Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee

J Rheumatol. 1999 Nov;26(11):2423-30.


Objective: Glucosamine products have been used extensively for the management of pain in osteoarthritis (OA). We investigated the efficacy of the hydrochloride salt of glucosamine on pain and disability in knee OA.

Methods: At Week -2, subjects were examined, randomized, and instructed to take only prescribed acetaminophen for pain. At Week 0 patients were examined, prescribed acetaminophen, and either placebo or glucosamine hydrochloride (glucosamine). At Week 4 the prescriptions for acetaminophen and placebo or glucosamine were renewed. At Weeks 4 and 8, patients returned diaries and unused medications, and were examined. The WOMAC questionnaire was administered at Weeks -2, 0, and 8. After completing the randomized 8 week trial, subjects were offered known glucosamine hydrochloride capsules in an 8 week open label trial, with followup telephone survey after the 8 week open label trial.

Results: The primary endpoint (statistically significant difference in WOMAC pain score between Week 0 and Week 8) was not met. However, positive trends were noted for the glucosamine group in 23 of 24 WOMAC questions. A significant difference was noted from Week 5 through Week 8 in the knee examination (p = 0.026) and in the response to a daily diary pain question (p = 0.018). However, responding to the question, "Are you better than at the start of the trial?", 40% of placebo and only 49% of glucosamine subjects answered in the affirmative (p = 0.58). At the end of the randomized trial, 34% of placebo and 47% of glucosamine subjects believed that they had been given glucosamine. After the end of the 8 week open label trial, 77% of the subjects were still taking glucosamine, although now obliged to pay for commercially available products.

Conclusion: There was no significant difference in pain reduction between the glucosamine hydrochloride and placebo groups as measured by WOMAC. However, the secondary endpoints of cumulative pain reduction as measured by daily diary and knee examination were favorable, suggesting that glucosamine hydrochloride benefits some patients with knee OA.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analgesics / administration & dosage
  • Analgesics / adverse effects
  • Analgesics / therapeutic use
  • Female
  • Glucosamine / administration & dosage
  • Glucosamine / adverse effects
  • Glucosamine / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / physiopathology
  • Pain / drug therapy*
  • Surveys and Questionnaires
  • Treatment Outcome


  • Analgesics
  • Glucosamine