Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis

Am J Sports Med. 2017 Feb;45(2):339-346. doi: 10.1177/0363546516665809. Epub 2016 Oct 21.


Background: The use of platelet-rich plasma (PRP) for the treatment of osteoarthritis (OA) has demonstrated mixed clinical outcomes in randomized controlled trials when compared with hyaluronic acid (HA), an accepted nonsurgical treatment for symptomatic OA. Biological analysis of PRP has demonstrated an anti-inflammatory effect on the intra-articular environment.

Purpose: To compare the clinical and biological effects of an intra-articular injection of PRP with those of an intra-articular injection of HA in patients with mild to moderate knee OA.

Study design: Randomized controlled trial; Level of evidence, 1.

Methods: A total of 111 patients with symptomatic unilateral knee OA received a series of either leukocyte-poor PRP or HA injections under ultrasound guidance. Clinical data were collected before treatment and at 4 time points across a 1-year period. Synovial fluid was also collected for analysis of proinflammatory and anti-inflammatory markers before treatment and at 12 and 24 weeks after treatment. Several measures were used to assess results: (1) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; (2) International Knee Documentation Committee (IKDC) subjective knee evaluation, visual analog scale (VAS) for pain, and Lysholm knee score; and (3) difference in intra-articular biochemical marker concentrations.

Results: There were 49 patients randomized to treatment with PRP and 50 randomized to treatment with HA. No difference was seen between the groups in the primary outcome measure (WOMAC pain score). In the secondary outcome measure, linear contrasts identified a significantly higher IKDC score in the PRP group compared with the HA group at 24 weeks (mean ± standard error [SE], 65.5 ± 3.6 vs 55.8 ± 3.8, respectively; P = .013) and at final follow-up (52 weeks) (57.6 ± 3.37 vs 46.6 ± 3.76, respectively; P = .003). Linear contrasts also identified a statistically lower VAS score in the PRP group versus the HA group at 24 weeks (mean ± SE, 34.6 ± 3.24 vs 48.6 ± 3.7, respectively; P = .0096) and 52 weeks (44 ± 4.6 vs 57.3 ± 3.8, respectively; P = .0039). An examination of fixed effects showed that patients with mild OA and a lower body mass index had a statistically significant improvement in outcomes. In the biochemical analysis, differences between groups approached significance for interleukin-1β (mean ± SE, 0.14 ± 0.05 pg/mL [PRP] vs 0.34 ± 0.16 pg/mL [HA]; P = .06) and tumor necrosis factor α (0.08 ± 0.01 pg/mL [PRP] vs 0.2 ± 0.18 pg/mL [HA]; P = .068) at 12-week follow-up.

Conclusion: We found no difference between HA and PRP at any time point in the primary outcome measure: the patient-reported WOMAC pain score. Significant improvements were seen in other patient-reported outcome measures, with results favoring PRP over HA. Preceding a significant difference in subjective outcomes favoring PRP, there was a trend toward a decrease in 2 proinflammatory cytokines, which suggest that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms. Registration: ClinicalTrials.gov (Identifier: NCT02588872).

Keywords: biomarkers; hyaluronic acid; inflammation; platelet-rich plasma.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Lysholm Knee Score
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / therapy*
  • Pain Measurement
  • Platelet-Rich Plasma* / metabolism
  • Prospective Studies
  • Synovial Fluid / drug effects
  • Synovial Fluid / metabolism*
  • Treatment Outcome


  • Hyaluronic Acid

Associated data

  • ClinicalTrials.gov/NCT02588872