Bisphosphonates: Mechanisms of Action

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Bisphosphonates: mechanisms of action.

T bisphosphonates have been known to chemists since the middle of the 19th century, when the first synthesis occurred in 1865 in Germany (1). Etidronate, the first bisphosphonate to be used to treat a human disease (2), was synthesized exactly 100 yr ago (3). Bisphosphonates were used in industry, mainly as corrosion inhibitors or as complexing agents in the textile, fertilizer, and oil industr...

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Molecular mechanisms of action of bisphosphonates: current status.

PURPOSE Bisphosphonates are currently the most important class of antiresorptive agents used in the treatment of metabolic bone diseases, including tumor-associated osteolysis and hypercalcemia. These compounds have high affinity for calcium ions and therefore target bone mineral, where they are internalized by bone-resorbing osteoclasts and inhibit osteoclast function. EXPERIMENTAL DESIGN Th...

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Biochemical and molecular mechanisms of action of bisphosphonates.

This review describes the key discoveries over the last 15 years that have led to a clearer understanding of the molecular mechanisms by which bisphosphonate drugs inhibit bone resorption. Once released from bone mineral surfaces during bone resorption, these agents accumulate intracellularly in osteoclasts. Simple bisphosphonates such as clodronate are incorporated into non-hydrolysable analog...

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Denosumab and bisphosphonates: different mechanisms of action and effects.

To treat systemic bone loss as in osteoporosis and/or focal osteolysis as in rheumatoid arthritis or periodontal disease, most approaches target the osteoclasts, the cells that resorb bone. Bisphosphonates are currently the most widely used antiresorptive therapies. They act by binding the mineral component of bone and interfere with the action of osteoclasts. The nitrogen-containing bisphospho...

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Bisphosphonates: Mode of Action and Pharmacology

The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in...

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ژورنال

عنوان ژورنال: Endocrine Reviews

سال: 1998

ISSN: 0163-769X

DOI: 10.1210/er.19.1.80