A postmenopausal woman with type 2 diabetes on pioglitazone sustains a vertebral fracture after minimal trauma. The increased fracture risk with thiazolidinediones is attributed to which mechanism?
- A Direct inhibition of intestinal calcium absorption
- B Activation of PPAR-gamma in mesenchymal stem cells diverting differentiation toward adipocytes rather than osteoblasts ✓
- C Suppression of parathyroid hormone secretion
- D Increased renal excretion of vitamin D metabolites
Correct answer: B. Activation of PPAR-gamma in mesenchymal stem cells diverting differentiation toward adipocytes rather than osteoblasts
Explanation
Thiazolidinediones activate PPAR-gamma in bone marrow mesenchymal stem cells, promoting adipogenesis over osteoblastogenesis, thereby reducing bone formation and increasing fracture risk, especially in postmenopausal women. Options A, C, and D are not mechanisms of thiazolidinedione-induced fractures.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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