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  • br Conclusion br Conflict of interest statement br

    2019-05-15


    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 buy A 779 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