Platelet-Rich Plasma Provides Greater Pain Relief and Functional Improvement Than Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Abstract

Knee osteoarthritis is among the leading causes of pain-related disability in adults, and intra-articular injection occupies an established niche between conservative management and arthroplasty. Platelet-rich plasma (PRP) and hyaluronic acid (HA) are both in widespread clinical use, yet which agent should be preferred, and for which patients, remains unsettled. The efficacy and safety of intra-articular PRP were compared with those of intra-articular HA for pain and physical function in adults with symptomatic knee osteoarthritis, and study-level modifiers of the treatment effect were identified. PubMed/MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched from inception to 14 April 2026 without language or date restriction, supplemented by reference-list searching. Randomized controlled trials comparing intra-articular PRP with intra-articular HA in adults with knee osteoarthritis and reporting the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score or the pain visual analogue scale (VAS) at 4 weeks or later were eligible. Two reviewers independently screened, extracted data and appraised each trial with the Cochrane Risk of Bias 2.0 tool. Mean differences (MDs) were pooled using random-effects models; heterogeneity was explored through pre-specified subgroup analyses (PRP leukocyte content, injection number, osteoarthritis severity, follow-up duration), sensitivity analyses and meta-regression; and certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty-eight randomized controlled trials comprising 2,685 participants were included. PRP was associated with greater improvement than HA in WOMAC total score (MD -8.14, 95% confidence interval [CI] -10.79 to -5.48; P < 0.00001; I² = 96%) and in pain VAS score (MD -7.89, 95% CI -12.90 to -2.89; P = 0.002; I² = 97%). Treatment effects were larger with leukocyte-poor PRP (P-interaction = 0.04), with multiple-injection protocols (P-interaction = 0.04) and in Kellgren-Lawrence grade I-II disease (P-interaction = 0.03). Meta-regression confirmed osteoarthritis severity (P = 0.03) and injection number (P = 0.04) as statistically significant effect modifiers, together explaining approximately 24% of the between-study variance. Restricting the analysis to trials at low risk of bias, and re-estimating the between-study variance with the restricted maximum likelihood estimator, attenuated but did not nullify the advantage of PRP. Egger's test showed no statistically significant funnel-plot asymmetry (WOMAC P = 0.21; VAS P = 0.24). Certainty of evidence was moderate for WOMAC and low for VAS. and Relevance: Intra-articular PRP produced greater functional improvement than HA with moderate certainty and greater pain relief with low certainty. The largest benefit is to be expected in mild-to-moderate disease treated with leukocyte-poor PRP in a multiple-injection protocol, and this profile should inform patient selection. HA remains a reasonable alternative, and standardized PRP preparation and reporting are required before firmer recommendations can be made. Level I, systematic review and meta-analysis of randomized controlled trials.