Rosiglitazone Decreases Serum Bone-Specific Alkaline Phosphatase Activity in Postmenopausal Diabetic Women.

Author(s): Berberoglu Z, Gursoy A, Bayraktar N, Yazici AC, Tutuncu NB, Demirag NG

Affiliation(s): Departments of Endocrinology and Metabolism, Biochemistry, and Biostatistics, Baskent University Faculty of Medicine, Ankara, Turkey.

Publication date & source: 2007-06-26, J Clin Endocrinol Metab., [Epub ahead of print]

Publication type:

Objective: To evaluate the effect of rosiglitazone on bone metabolism and assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women. Design Twelve-week open-label randomized controlled trial. Patients or Other Participants: Fifty-six obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index. Intervention(s): The subjects were instructed to follow a weight-maintenance diet. Half were randomly assigned to receive rosiglitazone 4 mg/d, and the other half remained on diet alone. Main Outcome Measure(s): Before and after the interventions, metabolic bone markers and serum cytokine levels were assessed. Results: Serum total alkaline phosphatase and bone-specific alkaline phosphatase (bsALP) levels were statistically significantly lower 12 weeks after the initiation of rosiglitazone treatment. There were no statistically significant changes in osteocalcin levels among the 3 groups or in deoxypyridinoline levels in the rosiglitazone group. At the end of 12 weeks, all patients had statistically significantly decreased interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) levels compared with baseline. Changes in bsALP levels showed a moderate negative correlation with the changes in the TNF-alpha levels after rosiglitazone treatment and after diet in the diabetic control group. Conclusions: Rosiglitazone use is associated with reduced bone formation at earlier stages in postmenopausal diabetic women. The cytokine-lowering effects of rosiglitazone and lifestyle changes could reverse the early inhibitory effect of rosiglitazone therapy on bone formation. Further studies will clarify the long-term effects of rosiglitazone therapy on bone loss and fracture.