Clodronic Acid
Clodronic Acid is a first-generation bisphosphonate with anti-resorptive and anti-hypercalcemic activities. Clodronic acid adsorbs onto the surface of the hydroxyapatite crystals in bone matrix. Although the exact mechanism through which clodronic acid exerts its cytotoxic effect on osteoclasts has yet to be fully elucidated, this agent is metabolized intracellularly to a toxic beta-gamma-methylene analog of adenosine triphosphate (ATP), AppCCl2p. The ATP analog AppCCl2p competitively inhibits ADP/ATP translocase, thereby interfering with mitochondrial membrane potential and cellular energy metabolism. This may cause osteoclast apoptosis and, eventually, inhibiting osteoclast-mediated bone resorption.