Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro.

@article{Fisher1999AlendronateMO,
  title={Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro.},
  author={John E. Fisher and Michael J Rogers and J M Halasy and Steven P Luckman and David E Hughes and Pat Masarachia and G. Wesolowski and R. Graham G. Russell and Gideon A. Rodan and Alfred A. Reszka},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={1999},
  volume={96 1},
  pages={133-8}
}
Nitrogen-containing bisphosphonates were shown to cause macrophage apoptosis by inhibiting enzymes in the biosynthetic pathway leading from mevalonate to cholesterol. This study suggests that, in osteoclasts, geranylgeranyl diphosphate, the substrate for prenylation of most GTP binding proteins, is likely to be the crucial intermediate affected by these bisphosphonates. We report that murine osteoclast formation in culture is inhibited by both lovastatin, an inhibitor of hydroxymethylglutaryl… CONTINUE READING
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Fisher et al

  • M. J. Rogers, X. J. Xiong, +6 authors 625–630. 138 Cell Biology
  • Proc. Natl. Acad. Sci. USA 96
  • 1999
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