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Calcium Homeostasis — MFDS Part 1 MCQ

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HardPhysiologyCalcium HomeostasisMFDS Part 1

A sustained increase in endogenous parathyroid hormone secretion occurs in response to a fall in plasma ionised calcium. Which downstream change would NOT contribute to restoration of the plasma ionised calcium concentration?

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Correct answer: B — Increasing osteoprotegerin expression by osteoblast-lineage cells, thereby suppressing osteoclastogenesis

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

A is correct. Osteoprotegerin is a decoy receptor for RANKL; increasing it suppresses osteoclast differentiation and bone resorption, so this would oppose the calcium-raising response. Sustained PTH instead increases the RANKL-to-osteoprotegerin ratio in osteoblast-lineage cells, indirectly promoting osteoclastogenesis and calcium release from bone (D). PTH also increases distal tubular calcium reabsorption (B), activates renal 1α-hydroxylase to increase calcitriol and intestinal calcium absorption (C), and decreases proximal tubular phosphate reabsorption (E). The resulting phosphaturia helps maintain ionised calcium by reducing phosphate available for calcium binding. Importantly, PTH primarily promotes osteoclast activity indirectly through osteoblasts and osteocytes rather than simply acting directly on osteoclasts.

Reference: Cartwright C et al. Hungry Bone Syndrome After Parathyroidectomy for Secondary Hyperparathyroidism: Pathogenesis and Contemporary Clinical Considerations, 2025. https://pubmed.ncbi.nlm.nih.gov/36894509/