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• W1855133612 abstract "Bisphosphonates are synthetic analogues of pyrophosphate, a naturally occurring substance which inhibits the mineralisation of bone. The therapeutic potential of these compounds, however, lies in their ability to inhibit bone resorption, and over the past two decades several bisphosphonates have been developed and evaluated in hyperresorptive states, particularly Paget's disease, hypercalcaemia of malignancy, and osteoporosis.1Bisphosphonates are characterised by two carbon-phosphorus bonds, the carbon atom replacing the oxygen in the P-O-P (phosphorus-oxygen- phosphorus) bond of pyrophosphate (fig 1) and the P-C-P (phosphorus carbon-phosphorus) bond conferring resistance to chemical and enzymatic hydrolysis. Different substitutions on the carbon atom have created several different bisphosphonates, each with its own individual pharmacological properties. The first bisphosphonate to be used therapeutically was etidronate, and subsequently many others have been developed. In order of increasing potency of antiresorptive activity the main bisphosphonates are etidronate, tiludronate, clodronate, pamidronate, alendronate, and risendronate.FIG 1 Chemical structure of pyrophosphate and three bisphosphonatesThe antiresorptive potency of the different compounds of bisphosphonate varies considerably. The antiresorptive effect is believed to be cell mediated but its mechanism has not been clearly established. Effects on osteoclast differentiation, recruitment, and activity have all been reported, and recent evidence suggests that effects on bone resorption are also mediated, at least in part, via osteoblastic cells.2,3 The considerable variations in antiresorptive potency between bisphosphonates may be attributable to different biochemical effects at the cellular level. The inhibitory effect is seen both for endogenous bone resorption and for resorption stimulated by agents such as parathyroid hormone, calcitriol, cytokines, and prostaglandins.Bisphosphonates have a strong affinity for hydroxyapatite crystals and in fairly high doses inhibit calcification of bone in vivo by physicochemical mechanisms. The ability to inhibit mineralisation varies considerably between bisphosphonates and is not related to antiresorptive potency.Bisphosphonates are not metabolised, and etidronate, …" @default.
• W1855133612 created "2016-06-24" @default.
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• W1855133612 date "1994-09-17" @default.
• W1855133612 modified "2023-10-17" @default.
• W1855133612 title "Fortnightly Review: The therapeutic use of bisphosphonates" @default.
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• W1855133612 doi "https://doi.org/10.1136/bmj.309.6956.711" @default.
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