Bisphosphonates: mechanisms of action
Humans; Animals; Clodronate; Diphosphonates/chemistry/metabolism/pharmacology; Bone Development/drug effects; Bone Resorption/physiopathology
1998
Fleisch H
Endocrine Reviews
1998
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1210/er.19.1.80" target="_blank" rel="noreferrer">10.1210/er.19.1.80</a>
Bisphosphonate mechanism of action
Humans; Clodronate; Apoptosis; Bone Resorption/metabolism; Diphosphonates/chemistry/metabolism/pharmacology; Mevalonic Acid/antagonists & inhibitors; Osteoclasts/drug effects/metabolism/physiology; Osteoporosis/metabolism
The nitrogen-containing bisphosphonates (N-BPs), alendronate and risedronate, are the only pharmacologic agents shown to prevent spine and nonvertebral fractures associated with postmenopausal and glucocorticoid-induced osteoporosis. At the tissue level, this is achieved through osteoclast inhibition, which leads to reduced bone turnover, increased bone mass, and improved mineralization. The molecular targets of bisphosphonates (BPs) have recently been identified. This review will discuss the mechanism of action of BPs, focusing on alendronate and risedronate, which are the two agents most widely studied. They act on the cholesterol biosynthesis pathway enzyme, farnesyl diphosphate synthase. By inhibiting this enzyme in the osteoclast, they interfere with geranylgeranylation (attachment of the lipid to regulatory proteins), which causes osteoclast inactivation. This mechanism is responsible for N-BP suppression of osteoclastic bone resorption and reduction of bone turnover, which leads to fracture prevention.
2003
Reszka AA; Rodan GA
Current Rheumatology Reports
2003
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1007/s11926-003-0085-6" target="_blank" rel="noreferrer">10.1007/s11926-003-0085-6</a>