alexa Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy.
Biomedical Sciences

Biomedical Sciences

Journal of Biomedical Engineering and Medical Devices

Author(s): Li B, Ling Chau JF, Wang X, Leong WF

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Abstract Osteoporosis is a result of the disruption of bone homeostasis that is carried out by bone-forming osteoblasts and bone-degrading osteoclasts. The most common treatment of osteoporosis is N-containing bisphosphonates, a class of non-hydrolyzable pyrophosphate analogs. They have strong affinity to Ca(2+) of hydroxyapatite with high specificity and can only be liberated from the bone in an acidic environment. These properties bestow them unique pharmacokinetic features including specific and strong retention at bone resorption surface, uptaken specifically by osteoclasts, quick excretion of non-retained free bisphosphonates, long half-life, and recyclability. Such properties underlie the drugs' high efficacy, minor side effects, and intermittent dosing regimens. Further studies show that bisphosphonates inhibit farnesyl pyrophosphate synthase, a critical enzyme required for synthesis of isoprenyl and geranylgeranyl, and inhibit prenylation and geranylgeranylation of small G-proteins such as Rac and Rho. This leads to defective actin ring formation at the sealed zone, a subcellular structure essential for bone resorption, and a decrease in bone resorption. Bisphosphonates are also used to treat Paget's disease of bone, osteolytic bone metastases, and hypercalcemia. Moreover, these properties also make N-BPs a good candidate as a bone-seeking agent. Here we update our understanding of this remarkable class of anti-resorption drugs. Copyright © 2011 Wiley-Liss, Inc. This article was published in J Cell Biochem and referenced in Journal of Biomedical Engineering and Medical Devices

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