Which hormone primarily increases osteoclast activity and promotes bone resorption via RANKL signaling?

• A. Calcitonin
• B. Vitamin D
• C. Estrogen
• D. Parathyroid hormone

Answer: (D)

Bone remodeling is controlled by signals that regulate osteoclast formation and activity through RANKL signaling. Parathyroid hormone is released when blood calcium is low and acts on osteoblasts to increase RANKL expression while reducing the decoy receptor osteoprotegerin. The higher RANKL/OPG ratio promotes binding to RANK on osteoclast precursors, driving their differentiation and activation, which leads to bone resorption and more calcium release into the blood. In contrast, calcitonin inhibits osteoclasts and reduces resorption; estrogen protects bone by dampening osteoclast activity; vitamin D mainly supports calcium absorption in the gut and, although it can influence RANKL under certain conditions, its primary role isn’t to drive RANKL-mediated bone resorption.