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 surfaces. The bisphosphonates also may inhibit resorption by inducing apoptosis of osteoclasts and by inhibiting release of interleukins and other compounds involved in bone resorption. The net result of actions of these compounds is inhibition of bone osteoclastic resorption. This action allows new bone formation to catch up in the remodeling process and can result in a net gain in bone density.


These hormones and drugs are used most commonly for disorders of calcium and bone metabolism rather than to correct specific hormone deficiencies. For example, the use of PTH replacement in hypoparathyroidism in the past was not practical because of the difficulty in ob-

taining purified hormone and the fact that it is injected subcutaneously. With the recent ability to produce large quantities of recombinant PTH (rPTH), its use will be more common, especially for severe osteoporosis.

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