In multiple myeloma, hypercalcemia is primarily mediated through which mechanism?
- A Osteoclast activation via RANKL and DKK1 pathway producing osteolytic lesions ✓
- B Excess PTH secretion by plasma cells
- C Ectopic 1-alpha hydroxylation of vitamin D by tumor cells
- D Excess PTHrP secretion causing humoral hypercalcemia
Correct answer: A. Osteoclast activation via RANKL and DKK1 pathway producing osteolytic lesions
Explanation
In multiple myeloma, plasma cells secrete RANKL (and suppress OPG) along with DKK1 (inhibiting osteoblasts), resulting in uncoupled osteoclastic bone resorption without new bone formation — producing punched-out lytic lesions and hypercalcemia. PTH secretion is not a feature of myeloma. PTHrP is the mechanism in solid tumor hypercalcemia. Ectopic 1-alpha hydroxylation occurs in granulomatous diseases.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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