The Effects of Pioglitazone on Bone Formation and Resorption Markers in Type 2 Diabetes Mellitus

OBJECTIVE: The use of thiazolidinediones is reported to be associated with an increased frequency of fractures, especially in women; however, the underlying mechanism is not clear. In this prospective study, we compared the effects of pioglitazone and metformin on bone metabolism in Japanese patients with type 2 diabetes mellitus. METHODS: A total of 58 patients with type 2 diabetes (24 men and 34 women) were randomly assigned to receive either pioglitazone (30 and 15 mg/day for men and women, respectively) or metformin (750 mg/day). The changes in serum and urinary type 1 cross-linked N-telopeptide (NTX), type 1 cross-linked C-telopeptide (CTX), bone alkaline phosphatase (BAP), homocysteine, and serum pentosidine were evaluated before and after three months of treatment. The primary endpoint was changes in bone resorption markers after three months. PATIENTS: The subjects of this research were male and female type 2 diabetes patients, less than 80 years of age. RESULTS: Pioglitazone significantly increased the serum and urinary NTX and serum and urinary CTX levels. The rates of changes in the serum and urinary NTX and CTX were significantly greater in the pioglitazone group than in the metformin group. Although the BAP levels decreased significantly in the pioglitazone group, the rates of change were similar between the two groups. In the pioglitazone group, the changes in fasting insulin levels correlated significantly with increased bone resorption, independent of age and gender. CONCLUSION: The results demonstrated that pioglitazone increased bone resorption independent of age and gender in Japanese patients with type 2 diabetes.