alexa Bisphosphonates: a new class of drugs in diseases of bone and calcium metabolism.



Author(s): Fleisch H

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Abstract The geminal bisphosphonates are characterized by a PCP bond and are therefore analogs of pyrophosphate. They bind strongly to hydroxyapatite crystals and in vitro inhibit both crystal formation and dissolution. In vivo they inhibit soft tissue calcification and when given in large amounts also normal calcification. This effect is due to the inhibition of calcium phosphate crystal growth. Furthermore, the bisphosphonates are very potent inhibitors of bone resorption. The mechanism(s) of action is not yet known but is likely to be at a cellular level. The extent of the biological activity of each compound depends on the specific chemical structure, so that each individual bisphosphonate must be considered as a separate compound. The only common characteristic is the PCP group, which gives the compound its high affinity to bone. The individual effects, however, are determined by the side groups on the carbon atom. This opens interesting possibilities for the development of new compounds. No bisphosphonate analyzed so far can be degraded in vivo; all are either deposited in the skeleton, where they remain for years until the bone is destroyed, or are excreted in the urine. The high affinity for bone explains the specificity of the compounds for bone and the fact that they have relatively few nonosseous effects. Bisphosphonates are used in man to inhibit ectopic calcification, including dental tartar and ectopic ossification. Furthermore, they are used to inhibit bone resorption, especially in diseases such as Paget's disease and tumoral osteolysis. Finally, when linked to 99nTc, bisphosphonates are employed as bone scanning agents.
This article was published in Recent Results Cancer Res and referenced in Dentistry

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