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Best Pract Res Clin Endocrinol Metab. 2008 Oct;22(5):831-47. doi: 10.1016/j.beem.2008.07.001.

Bisphosphonates: how do they work?

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Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands.


Bisphosphonates (BPs) are taken up preferentially by the skeleton and decrease osteoclast-mediated bone resorption. The capacity of the skeleton to retain BPs is large, and there is no indication for saturation of binding sites with the doses used in osteoporosis. The anti-resorptive action of BPs includes their selective binding to calcium crystals and their subsequent release and uptake by the osteoclasts. There are differences in the affinities of PBs for bone as well as in their anti-resorptive potencies, and the whole molecule is responsible for their inhibitory effect on bone resorption. At the tissue level, they decrease the rate of bone resorption and turnover, increase bone mineral density, and maintain or improve structural and material properties of bone and thereby reduce the risk of fractures. Current studies address questions related primarily to the pharmacological properties of these compounds that are essential for their optimal clinical use, such as for example long-term safety and efficacy.

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