Efficacy and Safety of Plasma Rich in Growth Factors Intra-Articular Infiltrations in the Treatment of Knee Osteoarthritis


      The goal of this study was to systematically review the efficacy and safety of plasma rich in growth factors (PRGF) as a treatment for reducing symptoms in patients with knee osteoarthritis.


      A comprehensive and systematic literature search was conducted for PRGF treatment of knee osteoarthritis following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All the studies had to include a PRGF group and a control group. Pre- and post-treatment measures of joint pain, reduced function, and stiffness were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee score, Lequesne index, or number of Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI) responders, with a follow-up period of at least 4 weeks. An assessment of both the quality and risk of bias of the studies was conducted.


      The literature search yielded 91 citations, but only 5 were eligible publications that met the inclusion criteria (2 randomized controlled trials, 2 prospective studies, and 1 retrospective analysis). Two studies were rated as having a low risk of bias whereas 3 had a high risk. In both randomized controlled trials, it was observed that after 6 months of treatment, the number of patients with a pain reduction of more than 50% was significantly higher in the PRGF group. In 2 other studies, the patients treated with PRGF showed a significant pain reduction compared with the control group. The remaining variables (Western Ontario and McMaster Universities Osteoarthritis Index scale for pain, function, and stiffness; Lequesne index; Knee Injury and Osteoarthritis Outcome Score scale; and number of OMERACT-OARSI responders) showed a statistically significant superiority of the group treated with PRGF.


      The current clinical evidence suggests that PRGF intra-articular infiltrations in patients with knee osteoarthritis reduce pain and therefore are clinically efficacious in osteoarthritis treatment.

      Level of Evidence

      Level III, systematic review of Level I, II, and III studies.
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        • Felson D.T.
        Developments in the clinical understanding of osteoarthritis.
        Arthritis Res Ther. 2009; 11: 203
        • Goldring M.B.
        • Marcu K.B.
        Epigenomic and microRNA-mediated regulation in cartilage development, homeostasis, and osteoarthritis.
        Trends Mol Med. 2012; 18: 109-118
        • Sandell L.J.
        Etiology of osteoarthritis: Genetics and synovial joint development.
        Nat Rev Rheumatol. 2012; 8: 77-89
        • Pereira D.
        • Peleteiro B.
        • Araujo J.
        • Branco J.
        • Santos R.A.
        • Ramos E.
        The effect of osteoarthritis definition on prevalence and incidence estimates: A systematic review.
        Osteoarthritis Cartilage. 2011; 19: 1270-1285
        • Wielage R.C.
        • Myers J.A.
        • Klein R.W.
        • Happich M.
        Cost-effectiveness analyses of osteoarthritis oral therapies: A systematic review.
        Appl Health Econ Health Policy. 2013; 11: 593-618
        • Hiligsmann M.
        • Cooper C.
        • Arden N.
        • et al.
        Health economics in the field of osteoarthritis: An expert's consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).
        Semin Arthritis Rheum. 2013; 43: 303-313
      1. Filardo G, Kon E, Roffi A, Di Matteo B, Merli ML, Marcacci M. Platelet-rich plasma: Why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration. Knee Surg Sports Traumatol Arthrosc in press, available online 26 November, 2013. http//

