A 68-year-old woman with multiple myeloma has severe vertebral compression fractures. Serum alkaline phosphatase is within normal limits despite extensive osteolytic lesions on imaging. Which mechanism best explains the lytic lesions and this laboratory finding?
- A Osteoblast activation with compensatory osteoclast suppression by tumor-derived cytokines
- B Secondary hyperparathyroidism from renal failure causing generalized bone resorption
- C Direct metastatic destruction of trabecular bone by infiltrating plasma cells alone
- D Osteoclast activation driven by RANK ligand and myeloma-derived factors with absent osteoblastic repair ✓
Explanation
Myeloma bone disease results from uncoupled remodeling: myeloma cells induce RANKL expression on stromal cells and osteoblasts and secrete osteoclast-activating factors such as MIP1-alpha, driving marked osteoclastic resorption, while Wnt antagonists like DKK1 suppress osteoblast activity. Because there is essentially no compensatory osteoblastic new bone formation, serum alkaline phosphatase remains normal despite extensive lysis, a feature distinguishing myeloma from osteoblastic metastases. Direct plasma cell invasion alone does not account for the osteoclast-driven resorption.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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