The Efficacy of Platelet-Rich Plasma Alone Versus Platelet-Rich Plasma Combined With Hyaluronic Acid in the Treatment Of Knee Osteoarthritis: A Systematic Review and Meta-Analysis
E. Pasqualotto, T. Pasqualotto, L. Lunelli, S. Da Silva, L.S. Migliardi, F.B. De SousaObjectives:
To compare the clinical efficacy of platelet-rich plasma (PRP) alone versus PRP combined with hyaluronic acid (HA) in adults with knee osteoarthritis.
Methods:
PubMed, Embase, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) published up to December 2025 comparing PRP alone with PRP combined with HA in patients with knee osteoarthritis. Mean differences (MDs) were calculated for continuous outcomes, with 95% confidence intervals (CIs).
Results:
A total of 10 RCTs comprising 822 patients were included. The PRP + HA group showed statistically significant superiority for VAS at 6 months (MD 0.49 mm; 95% CI 0.07 to 0.90), IKDC at 3 months (MD -4.48 points; 95% CI -7.87 to -1.08) and 6 months (MD -4.86 points; 95% CI -8.09 to -1.62), WOMAC total score at 12 months (MD 4.28 points; 95% CI 1.71 to 6.85), WOMAC physical function at 12 months (MD 4.56 points; 95% CI 2.23 to 6.90), and WOMAC stiffness at 1 month (MD -0.48 points; 95% CI -0.95 to -0.01). No significant differences were observed between groups for the Lequesne Index, KOOS scores, or WOMAC pain subscale at any follow-up interval.
Conclusion:
PRP combined with HA demonstrated modest, time-dependent improvements in selected outcomes compared with PRP alone in knee osteoarthritis, particularly for pain and functional measures at mid-term follow-up. However, no consistent superiority was observed across all clinical outcomes or time points. Further high-quality randomized trials are needed to clarify the long-term clinical benefits of combination therapy.