Younger age and platelet‐rich plasma characteristics influence short‐term outcomes in knee osteoarthritis, but independent effects remain uncertain: A systematic review with meta‐analysis and meta‐regression of placebo‐controlled randomised trials
Diego Delgado, Renato Andrade, Eluana Gomes, Tiago Lopes, Juan Azofra, João Espregueira‐Mendes, Mikel SánchezAbstract
Purpose
The goal of this systematic review with meta‐regression was to investigate the influence of different platelet‐rich plasma (PRP) composition and administration characteristics on the clinical results of intra‐articular PRP injections in patients with knee osteoarthritis (KOA) as compared to placebo.
Methods
Three databases were searched until 25 May 2025, to identify randomised placebo‐controlled trials of PRP injections in KOA. Population, PRP composition and administration characteristics and clinical scores data were collected. Clinical data were categorised into functional and pain scores and recorded at 6‐ and 12‐month follow‐up. Meta‐analysis comparing PRP to placebo was conducted using random‐effects model and summarised as standardised mean differences and 95% confidence intervals. Meta‐regression was conducted using patient‐related and PRP‐specific covariates.
Results
Twenty studies including 26 unique groups of PRP ( n = 1774) and 20 groups of placebo ( n = 1518). The PRP group showed statistically significant improved knee function and pain at 6 months and at 12 months (large effect, very low certainty). Higher platelet increase factor and activation with CaCl 2 were significantly associated with superior PRP results in knee function and pain at 6 months. Younger age and leucocyte‐rich PRP were significantly associated with improved knee function. However, PRP type and concentration factor were significantly correlated. No other moderator explained the superior PRP results at 6 months, and none at the 12‐month follow‐up.
Conclusions
Younger age, higher platelet increase factor, LR‐PRP and CaCl 2 activation were associated with greater short‐term improvements in meta‐regression analyses. Intra‐articular PRP injections appeared to be more effective than placebo in reducing pain and improving knee function at 6 and 12 months. However, the certainty of evidence was very low and due to interrelated PRP characteristics and limited reporting across studies, the independent contribution of individual factors remains uncertain, and these findings are still hypothesis‐generating rather than definitive evidence supporting specific PRP formulations.
Level of Evidence
Level I.