Radiographs of a 65-year-old woman with multiple myeloma show purely lytic lesions without any sclerotic rim, and bone scan is falsely reassuring. Histology of a lesion shows brisk osteoclast resorption with complete absence of osteoblastic activity. Which paracrine change in the marrow microenvironment best explains this uncoupling?

• A Loss of calcitonin receptors on osteoclasts
• B Secretion of intact parathyroid hormone by neoplastic plasma cells
• C Direct resorption of mineralized matrix by plasma cells themselves
• D Increased RANKL expression with reduced osteoprotegerin production by stromal cells and osteoblasts ✓

Explanation

Myeloma cells induce marrow stromal cells and osteoblasts to upregulate RANKL while suppressing osteoprotegerin, the decoy receptor for RANKL. This tips the RANK-RANKL-OPG axis toward relentless osteoclast activation, and simultaneous suppression of osteoblast differentiation via Dickkopf-1 prevents bone repair, producing purely lytic lesions. Plasma cells do not secrete PTH, they cannot directly resorb bone, and calcitonin receptor loss is not part of the mechanism.

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.