title: Recent advances in understanding the mechanism of action of bisphosphonates.
abstract: Bisphosphonates (BPs) are widely used in the treatment of diseases associated with excessive osteoclast-mediated bone resorption, such as osteoporosis. Although several years ago the molecular target of the potent nitrogen-containing BPs (N-BPs) was identified as farnesyl diphosphate synthase, an enzyme in the mevalonate pathway, recent data have shed new light on the precise mechanism of inhibition and demonstrated that the acute-phase reaction, an adverse effect of N-BPs, is also caused by inhibition of this enzyme. In addition, the identification of BP analogues that inhibit different enzymes in the mevalonate pathway could lead to the development of novel inhibitors of bone resorption with potential applications in the treatment of bone disease.
authors.affiliation: Bone Research Group, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. f.p.coxon@abdn.ac.uk
authors.forename: Fraser P
authors.initials: FP
authors.lastname: Coxon
authors.forename: Keith
authors.initials: K
authors.lastname: Thompson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rogers
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000276:immunology; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051228:Geranyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
chemical_list: C410028:2-(3-pyridinyl)-1-hydroxyethylidene-1,1-phosphonocarboxylic acid; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004791:Enzyme Inhibitors; D011725:Pyridines; D051228:Geranyltranstransferase