A 65-year-old man has fatigue, bone pain, serum calcium 11.8 mg/dL, creatinine 2.4 mg/dL, and a monoclonal IgG spike on SPEP. Bone marrow biopsy shows 35% plasma cells. Osteolytic lesions are mediated primarily by which mechanism?

• A Direct bone destruction by plasma cell secreted matrix metalloproteinases
• B Increased RANK-L and decreased osteoprotegerin secreted by plasma cells and stromal cells, activating osteoclasts ✓
• C M-protein binding to osteocalcin and inhibiting osteoblast function
• D IL-6-mediated activation of RUNX2 in osteoblasts causing paradoxical bone resorption

Explanation

Myeloma plasma cells and bone marrow stromal cells secrete excess RANK-L (receptor activator of nuclear factor-kB ligand) and suppress osteoprotegerin (OPG, the decoy receptor that normally blocks RANK-L). This shifts the RANK-L:OPG ratio strongly in favor of osteoclast activation and bone resorption, producing the lytic lesions, hypercalcemia, and pain of myeloma 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.