Clinical Question: Is intra-articular hyaluronic acid effective in the treatment of knee osteoarthritis?

Setting: Various (meta-analysis)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: Intra-articular hyaluronic acid for knee osteoarthritis is an expensive therapy that has been used widely since the U.S. Food and Drug Administration approved it in 1997. However, the efficacy of this procedure remains controversial. Two independent authors performed an extensive search for English- and non–English-language studies on MEDLINE and the Cochrane Controlled Trials Register, and in manuscript bibliographies and abstracts from scientific meetings.

They also attempted to include unpublished studies by contacting all authors to ask if they knew of any further trials. Only randomized trials with a minimum follow-up time of two months and dropout rate of less than 50 percent were included. Intention-to-treat analyses were used whenever possible.

Of 57 studies identified initially, 22 met the inclusion criteria. The overall dropout rate of these trials was 12.4 percent. In almost all of the trials, the 95 percent confidence intervals included an effect size of zero, consistent with no effect of the treatment. The results of two trials that evaluated the highest-molecular-weight hyaluronic acid found the greatest benefit of treatment and thus were heterogeneous (outliers) with the remaining studies. Analysis using a number of statistical tests found evidence of publication bias against negative trials (i.e., studies not finding benefit were less likely to be published, inflating the apparent benefit of the intervention).

Bottom Line: Intra-articular hyaluronic acid is minimally, if at all, more effective than placebo in the treatment of knee osteoarthritis. In this meta-analysis, the evidence of publication bias against negative trials suggests that any overall positive effect is overestimated. The highest-molecular-weight hyaluronic acid may be more effective than lower-molecular-weight hyaluronic acid. (Level of Evidence: 1a–)