Orthopedics · Metabolic Bone Diseases (Osteoporosis, Osteomalacia, Paget's)

A 70-year-old postmenopausal woman has a T-score of −2.7 at the hip with a 10-year FRAX major osteoporotic fracture probability of 18%. She had a previous fragility wrist fracture. Pharmacological treatment is initiated. Which drug has a DUAL mechanism of both inhibiting bone resorption AND stimulating bone formation?

  • A Romosozumab (anti-sclerostin monoclonal antibody)
  • B Alendronate (bisphosphonate)
  • C Denosumab (RANKL inhibitor)
  • D Teriparatide (PTH analogue)
Correct answer: A. Romosozumab (anti-sclerostin monoclonal antibody)

Explanation

Romosozumab is a monoclonal antibody against sclerostin (a Wnt pathway inhibitor secreted by osteocytes). By blocking sclerostin, romosozumab disinhibits Wnt signalling, stimulating osteoblast activity and bone formation. Simultaneously, it reduces RANKL expression, suppressing osteoclast-mediated bone resorption. This dual anabolic-antiresorptive mechanism produces the largest BMD increases of any approved agent. Alendronate and denosumab are purely antiresorptive. Teriparatide is primarily anabolic (stimulates bone formation via PTH1R), with some secondary resorption increase — it is not dual-mechanism. Romosozumab is approved for severe postmenopausal osteoporosis with high fracture risk.

Reference: Maheshwari Essential Orthopaedics, 6th ed.

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