COPYRIGHT © 2004 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED Therapeutic Effects of Hyaluronic Acid on Osteoarthritis of the Knee

Background: The magnitude of the therapeutic effects of intra-articular injection of hyaluronic acid on osteoarthritis of the knee is still in question. The aim of this meta-analysis was to elucidate the therapeutic efficacy and safety of intra-articular injection of hyaluronic acid for osteoarthritis of the knee. Methods: We conducted a meta-analysis of twenty blinded randomized controlled trials that compared the therapeu-tic effect of intra-articular injection of hyaluronic acid with that of intra-articular injection of a placebo to treat osteoar-thritis of the knee. The outcome end points were classified into three categories: pain with activities, pain without activities, and function. The outcome measures of the efficacy of hyaluronic acid were the mean differences in the ef-ficacy scores between the hyaluronic acid and placebo groups. The outcome measure of the safety of hyaluronic acid was the relative risk of adverse events. Results: Intra-articular injection of hyaluronic acid can decrease symptoms of osteoarthritis of the knee. We found significant improvements in pain and functional outcomes with few adverse events. However, there was significant be-tween-study heterogeneity in the estimates of the efficacy of hyaluronic acid. Subgroup analysis and meta-regression analysis showed that lower methodological quality such as a single-blind or single-center design resulted in higher es-timates of hyaluronic acid efficacy, that introduction of acetaminophen as an escape analgesic in the trial resulted in lower estimates of hyaluronic acid efficacy, and that patients older than sixty-five years of age and those with th