Clodronic acid
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Clodronic acid is a bisphosphonate used to treat osteoporosis in postmenopausal women, hypercalcemia of malignancy, and osteolysis.
Clodronic acid is a bisphosphonate used to treat osteoporosis in postmenopausal women, hypercalcemia of malignancy, and osteolysis.
Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. First generation bisphosphonates closely mimic the structure of pyrophosphate, which can be incorporated into ATP anologues that cannot be hydrolyzed, disrupting all ATP mediated actions of osteoclasts.
Clodronic acid is indicated as an adjunct in the management of osteolysis from bone metastases of malignant tumors and for management of hypercalcemia of malignancy.
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