Effect of Glucosamine Sulfate on Hip Osteoarthritis: A Randomized Trial

BACKGROUND: The effectiveness of glucosamine sulfate for treating osteoarthritis is inconclusive.  Definitive evidence on the effectiveness of glucosamine sulfate is needed to assess its clinical usefulness.

OBJECTIVE: To evaluate the effect of glucosamine sulfate on the symptomatic and radiographic progression of hip osteoarthritis.

METHODS: This was a 2-year, double-blinded, randomized, placebo-controlled trial.  Patients were eligible if they met the American College of Rheumatology clinical criteria for hip osteoarthritis.  Patients were excluded from the study if they had undergone or were awaiting hip replacement surgery.  Patients were also excluded if they had a Kellgren and Lawrence score of 4, renal disease, liver disease, diabetes mellitus, or a disabling comorbid condition, as well as patients already receiving glucosamine.  Patients were randomly assigned to either 1500mg of oral glucosamine (administered once daily as two 750mg tablets) (n=111) or placebo (n=111) for 2 years.  The primary outcome measures were WOMAC 3.1 pain and function over 24 months and joint space narrowing after 24 months.  Secondary outcome measures were WOMAC pain, function, and stiffness after 3, 12, and 24 months; overall WOMAC stiffness; a visual analogue scale (VAS) to measure pain in the past week; and pain medication use.  The intention-to-treat method was used for analyzing the data.  The study needed to include 63 patients per group to detect a 0.25-mm difference in radiologic progression after 2 years between the glucosamine sulfate and placebo groups (power 80%).  Assuming 20% loss to follow-up, they needed 150 patients total.

RESULTS: There were 7 patients in the glucosamine group and 8 in the placebo group lost to follow-up.
In an adjusted analysis, the mean difference in WOMAC pain scores over 24 months was -1.54 (95% CI, -5.43 to 2.36).  The mean difference in WOMAC function scores were -2.01 (95% CI, -5.38 to 1.36).  The outcomes for joint space narrowing did not meet the minimal clinically important change o f 0.25 mm in either group.  In an adjusted analysis, small mean differences in WOMAC pain and function scores at 3, 12, and 24 months were found between glucosamine sulfate and placebo.  The overall difference in WOMAC stiffness score was -0.98 (CI, -4.99 to 3.04).  The mean difference in VAS was -2.04 (CI, -6.58 to 2.57).  There was no difference in pain medication use between the 2 groups; however use decreased in both groups after baseline.  The authors’ found no difference between glucosamine sulfate and placebo in modifying the symptomatic and radiographic progression of hip osteoarthritis over 24 months of daily therapy.

STRENGTHS: There were no apparent conflicts of interest in this study.  The rationale behind the study was appropriate due to inconclusive studies on the effects of glucosamine sulfate for hip osteoarthritis.  All those involved in the study were blinded to avoid bias.  The inclusion and exclusion criteria represented the population of interest.  Sensitivity analysis was performed to assess whether or not missing data would have made a difference in the results of the study.

LIMITATIONS: A study duration of 3 years would have been the optimal time period to assess joint space narrowing.  The data handling methods may have given inaccurate findings because patients who violated study protocol and those who had total hip arthroplasty during the study were encouraged to complete data collection to limit loss to follow-up.  Although the study looked at pain medication use during the study, they did not consider the type of medication used.  In addition, there were differences between groups in the amount of pain medication used at baseline.  The study used standard error of the mean instead of standard deviation.

CONCLUSION: Studies conducted over 3 years tend to show positive results in the efficacy of glucosamine sulfate.  If this study had been conducted over 3 years it may have shown a greater amount of joint space narrowing among patients.  Based on the limitations of this study, further study is needed to assess the clinical usefulness of glucosamine sulfate for hip osteoarthritis.  In future studies it would be important to conduct a longer study and to compare the use of pain medications in each group and also look at the types of pain medication used in each group. 

Rozendaal RM, Koes BW, van Osch GJ, Uitterlinden EJ, Garling EH, Willemsen SP, Ginai AZ, Verhaar JA, Weinans H, Bierma-Zeinstra SM.Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial. Ann Intern Med. 2008 Feb 19;148(4):268-77.

Michelle D. Kennedy, PharmD. Candidate