Clodronate is a first generation non-nitrogenous bisphosphonate drug for the prevention and treatment of osteoporosis and skeletal fractures/hypercalcemia in patients with cancer. It strongly binds to hydroxyapatite and directly reduces osteoclast activity.1 Clodronate is metabolized in vitro to a cytotoxic ATP analog (AppCCl2p) which inhibits ADP/ATP translocase in the mitochondrial inner membrane leading to osteoclast apoptosis.2
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