A 63-year-old postmenopausal woman started on adjuvant anastrozole for ER-positive breast cancer returns after 18 months with a low-trauma vertebral compression fracture. DEXA shows a T-score of minus 3.0. Which mechanism explains her bone loss and what is the appropriate intervention?
- A Aromatase inhibition abolishing residual peripheral oestrogen synthesis, accelerating bone resorption; give bisphosphonates with vitamin D and calcium ✓
- B Tamoxifen agonist action on bone; stop endocrine therapy entirely
- C Direct toxic effect of anastrozole on osteoblasts; substitute exemestane which is bone neutral
- D Secondary hyperparathyroidism from anastrozole; start cinacalcet
Correct answer: A. Aromatase inhibition abolishing residual peripheral oestrogen synthesis, accelerating bone resorption; give bisphosphonates with vitamin D and calcium
Explanation
Aromatase inhibitors block conversion of adrenal androgens to oestradiol in peripheral fat, dropping postmenopausal oestrogen to near zero and accelerating osteoclast-mediated resorption, unlike tamoxifen which protects bone in postmenopausal women. Management includes calcium, vitamin D, weight-bearing exercise, and bisphosphonates or denosumab when T-score falls below minus 2.5 or fragility fracture occurs. Exemestane, a steroidal inactivator, also reduces bone density, so switching does not solve the problem.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.