        • Smyth N.A.
        • Murawski C.D.
        • Fortier L.A.
        • Cole B.J.
        • Kennedy J.G.
        Platelet-rich plasma in the pathologic processes of cartilage: Review of basic science evidence.
        Arthroscopy. 2013; 29: 1399-1409
        • Zhu Y.
        • Yuan M.
        • Meng H.Y.
        • et al.
        Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: A review.
        Osteoarthritis Cartilage. 2013; 21: 1627-1637
        • Anitua E.
        • Sánchez M.
        • Orive G.
        • Padilla S.
        A biological therapy to osteoarthritis treatment using platelet-rich plasma.
        Expert Opin Biol Ther. 2013; 13: 1161-1172
        • Anitua E.
        • Prado R.
        • Sánchez M.
        • Orive G.
        Platelet-rich plasma: Preparation and formulation.
        Oper Tech Orthop. 2012; 22: 25-32
        • Dohan Ehrenfest D.M.
        • Rasmusson L.
        • Albrektsson T.
        Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).
        Trends Biotechnol. 2009; 27: 158-167
        • Mishra A.
        • Harmon K.
        • Woodall J.
        • Vieira A.
        Sports medicine applications of platelet rich plasma.
        Curr Pharm Biotechnol. 2012; 13: 1185-1195
        • DeLong J.M.
        • Russell R.P.
        • Mazzocca A.D.
        Platelet-rich plasma: The PAW classification system.
        Arthroscopy. 2012; 28: 998-1009
        • Chahal J.
        • Van Thiel G.S.
        • Mall N.
        • et al.
        The role of platelet-rich plasma in arthroscopic rotator cuff repair: A systematic review with quantitative synthesis.
        Arthroscopy. 2012; 28: 1718-1727
        • Sheth U.
        • Simunovic N.
        • Klein G.
        • et al.
        Efficacy of autologous platelet-rich plasma use for orthopaedic indications: A meta-analysis.
        J Bone Joint Surg Am. 2012; 94: 298-307
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration.
        BMJ. 2009; 339: b2700
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • Group P.
        Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement.
        PLoS Med. 2009; 6: e1000097
        • Altman R.
        • Asch E.
        • Bloch D.
        • et al.
        Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.
        Arthritis Rheum. 1986; 29: 1039-1049
        • Higgins J.P.
        • Altman D.G.
        • Gotzsche P.C.
        • et al.
        The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • Atkins D.
        • Best D.
        • Briss P.A.
        • et al.
        Grading quality of evidence and strength of recommendations.
        BMJ. 2004; 328: 1490
        • Guyatt G.H.
        • Oxman A.D.
        • Vist G.E.
        • et al.
        GRADE: An emerging consensus on rating quality of evidence and strength of recommendations.
        BMJ. 2008; 336: 924-926
        • Jang S.J.
        • Kim J.D.
        • Cha S.S.
        Platelet-rich plasma (PRP) injections as an effective treatment for early osteoarthritis.
        Eur J Orthop Surg Traumatol. 2013; 23: 573-580
        • 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
        • 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
        • Darabos N.
        • Haspl M.
        • Moser C.
        • Darabos A.
        • Bartolek D.
        • Groenemeyer D.
        Intraarticular application of autologous conditioned serum (ACS) reduces bone tunnel widening after ACL reconstructive surgery in a randomized controlled trial.
        Knee Surg Sports Traumatol Arthrosc. 2011; 19: S36-S46
        • Kon E.
        • Buda R.
        • Filardo G.
        • et al.
        Platelet-rich plasma: Intra-articular knee injections produced favorable results on degenerative cartilage lesions.
        Knee Surg Sports Traumatol Arthrosc. 2010; 18: 472-479
        • Gobbi A.
        • Karnatzikos G.
        • Mahajan V.
        • Malchira S.
        Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: Preliminary results in a group of active patients.
        Sports Health. 2012; 4: 162-172
        • 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
        • Sampson S.
        • Reed M.
        • Silvers H.
        • Meng M.
        • Mandelbaum B.
        Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: A pilot study.
        Am J Phys Med Rehabil. 2010; 89: 961-969
        • 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
        • 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
        • Wang-Saegusa A.
        • Cugat R.
        • Ares O.
        • Seijas R.
        • Cusco X.
        • Garcia-Balletbo M.
        Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life.
        Arch Orthop Trauma Surg. 2011; 131: 311-317
        • Filardo G.
        • Kon E.
        • Pereira Ruiz M.T.
        • et al.
        Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: Single- versus double-spinning approach.
        Knee Surg Sports Traumatol Arthrosc. 2012; 20: 2082-2091
        • Sánchez M.
        • Anitua E.
        • Azofra J.
        • Aguirre J.J.
        • Andia I.
        Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: A retrospective cohort study.
        Clin Exp Rheumatol. 2008; 26: 910-913
        • Sánchez 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
        • Say F.
        • Gurler D.
        • Yener K.
        • Bulbul M.
        • Malkoc M.
        Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis.
        Acta Chir Orthop Traumatol Cech. 2013; 80: 278-283
        • 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
        • 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
        • 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
        • Dold A.P.
        • Zywiel M.G.
        • Taylor D.W.
        • Dwyer T.
        • Theodoropoulos J.
        Platelet-rich plasma in the management of articular cartilage pathology: A systematic review.
        Clin J Sport Med. 2014; 24: 31-43
        • Coombes B.K.
        • Bisset L.
        • Vicenzino B.
        Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: A systematic review of randomised controlled trials.
        Lancet. 2010; 376: 1751-1767
        • de Vos R.J.
        • van Veldhoven P.L.
        • Moen M.H.
        • Weir A.
        • Tol J.L.
        • Maffulli N.
        Autologous growth factor injections in chronic tendinopathy: A systematic review.
        Br Med Bull. 2010; 95: 63-77
        • Taylor D.W.
        • Petrera M.
        • Hendry M.
        • Theodoropoulos J.S.
        A systematic review of the use of platelet-rich plasma in sports medicine as a new treatment for tendon and ligament injuries.
        Clin J Sport Med. 2011; 21: 344-352
        • Vavken P.
        • Sadoghi P.
        • Murray M.M.
        The effect of platelet concentrates on graft maturation and graft-bone interface healing in anterior cruciate ligament reconstruction in human patients: A systematic review of controlled trials.
        Arthroscopy. 2011; 27: 1573-1583
        • Ahmad Z.
        • Brooks R.
        • Kang S.N.
        • et al.
        The effect of platelet-rich plasma on clinical outcomes in lateral epicondylitis.
        Arthroscopy. 2013; 29: 1851-1862
        • de Vos R.J.
        • Windt J.
        • Weir A.
        Strong evidence against platelet-rich plasma injections for chronic lateral epicondylar tendinopathy: A systematic review.
        Br J Sports Med. 2014; 48: 952-956
        • Hamid M.S.
        • Yusof A.
        Mohamed Ali MR. Platelet-rich plasma (PRP) for acute muscle injury: A systematic review.
        PLoS One. 2014; 9: e90538
        • Vannini F.
        • Di Matteo B.
        • Filardo G.
        • Kon E.
        • Marcacci M.
        • Giannini S.
        Platelet-rich plasma for foot and ankle pathologies: A systematic review.
        Foot Ankle Surg. 2014; 20: 2-9
      2. Anitua E, Sánchez M, Prado R, Orive G. The type of platelet-rich plasma may influence the safety of the approach. Knee Surg Sports Traumatol Arthrosc in press, available online 9 May, 2012.

