A 64-year-old woman received denosumab 60 mg subcutaneously every 6 months for 4 years for osteoporosis. She then stopped attending follow-up and received no antiresorptive for 18 months. She now presents with two new vertebral compression fractures after minimal trauma. The mechanism responsible is:

• A Impaired osteoblast differentiation from persistent sclerostin elevation
• B Accumulation of microdamage from prolonged osteoclast suppression
• C Secondary hyperparathyroidism caused by impaired renal mineral handling
• D Rebound increase in osteoclastogenesis after loss of RANKL inhibition ✓

Explanation

Denosumab inhibits RANKL, blocking osteoclast formation. Its effect wanes within months of stopping because it does not bind bone, unlike bisphosphonates. Discontinuation produces a rebound rise in bone resorption markers above baseline, rapid BMD loss, and a cluster of multiple vertebral fractures. Microdamage accumulation explains atypical bisphosphonate fractures, not denosumab withdrawal, which kills option B. Patients stopping denosumab should be transitioned to a bisphosphonate.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.