Objective To determine the short-term efficacy of oral glucosamine supplementation by evaluating structural lesions as assessed using 3T MRI Methods This was a randomized, double-blind placebo-controlled trial. Recruitment was via mass mailings and an arthritis registry in southwestern Pennsylvania. 201 participants with mild to moderate pain in one or both knees, as defined by Western Ontario and McMaster Universities (WOMAC) pain score ≥25 and ≤100, were enrolled. Of these, 69.2% had KL >= 2 in at least one knee. Participants had 24 weeks of treatment with 1500 mg glucosamine hydrochloride in beverage form or a placebo beverage. The primary outcome was decreased worsening of cartilage damage in all knees on 3T MRI, assessed according to a validated scoring system, WORMS(33). Secondary outcomes included change in bone marrow lesions (BMLs) in all knees and excretion of urinary CTX-II. Results The adjusted odds ratio (aOR) for decreased cartilage damage for any WORMS scored subregion in the glucosamine group compared to the control group was 0.938 (95% CI 0.528, 1.666). Compared to those treated, controls showed more improvement in BMLs (aOR=0.537; 95% CI 0.291, 0.990) but no difference in worsening BMLs (aOR = 0.691; 95% CI 0.410, 1.166). There was no indication that glucosamine decreased urine CTX-II excretion (beta = -0.10, 95% CI □0.21, 0.002). Conclusion: This short-term study provided no evidence of structural benefits (i.e., MRI morphology or urinary CTX-II excretion) from glucosamine supplementation in individuals with chronic knee pain. © 2013 American College of Rheumatology.