Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women

Objectives: Our objectives were to evaluate the effect of rosiglitazone on bone metabolism and to assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women. Design: This was a 12-wk open-label randomized-controlled trial. Patients or Other Participants: A total of 56 obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index were included in the study. Interventions: 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 Measures: Before and after the interventions, metabolic bone markers and serum cytokine levels were assessed. Results: Serum total alkaline phosphatase ( ALP) and bone-specific ALP levels were statistically significantly lower 12 wk after initiation of rosiglitazone treatment. There were no statistically significant changes in osteocalcin levels among the three groups or in deoxypyridinoline levels in the rosiglitazone group. At the end of 12 wk, all patients had statistically significantly decreased IL-1 beta and TNF-alpha levels compared with baseline. Changes in bone-specific ALP 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.