Meta-analysis| Volume 37, ISSUE 4, P1277-1287.e1, April 2021

Platelet-Rich Plasma Combined With Hyaluronic Acid Improves Pain and Function Compared With Hyaluronic Acid Alone in Knee Osteoarthritis: A Systematic Review and Meta-analysis

Published:December 02, 2020DOI:


      To evaluate the efficacy of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) injections versus HA injections alone for the management of knee osteoarthritis (OA).


      This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized-controlled trials and observational studies directly comparing combined PRP-HA injections with HA injections alone were identified through a search of PubMed, Scopus, and Cochrane Central databases from inception to May 2020. A random effects model meta-analysis was conducted and the I2 statistic was used to assess for heterogeneity.


      Four studies comprising 377 patients (PRP-HA: 193, HA: 184) with knee OA ranging from I-IV Kellgren–Lawrence grading scale were included. The final follow-up was 12 months in 3 studies and 6 months in 1 study. Patients who received PRP combined with HA had significantly greater improvements compared with those injected with HA alone in terms of visual analog scale scores at 3-month (standardized mean difference [SMD] 1.13; 95% confidence interval [CI] 0.56-1.70; I2 = 56.7%; P < .001), 6-month (SMD 1.08; 95% CI 0.54-1.62; I2 = 67.9%; P < .001), and 12-month (SMD 1.13; 95% CI 0.74-1.52; I2 = 0.0%; P < .001) and 12-month Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical functioning (SMD 0.91; 95% CI 0.65-1.17; I2 = 0.0%; P < .001) and 12-month WOMAC stiffness (SMD 1.09; 95% CI 0.80-1.38; I2 = 0.0%; P < .001) scores. No difference was identified in terms of 12-month WOMAC pain score (SMD 0.36; 95% CI –0.19 to 0.91; I2 = 74.1%; P = .195).


      Symptomatic patients with knee OA who were injected with a combination of PRP and HA demonstrated greater improvement in pain and function compared with patients who received HA injections only, as assessed by 3-, 6-, and 12-month visual analog scale scores and 12-month WOMAC physical function and stiffness scores. This study provides encouraging evidence for the use of the combined PRP-HA injections in the management of symptomatic patients with knee OA.

      Level of Evidence

      III (meta-analysis of randomized and non-randomized comparative trials).
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