The use of platelet-rich plasma (PRP) for the treatment of osteoarthritis (OA) has demonstrated mixed clinical outcomes in randomized controlled trials when compared with hyaluronic acid (HA), an accepted nonsurgical treatment for symptomatic OA. Biological analysis of PRP has demonstrated an anti-inflammatory effect on the intra-articular environment.
To compare the clinical and biological effects of an intra-articular injection of PRP with those of an intra-articular injection of HA in patients with mild to moderate knee OA.
Randomized controlled trial; Level of evidence, 1.
A total of 111 patients with symptomatic unilateral knee OA received a series of either leukocyte-poor PRP or HA injections under ultrasound guidance. Clinical data were collected before treatment and at 4 time points across a 1-year period. Synovial fluid was also collected for analysis of proinflammatory and anti-inflammatory markers before treatment and at 12 and 24 weeks after treatment. Several measures were used to assess results: (1) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; (2) International Knee Documentation Committee (IKDC) subjective knee evaluation, visual analog scale (VAS) for pain, and Lysholm knee score; and (3) difference in intra-articular biochemical marker concentrations.
There were 49 patients randomized to treatment with PRP and 50 randomized to treatment with HA. No difference was seen between the groups in the primary outcome measure (WOMAC pain score). In the secondary outcome measure, linear contrasts identified a significantly higher IKDC score in the PRP group compared with the HA group at 24 weeks (mean ± standard error [SE], 65.5 ± 3.6 vs 55.8 ± 3.8, respectively; P = .013) and at final follow-up (52 weeks) (57.6 ± 3.37 vs 46.6 ± 3.76, respectively; P = .003). Linear contrasts also identified a statistically lower VAS score in the PRP group versus the HA group at 24 weeks (mean ± SE, 34.6 ± 3.24 vs 48.6 ± 3.7, respectively; P = .0096) and 52 weeks (44 ± 4.6 vs 57.3 ± 3.8, respectively; P = .0039). An examination of fixed effects showed that patients with mild OA and a lower body mass index had a statistically significant improvement in outcomes. In the biochemical analysis, differences between groups approached significance for interleukin-1β (mean ± SE, 0.14 ± 0.05 pg/mL [PRP] vs 0.34 ± 0.16 pg/mL [HA]; P = .06) and tumor necrosis factor α (0.08 ± 0.01 pg/mL [PRP] vs 0.2 ± 0.18 pg/mL [HA]; P = .068) at 12-week follow-up.
We found no difference between HA and PRP at any time point in the primary outcome measure: the patient-reported WOMAC pain score. Significant improvements were seen in other patient-reported outcome measures, with results favoring PRP over HA. Preceding a significant difference in subjective outcomes favoring PRP, there was a trend toward a decrease in 2 proinflammatory cytokines, which suggest that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms.
ClinicalTrials.gov (Identifier: NCT02588872).
|1.||Arroll, B, Goodyear-Smith, F. Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ. 2004;328(7444):869. Google Scholar, Crossref, Medline|
|2.||Badlani, N, Inoue, A, Healey, R. The protective effect of OP-1 on articular cartilage in the development of osteoarthritis. Osteoarthritis Cartilage. 2008;16(5):600–606. Google Scholar, Crossref, Medline|
|3.||Boswell, SG, Cole, BJ, Sundman, EA. Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy. 2012;28(3):429–439. Google Scholar, Crossref, Medline|
|4.||Brandl, A, Angele, P, Roll, C. Influence of the growth factors PDGF-BB, TGF-beta1 and bFGF on the replicative aging of human articular chondrocytes during in vitro expansion. J Orthop Res. 2010;28(3):354–360. Google Scholar, Medline|
|5.||Cerza, F, Carni, S, Carcangiu, A. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40(12):2822–2827. Google Scholar, Link, ISI|
|6.||Chevalier, X, Jerosch, J, Goupille, P. Single, intra-articular treatment with 6 mL hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010;69(1):113–119. Google Scholar, Crossref, Medline|
|7.||Chubinskaya, S, Hurtig, M, Rueger, DC. OP-1/BMP-7 in cartilage repair. Int Orthop. 2007;31(6):773–781. Google Scholar, Crossref, Medline|
|8.||Dillon, CF, Rasch, EK, Gu, Q. Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey 1991-94. J Rheumatol. 2006;33(11):2271–2279. Google Scholar, Medline|
|9.||Filardo, G, Kon, E, Buda, R. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011;19(4):528–535. Google Scholar, Crossref, Medline|
|10.||Filardo, G, Kon, E, Di Martino, A. 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. Google Scholar, Crossref, Medline|
|11.||Fortier, LA, Barker, JU, Strauss, EJ. The role of growth factors in cartilage repair. Clin Orthop Relat Res. 2011;469(10):2706–2715. Google Scholar, Crossref, Medline|
|12.||Greco, NJ, Anderson, AF, Mann, BJ. Responsiveness of the International Knee Documentation Committee subjective knee form in comparison to the Western Ontario and McMaster Universities Osteoarthritis Index, modified Cincinnati Knee Rating System, and Short Form 36 in patients with focal articular cartilage defects. Am J Sports Med. 2010;38(5):891–902. Google Scholar, Link, ISI|
|13.||Kapoor, M, Martel-Pelletier, J, Lajeunesse, D. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33–42. Google Scholar, Crossref, Medline|
|14.||Kirchner, M, Marshall, D. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage. 2006;14(2):154–162. Google Scholar, Crossref, Medline|
|15.||Kon, E, Buda, R, Filardo, G. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):472–479. Google Scholar, Crossref, Medline|
|16.||Kon, E, Mandelbaum, B, Buda, R. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy. 2011;27(11):1490–1501. Google Scholar, Crossref, Medline|
|17.||Lawrence, JT, Birmingham, J, Toth, AP. Emerging ideas: prevention of posttraumatic arthritis through interleukin-1 and tumor necrosis factor-alpha inhibition. Clin Orthop Relat Res. 2011;469(12):3522–3526. Google Scholar, Crossref, Medline|
|18.||Marx, RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10(4):225–228. Google Scholar, Crossref, Medline|
|19.||Patel, S, Dhillon, MS, Aggarwal, S. 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(2):356–364. Google Scholar, Link, ISI|
|20.||Petrella, RJ, Petrella, M. A prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intraarticular hyaluronic acid for osteoarthritis of the knee. J Rheumatol. 2006;33(5):951–956. Google Scholar, Medline|
|21.||Pham, T, Maillefert, JF, Hudry, C. Laterally elevated wedged insoles in the treatment of medial knee osteoarthritis: a two-year prospective randomized controlled study. Osteoarthritis Cartilage. 2004;12(1):46–55. Google Scholar, Crossref, Medline|
|22.||Riboh, JC, Saltzman, BM, Yanke, AB. 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. Google Scholar, Link|
|23.||Scanzello, CR, Umoh, E, Pessler, F. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease. Osteoarthritis Cartilage. 2009;17(8):1040–1048. Google Scholar, Crossref, Medline|
|24.||Spakova, T, Rosocha, J, Lacko, M. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012;91(5):411–417. Google Scholar, Crossref, Medline|
|25.||Vaquerizo, V, Plasencia, MÁ, Arribas, I. 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(10):1635–1643. Google Scholar, Crossref, Medline|
|26.||Zhang, W, Moskowitz, RW, Nuki, G. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–162. Google Scholar, Crossref, Medline|