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Denosumab Rebound — SCE Medical Oncology MCQ

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HardSupportive & Palliative OncologyDenosumab ReboundSCE Medical Oncology

A 72-year-old man with metastatic NSCLC and bone metastases is started on denosumab 120 mg monthly for prevention of skeletal-related events. After 18 months of denosumab, he develops severe hypercalcaemia 6 weeks after his last dose was missed. What phenomenon does this represent?

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Correct answer: B — Rebound hypercalcaemia after denosumab discontinuation

Rebound hypercalcaemia is a recognised phenomenon following denosumab discontinuation, occurring weeks to months after the last dose due to rapid increase in osteoclast-mediated bone resorption (RANKL 'overshoot'). It can be severe and potentially life-threatening. Management includes IV bisphosphonate (zoledronic acid) to suppress osteoclast activity, along with standard hypercalcaemia management. If denosumab is being discontinued, transitioning to a bisphosphonate can prevent rebound.

Reference: BNF Denosumab monograph; MHRA Drug Safety Update denosumab rebound; Bone et al JCO 2011