## Calcium Metabolism in Multiple Myeloma **Key Point:** Hypercalcemia in myeloma arises from two mechanisms: (1) osteoclastic bone resorption driven by RANKL and other cytokines, and (2) impaired renal excretion due to light-chain nephropathy. Myeloma cells do NOT produce calcitriol (active vitamin D) — this is a feature of granulomatous diseases (sarcoidosis, tuberculosis) and lymphomas, not myeloma. ### Mechanisms of Hypercalcemia in Myeloma | Mechanism | Pathophysiology | Frequency | | --- | --- | --- | | Osteoclastic resorption | RANKL, TNF-α, IL-6 from myeloma cells stimulate osteoclasts | Most common | | Impaired renal excretion | Light-chain cast nephropathy reduces GFR and calcium clearance | Common | | PTHrP secretion | Rare in myeloma (more common in solid tumors) | Uncommon | | Calcitriol production | NOT a feature of myeloma | Does not occur | **High-Yield:** The distinction between myeloma-induced and granulomatous hypercalcemia is testable. Myeloma causes hypercalcemia through bone resorption and renal dysfunction, NOT through vitamin D activation. **Clinical Pearl:** When evaluating hypercalcemia in a myeloma patient, check 1,25-dihydroxyvitamin D levels — they should be suppressed (low), not elevated. An elevated level suggests an alternative diagnosis (sarcoidosis, lymphoma). ### Why Option 3 is Correct Myeloma cells lack the enzymatic machinery (1α-hydroxylase) to convert 25-hydroxyvitamin D to the active 1,25-dihydroxyvitamin D form. This is a defining feature of granulomatous and lymphoproliferative diseases, not myeloma.
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