Mechanism of action: bisphosphonates bind hydroxyapatite in bone with high affinity and are taken up by osteoclasts during bone resorption; nitrogen-containing bisphosphonates inhibit farnesyl pyrophosphate synthase in the mevalonate pathway, disrupting osteoclast cytoskeletal function and inducing osteoclast apoptosis — reducing bone resorption and increasing net bone mineral density over time.
Uses: osteoporosis (postmenopausal and glucocorticoid-induced), Paget’s disease of bone, hypercalcemia of malignancy, bone metastases (reducing skeletal-related events).
Adverse effects: esophagitis/esophageal ulceration (oral agents — must be taken with water, upright, on an empty stomach), osteonecrosis of the jaw (rare, associated with dental procedures during therapy), atypical femoral fractures with long-term use, acute-phase reaction (fever, myalgia) after IV administration, hypocalcemia.
