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Myeloma Hypercalcaemia Mechanism — ESENeph MCQ

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ModerateElectrolyte DisordersMyeloma Hypercalcaemia MechanismESENeph

A 35-year-old man presents with a serum calcium of 3.5 mmol/L, PTH 0.3 pmol/L (suppressed), phosphate 0.8 mmol/L, and ALP 450 U/L. He has lytic bone lesions on skeletal survey. Serum protein electrophoresis shows an IgA lambda paraprotein. What is the mechanism of hypercalcaemia?

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Correct answer: A — Osteoclast-activating factors (RANKL, MIP-1alpha, IL-6) secreted by myeloma cells driving excessive bone resorption

Myeloma-associated hypercalcaemia is driven by local osteoclast-activating cytokines (RANKL, macrophage inflammatory protein-1alpha, IL-6, IL-3) secreted by myeloma cells in the bone marrow. These stimulate osteoclast activity and bone resorption, releasing calcium. PTH is appropriately suppressed by the hypercalcaemia. Treatment includes aggressive IV hydration, bisphosphonates (Zoledronic acid), and urgent chemotherapy to reduce the tumour burden. Denosumab (anti-RANKL) is an alternative to bisphosphonates.

Reference: NICE NG35 2016 – Myeloma; KDIGO 2012 – AKI