Chapter: Modern Pharmacology with Clinical Applications: Parathyroid Hormone, Calcitonin, Vitamin D

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Bisphosphonates

The bisphosphonates are synthetic organic compounds that are incorporated directly into the hydroxyapatite of bone and then inhibit osteoclastic bone resorption.

BISPHOSPHONATES

 

The bisphosphonates are synthetic organic compounds that are incorporated directly into the hydroxyapatite of bone and then inhibit osteoclastic bone resorption. This antiresorptive action makes them useful in the pharmacological treatment of hypercalcemia, osteo-porosis, and Paget’s disease.

 

Chemistry

 

The bisphosphonates have a common structure, P-C-P, which is similar to the structure of the native pyrophos-phate P-O-P found in bone hydroxyapatite. The differ-ent compounds in clinical use vary by the attachments to the R component of the native molecule.

Mechanism of Action

 

The bisphosphonates inhibit osteoclastic resorption of bone by binding to the hydroxyapatite crystals of bone. When osteoclasts first attach to bone in the active resorp-tive sites, the bisphosphonates are released from that bone. The release of these compounds locally prevents further osteoclastic attachment to those resorptive sur-faces. The bisphosphonates also may inhibit resorption by inducing apoptosis of osteoclasts and by inhibiting release of interleukins and other compounds involved in bone re-sorption. The net result of actions of these compounds is inhibition of bone osteoclastic resorption. This action al-lows new bone formation to catch up in the remodeling process and can result in a net gain in bone density.

 

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