Which mechanism best explains the purely osteolytic lesions seen in multiple myeloma?

• A Upregulation of RANKL by marrow stromal cells and osteoblasts, activating osteoclasts ✓
• B Increased secretion of osteoprotegerin by stromal cells
• C Direct resorption of bone by infiltrating plasma cells
• D Parathyroid hormone-driven stimulation of osteoclast precursors

Explanation

Myeloma cells secrete factors such as MIP-1 alpha and DKK1 that shift the RANKL to osteoprotegerin balance toward RANKL, driving osteoclast differentiation and focal lytic lesions without accompanying osteoblastic repair, which explains why bone scans are typically cold. Osteoprotegerin is a decoy receptor that inhibits osteoclasts, so its increase would protect bone. Plasma cells do not directly resorb bone, and parathyroid hormone is unrelated to this process.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.