Bisphosphonate Mechanism — MFDS Part 1 MCQ
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Correct answer: D — Adsorption to mineralised bone, uptake by osteoclasts during resorption, and inhibition of farnesyl pyrophosphate synthase
Explanation lettering: B = shown as A · E = shown as B · A = shown as D · D = shown as E
A is correct. Zoledronic acid has a high affinity for mineralised bone and is taken up by osteoclasts at sites of active resorption. It inhibits farnesyl pyrophosphate synthase in the mevalonate pathway, reducing the isoprenoid intermediates required for protein prenylation and thereby impairing osteoclast function and survival. It does not directly stimulate osteoblasts or activate alkaline phosphatase (B). Although acidification of the resorption lacuna is essential, carbonic anhydrase II is not zoledronic acid's molecular target (C). RANKL regulates osteoclast differentiation, but its suppression is not the principal mechanism of zoledronic acid (D). The drug does not act through systemic calcium chelation or calcitonin release (E). Non-nitrogen-containing bisphosphonates instead form cytotoxic ATP analogues.
Reference: Electronic Medicines Compendium, Aclasta 5 mg solution for infusion, Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, updated 19 June 2026. https://www.medicines.org.uk/emc/product/210/smpc