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The pharmacology of bisphosphonates and new insights into their mechanisms of action
Author(s) -
Russell R. Graham G.,
Rogers Michael J.,
Frith Julie C.,
Luckman Steven P.,
Coxon Fraser P.,
Benford Helena L.,
Croucher Peter I.,
Shipman Claire,
Fleisch Herbert A.
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650140212
Subject(s) - bisphosphonate , chemistry , diphosphonates , mechanism of action , bone resorption , pharmacology , pyrophosphate , bone remodeling , biological activity , drug , metabolism , biochemistry , enzyme , osteoporosis , medicine , in vitro
Abstract Bisphosphonates are chemically stable analogs of inorganic pyrophosphate, which are resistant to breakdown by enzymatic hydrolysis. The biological effects of bisphosphonates on calcium metabolism were originally ascribed to their physico‐chemical effects on hydroxyapatite crystals. Although such effects may contribute to their overall action, their effects on cells are probably of greater importance, particularly for the more potent compounds. Remarkable progress has been made in increasing the potency of bisphosphonates as inhibitors of bone resorption, and the most potent compounds in current use are characterized by the presence of a nitrogen atom at critical positions in the side chain which, together with the bisphosphonate moiety itself, seems to be essential for maximal activity. As a class the bisphosphonates offer a very effective means of treating Paget's disease.