Bisphosphonates (BPs), also known as diphosphonates are class of drugs used for prevention and treatment of bone related disorders. They came into existence in 19th century and were primarily used as detergents, water softener, anticorrosive, and antiscaling agents (Russell, Watts, Ebetino, & Rogers, 2008). In 1960s, after understanding their properties and mechanism of action their use was determined in humans. BPs acted as antiresorptive agents with high affinity towards skeletal tissue. Their unique characteristics of controlling calcium and phosphate dissolution thereby preventing of loss of mineralized tissue attracted many industries and created potential market for their development. BPs were developed and used in the treatment of bone diseases such as Paget’s disease, multiple myeloma, hypercalcemia of malignancy, and osteoporosis.
Structure and mechanism of action:
BPs has a P-C-P backbone. They are synthetic analogs of inorganic pyrophosphate in which the oxygen is substituted by carbon. The R1 and R2 side-chains attached to the carbon atom are responsible for the large range of activity observed among the BPs. R1 enhances the binding to hydroxyapatite while R2 determines anti-resorptive properties and carbon enhances chemical stability and resistance to enzymatic degradation (Russell et al., 2008). Source: http://en.wikipedia.org/wiki/File:BisphosStruct.svg
There are 2 main types of BPs: nitrogen containing and non nitrogen containing. Depending on their type the mode of action differs. The nitrogen containing BPs are more potent and exert their action via inhibition of the mevalonate pathway which is by binding and blocki...
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...Watts, N. B., Ebetino, F. H., & Rogers, M. J. (2008). Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporosis International, 19(6), 733-759.
Schwartz, H. C. (2005). Bisphosphonate-associated osteonecrosis of the jaws. Journal of Oral and Maxillofacial Surgery, 63(10), 1555-1556.
Silverman, S. L., & Landesberg, R. (2009). Osteonecrosis of the jaw and the role of bisphosphonates: A critical review. The American Journal of Medicine, 122(2S), 33-45.
V.M. Cartsos, S. Zhu and A.I. Zavras,. (2008). Bisphosphonate use and the risk of adverse jaw outcomes: A medical claims study of 714,217 people. J Am Dent Assoc, 139, 23-30.
Woo, S. B., Hellstein, J. W., & Kalmar, J. R. (2006). Systematic review: Bisphosphonates and osteonecrosis of the jaws. Annals of Internal Medicine, 144(10), 753.
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