Archives
br Conclusion br Conflict of interest statement br
Conclusion
Conflict of interest statement
Authors\' contribution
Introduction
There are two classes of bisphosphonates that differ with regard to structure and mechanism of action [1]. The first one includes pyrophosphate-resembling bisphosphonates, such as clodronate and etidronate, which are metabolically incorporated into nonhydrolyzable adenospine tri-phosphate (ATP) analogues that act as inhibitors of ATP-dependent enzymes. The second class which is more recent and potent includes nitrogen-containing bisphosphonates (N-BPs), such as alendronate, pamidronate, risedronate, ibandronate and zoledronic buy A 779 (ZA).
N-BPs inhibit a key enzyme, farnesyl diphosphonate (FPP) synthase, in the biosynthetic mevalonate pathway. As a result, these compounds interfere with a variety of cellular functions essential for the bone-resorbing activity and survival of osteoclasts. Several intermediates in this pathway (Fig. 1), including farnesyl pyrophosphate and geranylgeranyl pyrophosphate, are required for the post-translational modification (i.e., prenylation) of guanosine triphosphate-binding proteins such as Ras, Rho, and Rac. These signalling molecules are involved in the regulation of cell proliferation, cell survival, and cytoskeletal organization [2,3].
ZA is reported to be more potent inhibitor of farnesyl diphosphate synthase than the other bisphosphonates risedronate, ibandronate, incadronate, alendronate, and pamidronate [4].
Conclusion
Conflict of interest statement