A 62-year-old postmenopausal woman with type 2 diabetes has been on pioglitazone for two years. She now presents with a low-trauma distal forearm fracture. Dual-energy X-ray absorptiometry shows reduced bone mineral density. Which class-related adverse effect best explains this event?
- A Thiazolidinediones inhibit intestinal calcium absorption via TRPV6 downregulation
- B Thiazolidinediones cause secondary hyperparathyroidism through vitamin D wasting
- C Thiazolidinediones increase osteoblast apoptosis and shift mesenchymal stem cell differentiation toward adipocytes ✓
- D Thiazolidinediones induce chronic metabolic acidosis buffering bone carbonate
Correct answer: C. Thiazolidinediones increase osteoblast apoptosis and shift mesenchymal stem cell differentiation toward adipocytes
Explanation
PPAR-gamma activation drives marrow mesenchymal stem cells toward adipocyte rather than osteoblast lineage and increases osteoblast apoptosis, reducing bone formation and density. This produces a recognized increased fracture risk in women, particularly postmenopausal, an FDA-labelled warning for pioglitazone and rosiglitazone. There is no significant effect on calcium absorption or parathyroid function, which eliminates options B and A.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.