A 70-year-old man has renal failure, hypercalcemia, and lytic bone lesions. Serum protein electrophoresis shows an M-spike in the gamma region. Which mechanism accounts for bone destruction in multiple myeloma?
- A Direct invasion by myeloma cells into cortical bone
- B Ectopic PTH secretion by myeloma cells causing generalized osteoclast activation
- C Myeloma cells secrete RANKL and DKK1, activating osteoclasts and inhibiting osteoblasts ✓
- D IL-6 directly dissolves hydroxyapatite crystals
Correct answer: C. Myeloma cells secrete RANKL and DKK1, activating osteoclasts and inhibiting osteoblasts
Explanation
Myeloma cells and stromal cells produce RANKL (receptor activator of NF-κB ligand) which drives osteoclast differentiation and activity, creating lytic lesions. Simultaneously, DKK1 (Dickkopf-1) secreted by myeloma cells inhibits the Wnt pathway, suppressing osteoblast activity and preventing bone repair. This uncoupling explains purely lytic lesions without reactive sclerosis. PTH is not secreted by myeloma cells.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.