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Denosumab Discontinuation Rebound — SCE Rheumatology MCQ

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HardMetabolic Bone DiseaseDenosumab Discontinuation ReboundSCE Rheumatology

A 70-year-old woman has received denosumab 60 mg every 6 months for osteoporosis for 6 years. Because of a prolonged supply interruption, her next dose cannot be administered; her last injection was 7 months ago. Her corrected calcium is normal and her eGFR is 68 mL/min/1.73 m². Which statement best describes the principal concern and appropriate response?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: D — Rebound osteoclast activity can rapidly reverse BMD gains and cause multiple vertebral fractures; if denosumab cannot be given promptly, specialist-directed bisphosphonate therapy is needed.

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

D is correct. Unlike bisphosphonates, denosumab is not retained in bone. When RANKL inhibition wanes, bone turnover can rebound above pretreatment levels, rapidly reversing BMD gains and precipitating multiple vertebral fractures. At 7 months she is already beyond the scheduled dosing interval; the MHRA has reported fractures within the first 9 months and up to 18 months after stopping or delaying treatment. Denosumab should be administered as soon as possible if it becomes available. If discontinuation is unavoidable, urgent specialist-directed sequential antiresorptive treatment, usually a bisphosphonate, is required. A and C incorrectly assume persistent protection or that the risk period has passed. Teriparatide alone does not suppress rebound resorption, excluding B. Hypocalcaemia is principally an adverse effect after administration in susceptible patients; calcium and vitamin D alone do not prevent withdrawal-associated fractures, excluding E.

Reference: European Calcified Tissue Society: Tsourdi E et al. Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. Journal of Clinical Endocrinology & Metabolism, 2020. https://pubmed.ncbi.nlm.nih.gov/33103722/