For patients with osteoarthritis (OA) of the knee, common, nonoperative therapies include nonsteroidal anti-inflammatory drugs, physical therapy, analgesics and intra-articular injections. Recommendations of the major medical societies, including the American Academy of Orthopedic Surgeons, the American College of Rheumatology and the American Medical Society for Sports Medicine, differ in their recommendations for the use of intra-articular hyaluronic acid. This meta-analysis was designed to better understand the effect of single versus multiple injections of hyaluronic acid for the treatment of OA of the knee.

A comprehensive literature search was conducted for articles assessing the efficacy of hyaluronic acid injections for patients with OA of the knee, with outcomes including pain, function and adverse events. Relevant articles were reviewed and included in the meta-analysis.

Studies included were 26, double-blind, randomized, controlled trials and four, single-blind, randomized, controlled trials involving a total of 5，848 patients. Low molecular weight hyaluronic acid was the most frequently used treatment (47%), followed by high molecular weight hyaluronic acid (43%) and moderate weight hyaluronic acid (10%). Compared with intra-articular saline, two to four injections of HA produced the largest reduction in pain at three (P<0.00001) and six (P＝0.008) months. Treatments involving five or more injections were correlated with significant improvement in pain at six months.

This meta-analysis of randomized, controlled trials involving hyaluronic acid for the treatment of osteoarthritis of the knee found that a series of two to four injections resulted in better outcomes than did single injections, or placebo.