A 68-year-old man has bone pain, serum calcium 12.5 mg/dL, creatinine 2.8 mg/dL, Hb 9 g/dL, and rouleaux formation on peripheral smear. Bone marrow biopsy shows 45% plasma cells. Skeletal survey shows multiple 'punched-out' lytic lesions. The mechanism responsible for hypercalcemia in this condition is primarily:
- A Osteoclast activation via RANKL/OPG imbalance driven by myeloma cells and marrow stromal cells ✓
- B Ectopic PTH secretion by plasma cells
- C Decreased renal calcium excretion due to tubular involvement by light chains
- D Granulomatous conversion of vitamin D to 1,25-dihydroxyvitamin D by plasma cells
Correct answer: A. Osteoclast activation via RANKL/OPG imbalance driven by myeloma cells and marrow stromal cells
Explanation
In multiple myeloma, hypercalcemia results from myeloma cell-induced osteoclast activation. Myeloma cells and surrounding stromal cells produce RANKL, DKK-1, MIP-1α, and IL-3/IL-6, which activate osteoclasts while suppressing osteoblasts (via DKK-1 inhibition of Wnt signaling), creating pure lytic lesions. Ectopic PTH is not produced by myeloma cells; granulomatous 1,25-OH2D production is characteristic of sarcoidosis; light chain nephropathy impairs calcium excretion but is not the primary mechanism.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.