A 70-year-old woman with type 2 diabetes on pioglitazone for 3 years presents with a fragility fracture of the distal forearm. Pioglitazone increases fracture risk in postmenopausal women primarily through which mechanism?

• A Direct osteoclast activation via RANKL upregulation
• B Inhibition of intestinal calcium absorption
• C Increased renal phosphate excretion causing osteomalacia
• D PPAR-gamma mediated diversion of mesenchymal stem cells away from osteoblasts toward adipocytes ✓

Explanation

Pioglitazone activates PPAR-gamma on mesenchymal stem cells in bone marrow, promoting differentiation into adipocytes rather than osteoblasts. This reduces bone formation over time and increases fracture risk, especially in postmenopausal women who already have increased bone resorption. The effect is distinct from antiresorptive mechanisms like RANKL activation.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.