A 62-year-old man with newly diagnosed multiple myeloma is being counseled about his disease. Which of the following is NOT a typical feature of multiple myeloma?

Question

Accepted Answer

B. Hypercalcemia from increased intestinal absorption of calcium via active vitamin D synthesis by myeloma cells. ## 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.

Answer

A. Lytic bone lesions due to increased osteoclast activity mediated by RANKL

Answer

C. Anemia primarily due to marrow infiltration by plasma cells and EPO suppression

Answer

D. Hypercalcemia from osteoclastic bone resorption and increased renal reabsorption of calcium

A 62-year-old man with newly diagnosed multiple myeloma is being counseled about his disease. Which of the following is NOT a typical feature of multiple myeloma?

Explanation

Calcium Metabolism in Multiple Myeloma

Mechanisms of Hypercalcemia in Myeloma

Why Option 3 is Correct

Practice similar questions

Join our NEET PG community

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