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Healthou_Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled

O. Bruyere, Ph.D., Corresponding author contact information, E-mail the corresponding author, 

  • K. Pavelka, M.D., 
  • L.C. Rovati, M.D.§, 
  • J. Gatterová, M.D., 
  • G. Giacovelli,Ph.D.§, 
  • M. Olejarová, M.D., 
  • R. Deroisy, Ph.D., 
  • J.Y. Reginster, M.D.
    •  Department of Public Health, Epidemiology and Health Economics, University of Liege, Belgium
    •  Institute of Rheumatology, Prague, Czech Republic
    • § Clinical Pharmacology Department, Rotta Research Laboratorium-Rottapharm, Monza (MI), Italy



    To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo.


    Knee OA patients participating in two previous randomised, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement.


    Out of 340 patients with at least 12 months of treatment, 275 (i.e., 81%) could be retrieved and interviewed for the present evaluation: 131 formerly on placebo and 144 on glucosamine sulphate. There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation, making up a total of 2178 patient-years of observation (including treatment and follow-up).

    Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulphate, 9/144 (6.3%) (P = 0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% confidence interval (CI): 0.20–0.92), i.e., a 57% decrease compared with placebo. The Kaplan Meier/Log–Rank test survival analysis confirmed a significantly decreased (P = 0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate.

    A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up.


    Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation.

    Key words

    • Total joint replacement; 
    • Glucosamine sulphate; 
    • Epidemiology

    Figures and tables from this article:

    Full-size image (36 K)
    Fig. 1. 

    Patient disposition after the end of the original trial.

    Full-size image (17 K)
    Fig. 2. 

    Time-to-event analysis of total knee replacement in the overall follow-up population (N = 275): P = 0.026 (Log–Rank test).

    Table I.

    Baseline (pre-trial) demographic and clinical characteristics of the patients participating in the follow-up evaluation and of those lost to follow-up


    Data are mean (Standard Deviation).


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    Table II.

    Occurrence of total knee replacement during the follow-up, with Relative Risk of glucosamine sulphate vs placebo and P value


    The NNT with glucosamine sulphate to avoid one knee replacement is 12.


    View Within Article
    Table III.

    Mean (with standard error (SE) in brackets) use of health resources per patient in the year prior to the follow-up evaluation and total cost calculated for OA-related expenses. The data refer to a subset of 101 patients from Study 1 that attended the follow-up clinic visit

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    Corresponding author contact information


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