Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis

Arthritis Rheum. 2007 Dec 15;57(8):1410-8. doi: 10.1002/art.23103.


Objective: To compare the effectiveness and safety of intraarticular high-molecular hylan with standard preparations of hyaluronic acids in osteoarthritis of the knee.

Methods: We performed a systematic review and meta-analysis of randomized controlled trials comparing hylan with a hyaluronic acid in patients with knee osteoarthritis. Trials were identified by systematic searches of Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science Citation Index supplemented by hand searches of conference proceedings and reference lists (last update November 2006). Literature screening and data extraction were performed in duplicate. Effect sizes were calculated from differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled standard deviation. Trials were combined using random-effects meta-analysis.

Results: Thirteen trials with a pooled total of 2,085 patients contributed to the meta-analysis. The pooled effect size was -0.27 (95% confidence interval [95% CI] -0.55, 0.01), favoring hylan, but between-trial heterogeneity was high (I(2) = 88%). Trials with blinded patients, adequate concealment of allocation, and an intent-to-treat analysis had pooled effect sizes near null. The meta-analyses on safety revealed an increased risk associated with hylan for any local adverse events (relative risk [RR] 1.91; 95% CI 1.04, 3.49; I(2) = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I(2) = 0%).

Conclusion: Given the likely lack of a superior effectiveness of hylan over hyaluronic acids and the increased risk of local adverse events associated with hylan, we discourage the use of intraarticular hylan in patients with knee osteoarthritis in clinical research or practice.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / therapeutic use*
  • Aged
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / adverse effects
  • Biocompatible Materials / therapeutic use*
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / adverse effects
  • Hyaluronic Acid / analogs & derivatives*
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Biocompatible Materials
  • hylan
  • Hyaluronic Acid