Bisphosphonates (BP) are synthetic analogues of pyrophosphate, containing two carbon-phosphate bonds; such structure allows possible variations inducing different drug activity. BP are poorly absorbed in humans due to their low lipophilicity and to their high negative charge; in plasma they form complexes with proteins with a pH- and calcium-dependent binding. BP are rapidly cleared from blood since their rate of entry into bone is very fast; therefore, noncalcified tissues are exposed to the drug for only short periods. BP bind preferentially to bone with high turnover rate. Bone uptake seems to be affected by age, hypo- and hypercalcemia; thereafter they will be released only when the same skeletal segment will be again resorbed. BP both inhibit the mineralization process by a physicochemical effect and bone resorption by reducing the depth of the resorption sites. On the other hand osteoblastic activity doesn't appear to be reduced so that BP can induce a temporarily positive bone balance. The final target cell for BP anti- resorptive action is the osteoclast; however, such effect seems to be partly mediated though cells of the osteoblast-lineage. In fact, BP inhibit the production of some citokines participating in the differentiation of osteoclasts; furthermore, osteoclasts' adhesion to mineralized matrix appears to be reduced and their apoptosis anticipated. BP also act by modulating the release from osteoblasts of a factor which inhibits osteoclastic activity. BP are widely employed for treatment of osteoporosis; in this sense alendronate is now probably the most largely used bisphosphonate, since its effectiveness has been proved by several clinical trials. It both prevents the accelerated postmenopausal bone loss and it significantly reduces fracture incidence in osteoporotic patients. Risedronate and ibandronate are newer compounds currently under study.
|Number of pages||6|
|Journal||Italian Journal of Mineral and Electrolyte Metabolism|
|Publication status||Published - Mar 1999|
- Bone turnover
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