A 72-year-old man is found to have serum M-protein 3.8 g/dL (IgG kappa), bone marrow plasma cells 22%, lytic skull lesions, and calcium 11.6 mg/dL. The hypercalcemia in multiple myeloma is primarily driven by osteoclast activation mediated by which paracrine factor secreted by myeloma cells and their microenvironment?
- A Parathyroid hormone-related protein (PTHrP)
- B Interleukin-10 (IL-10)
- C RANKL (receptor activator of NF-κB ligand) ✓
- D Erythropoietin
Correct answer: C. RANKL (receptor activator of NF-κB ligand)
Explanation
In multiple myeloma, myeloma cells and marrow stromal cells produce excessive RANKL while simultaneously suppressing OPG (osteoprotegerin), the decoy receptor for RANKL. This imbalance activates osteoclasts, causing lytic bone lesions and hypercalcemia. PTHrP is the classic mediator of humoral hypercalcemia of malignancy in solid tumors (e.g., squamous cell carcinomas), not myeloma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.