hyaluronate in the management of osteochondral lesions of the talus.
        Am J Sports Med. 2012; 40: 534-541
        • Warth R.J.
        • Dornan G.J.
        • James E.W.
        • Horan M.P.
        • Millett P.J.
        Clinical and structural outcomes after arthroscopic repair of full-thickness rotator cuff tears with and without platelet-rich product supplementation: A meta-analysis and meta-regression.
        Arthroscopy. 2015; 31: 306-320
        • Figueroa D.
        • Figueroa F.
        • Calvo R.
        • Vaisman A.
        • Ahumada X.
        • Arellano S.
        Platelet-rich plasma use in anterior cruciate ligament surgery: Systematic review of the literature.
        Arthroscopy. 2015; 31: 981-988
        • Ornetti P.
        • Nourissat G.
        • Berenbaum F.
        • Sellam J.
        • Richette P.
        • Chevalier X.
        Does platelet-rich plasma have a role in the treatment of osteoarthritis?.
        Joint Bone Spine. 2016; 83: 31-36
        • Petrera M.
        • De Croos J.N.
        • Iu J.
        • Hurtig M.
        • Kandel R.A.
        • Theodoropoulos J.S.
        Supplementation with platelet-rich plasma improves the in vitro formation of tissue-engineered cartilage with enhanced mechanical properties.
        Arthroscopy. 2013; 29: 1685-1692
        • Kreuz P.C.
        • Kruger J.P.
        • Metzlaff S.
        • et al.
        Platelet-rich plasma preparation types show impact on chondrogenic differentiation, migration, and proliferation of human subchondral mesenchymal progenitor cells.
        Arthroscopy. 2015; 31: 1951-1961
        • Filardo G.
        • Kon E.
        • Buda R.
        • et al.
        Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis.
        Knee Surg Sports Traumatol Arthrosc. 2011; 19: 528-535
        • Meheux C.J.
        • McCulloch P.C.
        • Lintner D.M.
        • Varner K.E.
        • Harris J.D.
        Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: A systematic review.
        Arthroscopy. 2016; 32: 495-505
        • Martin P.
        • Leibovich S.J.
        Inflammatory cells during wound repair: The good, the bad and the ugly.
        Trends Cell Biol. 2005; 15: 599-607
        • Scott A.
        • Khan K.M.
        • Roberts C.R.
        • Cook J.L.
        • Duronio V.
        What do we mean by the term “inflammation”? A contemporary basic science update for sports medicine.
        Br J Sports Med. 2004; 38: 372-380
        • Wells G.
        • Beaton D.
        • Shea B.
        • et al.
        Minimal clinically important differences: Review of methods.
        J Rheumatol. 2001; 28: 406-412
        • Wells G.
        • Anderson J.
        • Beaton D.
        • et al.
        Minimal clinically important difference module: Summary, recommendations, and research agenda.
        J Rheumatol. 2001; 28: 452-454
        • Crosby R.D.
        • Kolotkin R.L.
        • Williams G.R.
        Defining clinically meaningful change in health-related quality of life.
        J Clin Epidemiol. 2003; 56: 395-407
        • Zlowodzki M.
        • Bhandari M.
        Outcome measures and implications for sample-size calculations.
        J Bone Joint Surg Am. 2009; 91: 35-40
        • Khoshbin A.
        • Leroux T.
        • Wasserstein 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: 2037-2048
        • Laudy A.B.
        • Bakker E.W.
        • Rekers M.
        • Moen M.H.
        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
        • Moen M.
        • Weir A.
        • Bakker E.
        • Rekers M.
        • Laudy G.
        Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: An updated systematic review and meta-analysis.
        Osteoarthritis Cartilage. 2016; 24: S520-S521
        • Chang K.V.
        • Hung C.Y.
        • Aliwarga F.
        • Wang T.G.
        • Han D.S.
        • Chen W.S.
        Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: A systematic review and meta-analysis.
        Arch Phys Med Rehabil. 2014; 95: 562-575