A 70-year-old presents with bone pain, serum calcium 11.8 mg/dL, creatinine 2.4 mg/dL, and a monoclonal protein of 4.2 g/dL on SPEP. Bone marrow shows 35% plasma cells. The lytic bone lesions in multiple myeloma are primarily caused by:
- A RANK-L mediated osteoclast activation with simultaneous osteoblast inhibition ✓
- B Direct invasion by malignant plasma cells
- C PTHrP secretion causing systemic hypercalcemia
- D IL-6 driven osteocalcin suppression
Correct answer: A. RANK-L mediated osteoclast activation with simultaneous osteoblast inhibition
Explanation
Myeloma cells produce RANK-L (and suppress OPG), activating osteoclasts, while simultaneously producing DKK-1 and sclerostin to inhibit osteoblast function. This uncoupling of bone remodeling leads to pure lytic lesions without new bone formation, explaining the characteristic 'punched-out' lesions. PTHrP mediates humoral hypercalcemia of malignancy in solid tumors; IL-6 is a myeloma growth factor but does not primarily drive bone disease.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.