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Pathway Description
Tiludronic Acid Action Pathway
Homo sapiens
Drug Action Pathway
Tiludronic acid is a first-generation bisphosphonate used to treat Paget's disease, similar to etidronic acid and clodronic acid. Tiludronic acid binds to hydroxylapatite in the bone, during bone resorption it is released and taken up by osteoclasts through endocytosis. Once inside the osteoclast, it is released into the cytosol and goes to interrupt osteoclast activity and function. Tiludronic acid has a structure similar to pyrophosphate and due to this can be incorporated into ATP analogues that cannot be hydrolyzed. Due to this the osteoclast cannot utilize ATP and begins to go through apoptosis. If a patient has an overdose they may present with hypocalcemia, which can be treated with supportive care. Tiludronic acid should be taken 2 hours before or after consuming a meal and/or calcium supplements. Avoiding taking it with antacids as it will greatly reduce the bioavailability.
References
Tiludronic Acid Pathway References
Qin A, Cheng TS, Pavlos NJ, Lin Z, Dai KR, Zheng MH: V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption. Int J Biochem Cell Biol. 2012 Sep;44(9):1422-35. doi: 10.1016/j.biocel.2012.05.014. Epub 2012 May 29.
Pubmed: 22652318
Russell RG, Watts NB, Ebetino FH, Rogers MJ: Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun;19(6):733-59. doi: 10.1007/s00198-007-0540-8.
Pubmed: 18214569
Sansom LN, Necciari J, Thiercelin JF: Human pharmacokinetics of tiludronate. Bone. 1995 Nov;17(5 Suppl):479S-483S. doi: 10.1016/8756-3282(95)00259-6.
Pubmed: 8573422
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