Dhafer Alshehri, Raed M Sharaf, Abdulraheem A Almokhtar, Mohammed K Alamri
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.
IMPORTANCE: 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.
AIM OR OBJECTIVE: 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.
EVIDENCE REVIEW: 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.
FINDINGS: 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.
CONCLUSION: 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 OF EVIDENCE: Level I, systematic review and meta-analysis of randomized controlled trials.