[en] OBJECTIVE: To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in postmenopausal women with knee osteoarthritis (OA). DESIGN: This study consisted of a preplanned combination of two three-year, randomized, placebo-controlled, prospective, independent studies evaluating the effect of glucosamine sulfate on symptoms and structure modification in OA and post-hoc analysis of the results obtained in postmenopausal women with knee OA. Minimal joint space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were scored by the algo-functional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed in intention-to-treat, comparing joint space width and WOMAC changes between groups by ANOVA. RESULTS: Of 414 participants randomized in the two studies, 319 were postmenopausal women. At baseline, glucosamine sulfate and placebo groups were comparable for demographic and disease characteristics, both in the general population and in the postmenopausal women subset. After 3 years, postmenopausal participants in the glucosamine sulfate group showed no joint space narrowing [joint space change of +0.003 mm (95% CI, -0.09 to 0.11)], whereas participants in the placebo group experienced a narrowing of -0.33 mm (95% CI, -0.44 to -0.22; P < 0.0001 between the two groups). Percent changes after 3 years in the WOMAC index showed an improvement in the glucosamine sulfate group [-14.1% (95%, -22.2 to -5.9)] and a trend for worsening in the placebo group (5.4% (95% CI, -4.9 to 15.7) (P = 0.003 between the two groups). CONCLUSION: This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.