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Pathway Description
Zoledronate Action Pathway
Homo sapiens
Drug Action Pathway
Zoledronate also known as zoledronic acid is a third-generation bisphosphonate used to treat malignancy with hypercalcemia, myeloma and bone metastasis from tumors. Zoledronate is taken up into the bone and binds to hydroxyapatite, during bone resorption zoledronate is released and taken up into the osteoclast by endocytosis. Within the cytosol of the osteoclast, it inhibits geranylgeranyl pyrophosphate synthase and farnesyl pyrophosphate synthase. Without these enzymes components needed for the prenylation of proteins are stopped, and this leads to apoptosis of the osteoclast.
References
Zoledronate Pathway References
Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S: Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007 Nov 1;357(18):1799-809. doi: 10.1056/NEJMoa074941. Epub 2007 Sep 17.
Pubmed: 17878149
Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ: Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002 Feb 28;346(9):653-61. doi: 10.1056/NEJMoa011807.
Pubmed: 11870242
Durie BG, Katz M, Crowley J: Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005 Jul 7;353(1):99-102; discussion 99-102. doi: 10.1056/NEJM200507073530120.
Pubmed: 16000365
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