Hyaluronic Acid Ineffective for Knee Osteoarthritis


Am Fam Physician. 2013 Feb 1;87(3):202-203.

Clinical Question

Is viscosupplementation with hyaluronic acid injection effective in decreasing pain in patients with knee osteoarthritis?

Bottom Line

Hyaluronic acid injection does not improve pain in patients with knee osteoarthritis but may result in serious adverse effects. (Level of Evidence = 1a–)


Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med.. 2012; 157( 3): 180– 191.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Foundation

Setting: Various (meta-analysis)


Hyaluronic acid is a naturally occurring substance that acts as a lubricant and shock absorber. Various injectable products are available—Synvisc, Orthovisc, Hyalgan, and others—for intra-articular treatment of knee pain caused by osteoarthritis. This systematic review, the latest of many trying to determine whether these products work, incorporated searches of several databases, including the Cochrane Register of Controlled Trials. The reviewers also searched conference proceedings and clinical trial registries to find unpublished data (which are more likely to have found no benefit compared with published research). Two authors independently evaluated the research for eligibility and extracted the data. They included randomized trials published in any language that evaluated any hyaluronic acid product against sham therapy or no treatment. The 89 studies, with a total of 12,667 patients, were evaluated for quality, which was generally low. This meta-analysis shows the importance of good systematic review technique, because there was significant heterogeneity among the studies and evidence of publication bias. The authors' analysis found that the lower the study quality, the larger the benefit. They also identified five unpublished studies, representing approximately 10 percent of the total number of patients, that found no benefit. In 18 large studies of high quality, hyaluronic acid produced no clinically relevant effect on knee pain (effect size = – 0.11; 95% confidence interval, – 0.18 to – 0.04). Fourteen studies found that treatment increased the risk of serious adverse effects (relative risk = 1.41; 95% confidence interval, 1.02 to 1.97).

EDITOR'S NOTE: In this issue, we resume publication of POEMs, patient-oriented evidence that matters. Many of you are already familiar with these short synopses of published research, or may remember our previous coverage of them from March 2003 through December 2006.1 Each month, a team—four family physicians, a clinical pharmacologist, and a hospitalist—scans more than 100 clinical journals looking for research articles that meet high standards for validity, relevance, and the potential to change practice. The team members select reports that involve outcomes that matter to patients, such as morbidity, mortality, quality of life, or cost. POEMs are peer reviewed by the academic fellowship faculty and fellows of the University of Missouri's Department of Family & Community Medicine. We think that POEMs will help busy physicians save time by highlighting studies that are most helpful to their practices.

Our POEMs series will be overseen by AFP's Deputy Editor for Evidence-Based Medicine, Dr. Mark Ebell, assisted by Associate Medical Editor Dr. Sumi Sexton. Dr. Ebell is a cofounder of POEMs, which is now part of Essential Evidence Plus, published by Wiley-Blackwell. Dr. Ebell also serves as editor-in-chief of Essential Evidence Plus.


1. Shaughnessy AF, Siwek J. Introducing POEMs. Am Fam Physician. 2003;67(6):1196–1199.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.



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