Intra-articular Hyaluronic Acid in Treatment of Knee Osteoarthritis: A Meta-analysis

CONTEXT Intra-articular hyaluronic acid is a US Food and Drug Administration–approved treatment for knee osteoarthritis (OA); however, its efficacy is controversial. OBJECTIVE To evaluate whether intra-articular hyaluronic acid is efficacious in treating knee OA. DATA SOURCES We searched for human clinical trials in MEDLINE (1966 through February 2003) and the Cochrane Controlled Trials Register, using the search terms (osteoarthritis, osteoarthrosis, or degenerative arthritis) and (hyaluronic acid, Hyalgan, Synvisc, Artzal, Suplasyn, BioHy, or Orthovisc). We also hand searched manuscript bibliographies that met inclusion criteria, selected rheumatic disease journals, and abstracts from scientific meetings. STUDY SELECTION Included were published or unpublished, English and non-English, single- or double-blinded, randomized controlled trials comparing intra-articular hyaluronic acid with intra-articular placebo injection for the treatment of knee OA. Trials also were required to have extractable data on pain reported by 1 of the outcome measures recommended by the Osteoarthritis Research Society. DATA EXTRACTION Two reviewers independently performed data extraction using standardized data forms. For each trial, we calculated an effect size (small-effect sizes, 0.2-0.5; large-effect sizes, 1.0-1.8, equivalent to a total knee replacement). We used a random-effects model to pool study results, the Cochrane Q test to evaluate heterogeneity, and a funnel plot and the Egger test to evaluate publication bias. DATA SYNTHESIS The overall dropout rate in the 22 selected trials was 12.4%. The pooled effect size for hyaluronic acid was 0.32 (95% confidence interval [CI], 0.17-0.47). There was significant heterogeneity among studies (P