A 70-year-old woman with multiple myeloma develops bony pain and lytic lesions. The primary cytokine responsible for osteoclast activation in myeloma bone disease is:
- A RANKL (receptor activator of NF-κB ligand) ✓
- B IL-6
- C TNF-alpha
- D TGF-beta
Correct answer: A. RANKL (receptor activator of NF-κB ligand)
Explanation
In multiple myeloma, malignant plasma cells and bone marrow stromal cells upregulate RANKL while simultaneously suppressing its decoy receptor osteoprotegerin (OPG), tilting the RANKL:OPG ratio heavily toward osteoclast activation and bone resorption. This mechanism produces the characteristic lytic lesions, hypercalcaemia, and bone pain. IL-6 is a critical myeloma growth factor but is not the primary driver of osteoclast activation. TGF-beta released from resorbed bone further promotes myeloma growth.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.