A 55-year-old man presents with anemia, bone pain, and a monoclonal IgG kappa spike of 5 g/dL. Bone marrow shows 35% plasma cells. Serum calcium is 11.8 mg/dL. The mechanism of osteolytic lesions in multiple myeloma primarily involves:

• A Direct invasion of cortical bone by plasma cells secreting metalloproteinases
• B PTHrP secretion causing generalized bone resorption independent of RANK signalling
• C Myeloma immunoglobulin deposition in bone matrix triggering complement-mediated osteolysis
• D Myeloma cell production of RANKL and DKK-1 that activates osteoclasts and suppresses osteoblasts ✓

Explanation

In multiple myeloma, plasma cells produce RANKL (receptor activator of NF-kB ligand) and macrophage inflammatory protein-1alpha that activate osteoclasts, while simultaneously secreting Dickkopf-1 (DKK-1), a Wnt pathway inhibitor that suppresses osteoblast function. This uncoupling creates a net bone resorption state without compensatory new bone formation, generating the characteristic lytic 'punched-out' lesions without sclerotic margins seen on plain radiographs. PTHrP is characteristic of humoral hypercalcemia of malignancy (e.g., squamous 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.