Glucosamine for pain in osteoarthritis: Why do trial results differ?

Authors

  • Steven C. Vlad,

    Corresponding author
    1. Boston University Medical Center, Boston, Massachusetts
    • Boston University Medical Center, 715 Albany Street, Boston, Massachusetts 02118
    Search for more papers by this author
  • Michael P. LaValley,

    1. Boston University School of Public Health, Boston, Massachusetts
    Search for more papers by this author
    • Dr. LaValley has received an honorarium (less than $10,000) for serving as a member of a Data and Safety Monitoring Board for a GELITA Group study.

  • Timothy E. McAlindon,

    1. Tufts–New England Medical Center, Boston, Massachusetts
    Search for more papers by this author
    • Dr. McAlindon has received consulting fees (less than $10,000 each) from the GELITA Group, which manufactures a nutritional supplement for use in osteoarthritis, and from Source MDx.

  • David T. Felson

    1. Boston University Medical Center, Boston, Massachusetts
    Search for more papers by this author

Abstract

Objective

Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine.

Methods

We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double-blind, placebo-controlled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry-affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I2, a measure of heterogeneity.

Results

Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I2 was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47–0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest.

Conclusion

Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias.

Ancillary