In multiple myeloma, the lytic bone lesions are caused primarily by:

• A Direct invasion of cortical bone by plasma cells
• B Plasma cell secretion of DKK1 and RANKL, increasing osteoclast activity while suppressing osteoblasts ✓
• C Increased PTHrP secretion causing systemic hypercalcemia without local lysis
• D Deposition of amyloid in bone marrow causing pressure necrosis

Explanation

Myeloma cells upregulate RANKL and secrete DKK1 (Dickkopf-1), which inhibits Wnt signaling in osteoblasts. The net result is increased osteoclastic bone resorption with suppressed bone formation, producing the characteristic 'punched-out' lytic lesions without reactive sclerosis. This differs from metastatic carcinoma where some reactive bone formation occurs.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.