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A Prospective, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy of Intraarticular Hyaluronic Acid for Osteoarthritis of the Knee



Objective. To assess the efficacy of intraarticular (IA) injections of hyaluronic acid (HA) compared to placebo in patients with osteoarthritis (OA) of the knee; and to assess patient satisfaction with treatment relative to placebo, and whether there is a difference between a series of 3 versus 6 consecutive IA injections.

Methods. We conducted a randomized, double-blind, placebo controlled, 2-arm parallel design trial of 106 patients with radiologically confirmed knee OA. Two-milliliter IA injections using 20 mg/ml HA sodium salt or saline placebo were administered once weekly over 3 weeks (HA and placebo groups), followed by once weekly IA injection with 2.0 ml (20 mg/ml) HA for a further 3 consecutive weeks. The primary efficacy assessment included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score for knee pain (Week 3 score). Secondary efficacy assessments included WOMAC scores for knee pain at Weeks 6 and 12 (followup), as well as WOMAC stiffness, physical function and quality of life scores, visual analog scale (VAS) scores for pain at rest and following walking and stepping activity, range of knee joint motion, and global patient satisfaction with treatment and quality of life using the SF-36.

Results. After 3 weeks of study treatment, both treatment groups showed improvements in knee function, the HA group showing a greater improvement compared to placebo in WOMAC knee pain score (p < 0.01). The HA group showed greater (p < 0.05) improvement in the overall WOMAC score and VAS pain following walking and stepping activity at Week 3. Results from all other secondary efficacy assessments at Weeks 6 and 12 including patient satisfaction were similar and were not statistically significant between treatment groups, and there were no significant differences between groups for adverse events.

Conclusion. Intraarticular HA was superior to placebo in improving knee pain and function, with no difference between 3 or 6 consecutive injections for the primary efficacy assessment. (J Rheumatol 2006;33:951-6)

Key Indexing Terms:


From the Departments of Family Medicine and Physical Medicine and Rehabilitation, Schulich School of Medicine and School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, Ontario, Canada.

Supported by a grant from Bioniche Life Sciences, Belleville, Ontario, Canada. R.J. Petrella is supported by a Canadian Institutes of Health Research Investigator Award in Healthy Aging.

R.J. Petrella, MD, PhD; M. Petrella, PhD.

Address reprint requests to Dr. R.J. Petrella, Heart Health and Exercise Laboratory, 1490 Richmond Street, London, Ontario N6G 2M3. E-mail:

Accepted for publication December 13, 2005.

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© 2006. The Journal of Rheumatology Publishing Company Limited.
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