Denosumab No Drug Holiday — SCE Rheumatology MCQ

Correct answer: A — No skeletal retention, so its effect wanes after a missed dose and rebound turnover can cause rapid bone loss and vertebral fractures

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

E is correct. Denosumab is a circulating anti-RANKL monoclonal antibody and does not accumulate in bone. Its antiresorptive effect therefore wanes when an injection is delayed or treatment is stopped, potentially producing rebound bone turnover, rapid loss of BMD and multiple vertebral fractures, often within 18 months. Denosumab should not be stopped without specialist review and a planned alternative antiresorptive strategy when cessation is necessary. In contrast, option A describes bisphosphonates, whose skeletal retention can provide residual activity during selected drug holidays. Denosumab does not produce irreversible osteoclast suppression (B), permanent RANKL downregulation (C), or a reliably gradual, risk-free return of bone turnover (D). Treatment duration should be reviewed individually after five years; continuation is not automatically indefinite.

Reference: Medicines and Healthcare products Regulatory Agency. Denosumab 60mg (Prolia): increased risk of multiple vertebral fractures after stopping or delaying ongoing treatment. Drug Safety Update, 2020. https://www.gov.uk/drug-safety-update/denosumab-60mg-prolia-increased-risk-of-multiple-vertebral-fractures-after-stopping-or-delaying-ongoing-treatment