Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review and Meta-analysis.

: Background: Viscosupplementation, the intra-articular injection of hyaluronic acid, is widely used for symptomatic knee osteoarthritis. Purpose: To assess the benefits and risks of viscosupplementation for adults with symptomatic knee osteoarthritis. Data Sources: MEDLINE (1966 to January 2012), EMBASE (1980 to January 2012), the Cochrane Central Register of Controlled Trials (1970 to January 2012), and other sources. Study Selection: Randomized trials in any language that compared viscosupplementation with sham or nonintervention control in adults with knee osteoarthritis. Data Extraction: Primary outcomes were pain intensity and flare-ups. Secondary outcomes included function and serious adverse events. Reviewers used duplicate abstractions, assessed study quality, pooled data using a random-effects model, examined funnel plots, and explored heterogeneity using meta-regression. Data Synthesis: Eighty-nine trials involving 12 667 adults met inclusion criteria. Sixty-eight had a sham control, 40 had a follow-up duration greater than 3 months, and 22 used cross-linked forms of hyaluronic acid. Overall, 71 trials (9617 patients) showed that viscosupplementation moderately reduced pain (effect size, -0.37 [95% CI, -0.46 to -0.28]). There was important between-trial heterogeneity and an asymmetrical funnel plot: Trial size, blinded outcome assessment, and publication status were associated with effect size. Five unpublished trials (1149 patients) showed an effect size of -0.03 (CI, -0.14 to 0.09). Eighteen large trials with blinded outcome assessment (5094 patients) showed a clinically irrelevant effect size of -0.11 (CI, -0.18 to -0.04). Six trials (811 patients) showed that viscosupplementation increased, although not statistically significantly, the risk for flare-ups (relative risk, 1.51 [CI, 0.84 to 2.72]). Fourteen trials (3667 patients) showed that viscosupplementation increased the risk for serious adverse events (relative risk, 1.41 [CI, 1.02 to 1.97]). Limitations: Trial quality was generally low. Safety data were often not reported. Conclusion: In patients with knee osteoarthritis, viscosupplementation is associated with a small and clinically irrelevant benefit and an increased risk for serious adverse events. Primary Funding Source: Arco Foundation.