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Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy
Each bisphosphonates has a unique profile that may help to explain potential clinical differences among them, in terms of their speed and duration of action, and effects on fracture reduction. Expand
Nitrogen‐Containing Bisphosphonates Inhibit the Mevalonate Pathway and Prevent Post‐Translational Prenylation of GTP‐Binding Proteins, Including Ras
Nitrogen‐containing bisphosphonate drugs cause apoptosis following inhibition of post‐translational prenylation of proteins such as Ras, and the data support the view that clodronate acts by a different mechanism. Expand
Cellular and molecular mechanisms of action of bisphosphonates
Bisphosphonates currently are the most important class of antiresorptive agents used in the treatment of metabolic bone diseases, including tumor‐associated osteolysis and hypercalcemia, Paget'sExpand
Molecular Mechanisms of Action of Bisphosphonates: Current Status
Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect osteoclasts in vivo but could also have direct effects on other cell types, such as tumor cells. Expand
Bone remodelling at a glance
The bone remodelling cycle maintains the integrity of the skeleton through the balanced activities of its constituent cell types, including the bone-forming osteoblast, a cell that produces the organic bone matrix and aids its mineralisation during remodelling. Expand
New insights into the molecular mechanisms of action of bisphosphonates.
  • M. Rogers
  • Chemistry, Medicine
  • Current pharmaceutical design
  • 30 November 2003
Identification of FPP synthase as the target of nitrogen-containing bisphosphonates has also helped explain the molecular basis for the adverse effects of these agents in the GI tract and on the immune system. Expand
Biochemical and molecular mechanisms of action of bisphosphonates.
These discoveries are also giving insights into some of the adverse effects of bisphosphonates, such as the acute phase reaction that is triggered by inhibition of FPP synthase in peripheral blood monocytes. Expand
The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo
GPR55 is a G protein-coupled receptor recently shown to be activated by certain cannabinoids and by lysophosphatidylinositol (LPI). However, the physiological role of GPR55 remains unknown. Given theExpand
Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates.
The potency of a wider range of nitrogen-containing bisphosphonates, including the highly potent, heterocycle-containing zoledronic acid and minodronate, is examined, finding a clear correlation between the ability to inhibit farnesyl diphosphate synthase in vitro, and to inhibit protein prenylation in cell-free extracts and in purified osteoclasts in vitro and in vivo. Expand
Bisphosphonates: from the laboratory to the clinic and back again.
The marked structure-activity relationships observed among more complex compounds indicate that the pharmacophore required for maximal activity not only depends upon the bisphosphonate moiety but also on key features, e.g., nitrogen substitution in alkyl or heterocyclic side chains. Expand