Denosumab, a fully human monoclonal antibody used for bone metastases and giant cell tumour of bone, acts by inhibiting which ligand-receptor interaction?

• A PTH binding to the PTH1 receptor on osteoblasts
• B OPG binding to RANKL on osteoblasts
• C Cathepsin K activation within the osteoclast ruffled border
• D RANK ligand binding to RANK on osteoclast precursors ✓

Explanation

Denosumab mimics osteoprotegerin by binding RANKL with high affinity, preventing RANKL from activating RANK on osteoclast precursors and mature osteoclasts. This arrests osteoclast differentiation, activation and survival, reducing bone resorption more completely than bisphosphonates. Cathepsin K is the target of odanacatib, an investigational agent never approved, and teriparatide stimulates rather than blocks the PTH1 receptor. Because it suppresses osteoclast activity profoundly, both hypocalcaemia and rebound hypercalcaemia after withdrawal are recognized complications.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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