Dr. Altman has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, QMed, Johnson & Johnson, PfizerTeva, DuPuy, and Iroko, and (more than $10,000 each) from Ferring and Oletec.
Osteoarthritis and Symptoms
Risk of Bias and Brand Explain the Observed Inconsistency in Trials on Glucosamine for Symptomatic Relief of Osteoarthritis: A Meta-Analysis of Placebo-Controlled Trials
Article first published online: 24 NOV 2014
Copyright © 2014 by the American College of Rheumatology
Arthritis Care & Research
Volume 66, Issue 12, pages 1844–1855, December 2014
How to Cite
Eriksen, P., Bartels, E. M., Altman, R. D., Bliddal, H., Juhl, C. and Christensen, R. (2014), Risk of Bias and Brand Explain the Observed Inconsistency in Trials on Glucosamine for Symptomatic Relief of Osteoarthritis: A Meta-Analysis of Placebo-Controlled Trials. Arthritis Care Res, 66: 1844–1855. doi: 10.1002/acr.22376
- Issue published online: 24 NOV 2014
- Article first published online: 24 NOV 2014
- Accepted manuscript online: 6 JUN 2014 09:09AM EST
- Manuscript Accepted: 27 MAY 2014
- Manuscript Received: 17 DEC 2013
- Oak Foundation
To determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trials of glucosamine's efficacy for treating pain in osteoarthritis (OA).
A systematic review and stratified meta-analysis of randomized placebo-controlled trials was performed, and random-effects models were applied with inconsistency (I2) and heterogeneity (tau2) estimated using Review Manager and SAS, respectively. The major outcome was reduction of pain; the standardized mean difference (SMD [95% confidence interval (95% CI)]) served as effect size.
The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine moderately reduced pain (SMD −0.51 [95% CI −0.72, −0.30]), although a high level of between-trial inconsistency was observed (I2= 88%). The single most important explanation (i.e., covariate) was brand, reducing heterogeneity by 41% (P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product resulted in significant pain reduction (SMD −1.07 [95% CI −1.47, −0.67]), although a sensitivity analysis of 3 low risk of bias trials using the Rottapharm/Madaus product showed less promising results (SMD −0.27 [95% CI −0.43, −0.12]), which is only a small effect size. Thirteen trials (1,963 patients) using non–Rottapharm/Madaus products consistently failed to show a reduction in pain (SMD −0.11 [95% CI −0.46, 0.24]). The second most important explanation was overall risk of bias (reducing heterogeneity by 32%).
Most of the observed heterogeneity in glucosamine trials is explained by brand. Trials using the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine. Large inconsistency was found, however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a small effect size.