Platelet-Rich Plasma Provides Small but Superior Short-term Pain Relief and Functional Improvement Compared With Hyaluronic Acid for the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Abstract

To compare the efficacy of platelet-rich plasma (PRP) versus hyaluronic acid (HA) in knee osteoarthritis and to identify preparation and application-related factors influencing outcomes. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020, this study was registered in the International Prospective Register of Systematic Reviews. PubMed, Embase, and Cochrane Library were searched to August 2025. Randomized controlled trials comparing intra-articular PRP and HA in knee osteoarthritis were included. Primary outcomes were pain and function scores (visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score, and International Knee Documentation Committee). Risk of bias was assessed with Cochrane RoB 1.0. Standardized mean differences with 95% confidence interval were pooled; subgroup and metaregression analyses explored platelet concentration, leukocyte enrichment, activation, and injection frequency. Twenty-one randomized controlled trials (1790 patients) were analyzed. At 3 and 6 months, PRP showed no significant advantage over HA in visual analog scale scores. At 12 months, however, PRP significantly reduced pain compared with HA (Standardized mean difference 0.76, P = .016). Western Ontario and McMaster Universities Osteoarthritis Index improvements favored PRP at all time points (P ≤ .001). No significant differences were observed in Knee Injury and Osteoarthritis Outcome Score or International Knee Documentation Committee. Subgroup analyses revealed that high-concentration, leukocyte-rich, and activated PRP were associated with superior outcomes at 12-month follow-up, whereas injection frequency showed no consistent effect. Metaregression confirmed platelet concentration as a positive predictor of treatment efficacy at 12 months. Based on the available evidence with follow-up up to 12 months, PRP was associated with small but statistically significant improvements in pain (visual analog scale) and Western Ontario and McMaster Universities Osteoarthritis Index scores compared with HA in patients with knee osteoarthritis, whereas no significant differences were observed in International Knee Documentation Committee or Knee Injury and Osteoarthritis Outcome Score outcomes. Subgroup and metaregression analyses suggested that platelet concentration, leukocyte content, and activation status may be associated with variability in treatment effects, although substantial heterogeneity and risk of bias were present across studies. These findings should be interpreted cautiously and reflect short-term to 12-month outcomes only. Level II, systematic review and meta-analysis of Level I and II studies.