        • McCarrel T.M.
        • Minas T.
        • Fortier L.A.
        Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy.
        J Bone Joint Surg Am. 2012; 94: e1431-e1438
        • Sundman E.A.
        • Cole B.J.
        • Fortier L.A.
        Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma.
        Am J Sports Med. 2011; 39: 2135-2140
        • Andia I.
        • Maffulli N.
        Platelet-rich plasma for managing pain and inflammation in osteoarthritis.
        Nat Rev Rheumatol. 2013; 9: 721-730
        • Descalzi F.
        • Ulivi V.
        • Cancedda R.
        • et al.
        Platelet-rich plasma exerts antinociceptive activity by a peripheral endocannabinoid-related mechanism.
        Tissue Eng Part A. 2013; 19: 2120-2129
        • Andia I.
        • Abate M.
        Knee osteoarthritis: Hyaluronic acid, platelet-rich plasma or both in association?.
        Expert Opin Biol Ther. 2014; 14: 635-649
        • Bannuru R.R.
        • Natov N.S.
        • Dasi U.R.
        • Schmid C.H.
        • McAlindon T.E.
        Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis—Meta-analysis.
        Osteoarthritis Cartilage. 2011; 19: 611-619
        • Bellamy N.
        • Campbell J.
        • Robinson V.
        • Gee T.
        • Bourne R.
        • Wells G.
        Viscosupplementation for the treatment of osteoarthritis of the knee.
        Cochrane Database Syst Rev. 2006; : CD005321
        • 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