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Denosumab No Drug Holiday — SCE Rheumatology MCQ

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ModerateMetabolic Bone DiseaseDenosumab No Drug HolidaySCE Rheumatology

A 65-year-old woman with osteoporosis has received denosumab 60 mg subcutaneously every 6 months for 5 years. She asks whether she can now have a planned treatment-free interval, as may be considered after several years of bisphosphonate therapy. Which statement best explains why a routine denosumab drug holiday is generally inappropriate?

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Reveal the answer and explanation

Correct answer: A — Withdrawal rapidly reverses RANKL inhibition, causing rebound bone turnover, BMD loss and fracture risk

Explanation lettering: E = shown as A · A = shown as B · D = shown as C · C = shown as D · B = shown as E

Denosumab inhibits RANKL but, unlike bisphosphonates, is not retained within bone. As its concentration declines after a missed or final dose, osteoclast activity can rebound, with rapid loss of treatment-associated BMD and an increased risk of vertebral fractures, sometimes multiple. Therefore, a treatment-free drug holiday is inappropriate. Treatment should be reviewed individually after 5 years, but denosumab should either continue while clinically indicated or be stopped according to a planned sequential antiresorptive strategy, commonly involving a bisphosphonate around 6 months after the final injection. Options A and C describe the more persistent residual effect of bisphosphonates. Treatment does not permanently suppress osteoclasts after 5 years (B), and denosumab efficacy is not limited to one year (D).

Reference: Prolia 60 mg solution for injection, Summary of Product Characteristics, sections 4.2, 4.4 and 5.1, current 2026. https://www.medicines.org.uk/emc/product/568/smpc