PRP Injections for the Treatment of Knee Osteoarthritis: The Improvement Is Clinically Significant and Influenced by Platelet Concentration: A Meta-analysis of Randomized Controlled Trials

Abstract

Background: Platelet-rich plasma (PRP) has emerged as a promising therapeutic intervention for knee osteoarthritis (OA), attracting substantial clinical and research attention. However, the clinical relevance of the treatment benefit remains controversial.

Purpose: To evaluate the effectiveness of PRP compared with placebo in patients with knee OA in terms of minimal clinically important difference (MCID) and to investigate the possible influence of platelet concentration on the clinical outcome.

Study design: Meta-analysis. Level of evidence 1.

Methods: The search was conducted on 5 databases (PubMed, Cochrane Library, Scopus, Embase, Web of Science) using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were randomized controlled trials comparing PRP and placebo injections to treat knee OA, written in the English language, with no time limitation. The effects were quantified at 1-, 3-, 6-, and 12-month follow-up points. Visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used, with subanalyses based on platelet concentration performed using a 1,000,000 ± 20% platelets/µL cutoff. The MCID values (VAS, 1.37; WOMAC, 6.4) were used to interpret clinical improvement. The articles' quality was assessed using the Revised Tool for Risk of Bias in Randomized Trials and the Grading of Recommendations Assessment, Development and Evaluation guidelines.

Results: Among the 5499 articles retrieved, 18 randomized controlled trials (1995 patients) were included. PRP presented statistically superior improvements in VAS and WOMAC scores compared with placebo at all follow-up points, exceeding the MCID at 3- and 6-month follow-up points for VAS and at all follow-up points for WOMAC. The subanalysis based on platelet concentration showed that high-platelet PRP provided clinically significant pain relief with the improvement exceeding the MCID compared with placebo at 3-, 6-, and 12-month follow-up points. In contrast, low-platelet PRP failed to offer a clinically perceivable benefit in terms of VAS score. WOMAC results showed that both products provided a clinically significant improvement at 3 and 6 months of follow-up. This benefit was maintained up to the 12-month follow-up in the high-platelet group but not in the low-platelet group, where the improvement compared with placebo did not reach statistical significance.

Conclusion: This meta-analysis showed that PRP offered clinically relevant functional improvement at 1-, 3-, 6-, and 12-month follow-up points and pain relief at 3- and 6-month follow-up points compared with placebo for the treatment of knee OA. Platelet concentration was found to influence treatment efficacy, with high-platelet PRP providing superior pain relief and more durable functional improvement compared with low-platelet PRP.

Keywords: OA; PRP; knee; osteoarthritis; placebo; platelet-rich plasma.

Figure 1.

PRISMA flowchart of the study selection process. OA, osteoarthritis; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, randomized controlled trial.

Figure 2.

Number of randomized controlled trials published over time on the comparison of platelet-rich plasma and placebo for knee osteoarthritis.

Figure 3.

Forest plot of the individual studies and pooled weighted mean difference (MD) for Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) improvement, including 95% CI. Platelet-rich plasma (PRP) produced statistically and clinically superior improvement compared with placebo at all follow-up points, with these improvements exceeding the 6.4 minimal clinically important difference (MCID). The subanalysis based on platelet concentration showed that both products provided a clinically significant improvement at 3- and 6-month follow-up points, but this benefit was maintained up to the 12-month follow-up only in the high-platelet group. The middle diamond for the 1-month follow-up point and the top diamond for the 12-month follow-up point indicate not statistically significant; all other diamonds indicate statistically and clinically significant (MD > MCID).

Figure 4.

Forest plot of the individual studies and pooled weighted mean difference (MD) for visual analog scale (VAS) pain improvement, including 95% CI. Platelet-rich plasma (PRP) produced statistically superior improvement compared with placebo at all follow-up points, with these improvements exceeding the 1.37 minimal clinically important difference (MCID) at 3- and 6-month follow-up points. The subanalysis based on platelet concentration showed that the improvement of high-platelet PRP compared with placebo exceeded the MCID at 3, 6, and 12 months of follow-up, whereas low-platelet PRP failed to offer such clinically perceivable benefits. The top and middle diamonds for the 1-month follow-up point and the top diamond for the 3- and 12-month follow-up points indicate not statistically significant; the top diamond for the 6-month follow-up point and the bottom diamond for the 1- and 12-month follow-up points indicate statistically but not clinically significant (MD < MCID); the middle diamond for the 3-, 6-, and 12-month follow-up points and the bottom diamond for the 3- and 6-month follow-up points indicate statistically and clinically significant (MD > MCID).

Figure 5.

Cochrane risk of bias tool for randomized trials Version 2 (RoB 2.0). D, Domain; +, low risk; −, some concerns; X, high risk. RoB, Revised Tool for Risk of Bias in Randomized Trials.