Current Molecular Medicine

David W. Li  
College of Medicine
University of Nebraska Medical Center
Omaha, NE


Bisphosphonate Mechanism of Action

Author(s): Gideon A. Rodan, Alfred A. Reszka.


Nitrogen-containing bisphosphonates (N-BPs) are potent inhibitors of bone resorption widely used in the treatment of osteoporosis and other bone degrading disorders. At the tissue level, N-BPs reduce bone turnover, increase bone mass and mineralization, measured clinically as a rise in bone mineral density, increase bone strength and reduce fracture risk. At the cellular level, N-BPs, localize preferentially at sites of bone resorption, where mineral is exposed, are taken up by ostoclasts and inhibit osteoclast activity. The bone formation that follows incroporates the N-BP in the matrix, where it becomes pharmacologically inactive until released at a future time during bone remodeling. At the molecular level, N-BPs inhibit an enzyme in the cholesterol synthesis pathway, farnesyl diphosphate synthase. As a result, there is a reduction in the lipid geranylgeranyl diphosphate, which prenylates GTPases required for cytoskeletal organization and vesicular traffic in the osteoclast, leading to osteoclast inactivation.

Keywords: bisphosphonate, potent inhibitors, osteoporosis, mineralization, bone resorption, osteoclast activity, cholesterol synthesis, cytoskeletal organization, pharmacokinetics, cellular level

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

Year: 2002
Page: [571 - 577]
Pages: 7
DOI: 10.2174/1566524023362104
Price: $58