Long-term efficacy of platelet-rich plasma for knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

Background and Aims: Platelet-rich plasma (PRP) has gained attention as a regenerative therapy for knee osteoarthritis (KOA), but its long-term efficacy and optimal dosing remain under discussion. The objective of this study was to evaluate the long-term clinical effectiveness, safety, and structural outcomes of intra-articular PRP compared with hyaluronic acid (HA), saline, ozone, and corticosteroid injections in mild-to-moderate KOA. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) published up to December 2024 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Ten high-quality RCTs ( n = 1,756) met inclusion criteria. Primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS), and International Knee Documentation Committee scores; magnetic resonance imaging-assessed cartilage changes and cytokine modulation were analyzed when available. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results: PRP produced greater improvement in pain and function than HA, saline, ozone, or corticosteroids at 6–12 months (WOMAC improvement ≈ 40–45% vs. ≤30% for HA; VAS reduction ≈ 3.0–3.5 points vs. ≤2.0). Multi-dose (three-injection) regimens showed superior and more durable effects compared with single or double injections, maintaining clinically important benefits up to 24 months. The largest multicenter RCT (Chu et al ., 2022) demonstrated approximately 50% slower cartilage volume loss with PRP versus saline over 5 years. All studies reported only mild, transient adverse events. Conclusion: PRP, particularly in triple-injection protocols, offers sustained pain relief, functional improvement, and potential structural protection compared with standard injectables in early-to-moderate KOA, with an excellent safety profile.