Alendronate reduces fracture risk in postmenopausal osteoporosis. At the molecular level, nitrogen-containing bisphosphonates act on osteoclasts by which mechanism?

• A Blocking the proton pump on the ruffled border membrane
• B Inhibiting farnesyl pyrophosphate synthase in the mevalonate pathway, leading to osteoclast apoptosis ✓
• C Acting as a decoy receptor for RANKL on osteoclast precursors
• D Stimulating caspase-independent necrosis through mitochondrial calcium overload

Explanation

Nitrogen-containing bisphosphonates bind hydroxyapatite, are internalized by osteoclasts, and inhibit farnesyl pyrophosphate synthase in the mevalonate pathway. This prevents prenylation of small GTPases essential for osteoclast survival and function, triggering apoptosis. Option C describes denosumab-like RANKL blockade, not bisphosphonates. Proton pump blockers such as proton pump inhibitors are not antiresorptives acting this way.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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