Efficacy and Safety of Platelet-Rich Plasma in Knee Osteoarthritis: Umbrella Meta-Analysis Based on Clinical Evidence, Methodological Quality and Therapeutic Positioning

Abstract

Background/Objectives: Despite being a standard biological therapy for knee osteoarthritis, inconsistent results across studies—due to varied protocols—have obscured the clinical standing of platelet-rich plasma. This meta-analysis evaluates the efficacy and safety of PRP for pain, function, and adverse events, and examines the potential benefits of combining it with hyaluronic acid. Methods: An umbrella review was conducted following the PRIOR (Preferred Reporting Items for Umbrella Reviews) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Meta-analyses evaluating PRP in knee osteoarthritis were included. Quantitative estimates of pain, function, and safety were extracted. Random-effects models were applied when possible. Methodological quality was assessed using AMSTAR 2, and study overlaps were assessed using the CCA method. Publication bias was analyzed using a funnel plot. Results: The meta-analyses included consistently showed the superiority of PRP over hyaluronic acid and placebo in reducing pain and improving function. Pooled estimates indicated clinically relevant improvements, especially in mild-to-moderate osteoarthritis. The combination of PRP and hyaluronic acid demonstrated superior functional recovery and a potential reduction in adverse events compared to PRP monotherapy. The overall safety profile was favorable. Conclusions: PRP is an effective and safe therapy for knee osteoarthritis, with consistent evidence of superiority over conventional intra-articular treatments. Combined PRP and HA administration suggests superior clinical efficacy compared to monotherapy. Standardization of protocols and appropriate patient selection will be key in future clinical guidelines.