What is the mechanism of action of bisphosphonates in osteoporosis treatment?

• A. Stimulate osteoclast activity
• B. Inhibit osteoblast activity
• C. Inhibit osteoclast activity
• D. Promote calcium resorption

Answer: (C)

Bisphosphonates act as antiresorptives by suppressing osteoclast activity and survival. They bind to bone surfaces, and when osteoclasts resorb bone, they take up the drug. Nitrogen-containing bisphosphonates inhibit the enzyme farnesyl pyrophosphate synthase in the mevalonate pathway, which prevents prenylation of small GTPase proteins required for osteoclast cytoskeletal organization, ruffled border formation, and survival. This leads to impaired resorption and osteoclast apoptosis, markedly reducing bone turnover. Some bisphosphonates also work through ATP-derived metabolites to reduce osteoclast activity. The net result is decreased bone resorption, stabilization or gain in bone density, and a lower fracture risk. They do not stimulate osteoblasts, nor promote calcium resorption; in fact, they help maintain calcium by reducing bone breakdown.