Definition
Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. These compounds are stable analogues of the inorganic pyrophosphate (PPi), which is an endogenous regulator of bone mineralization.
Characteristics
Bisphosphonates were developed in the nineteenth century for industrial use, in particular as “water softeners.” The first clinical use of bisphosphonates in humans was in the 1960s for the treatment of Paget disease, a focal disorder of bone remodeling due to abnormally increased osteoclast-mediated bone resorption. So far, bisphosphonates have been successfully studied in several clinical disorders characterized by an alteration in bone resorption, such as metastatic and osteolytic bone diseases, hypercalcemia of malignancy, and osteoporosis.
All bisphosphonates share a common structure which consists of two phosphate groups attached to a single carbon atom (P-C-P) (See Fig. 1).
Generic structure of bisphosphonates
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References
Body JJ (2006) Bisphosphonates for malignancy-related bone disease: current status, future developments. Support Care Cancer 14:408–418
Early Breast Cancer Trialists’ Collaborative Group (2015) Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomized trials. Lancet 386:1353–61
Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822
Garg A, Leitzel K, Ali S, Lipton A (2015) Antiresorptive therapy in the management of cancer treatment-induced bone loss. Curr Osteoporos Rep 13:73–77
Henry DH, Costa L, Goldwasser F et al (2011) Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29:1125–1132
Hortobagyi GN (2005) Moving into the future: treatment of bone metastases and beyond. Cancer Treat Rev 31(Suppl 3):9–18
Ibrahim MF, Mazarello S, Shorr R et al (2015) Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis. Ann Oncol 26:2205–2213
Khan AA, Morrison A, Hanley DA et al (2014) Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 30:3–23
Morgan GJ, Davies FE, Gregory WM et al (2010) First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 376:1989–1999
Russell RG (2006) Bisphosphonates: from bench to bedside. Ann N Y Acad Sci 1068:367–401
Saad F, Gleason DM, Murray R, Zoledronic Acid Prostate Cancer Study Group et al (2004) Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96:879–882
Van Poznak CH, Temin S, Yee GC et al (2011) American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol 29:1221–1227
Wong MH, Stockler MR, Pavlakis N (2012) Bisphosphonates and other bone agents for breast cancer. Cochrane Database Syst Rev 2:CD003474
See Also
(2012) Alkyl. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 132. doi:10.1007/978-3-642-16483-5_181
(2012) Bone resorption. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 446. doi:10.1007/978-3-642-16483-5_684
(2012) Hydroxyapatite. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 1779. doi:10.1007/978-3-642-16483-5_2890
(2012) Hydroxyl group. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 1779. doi:10.1007/978-3-642-16483-5_2893
(2012) Jaw osteonecrosis. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 1926. doi:10.1007/978-3-642-16483-5_3175
(2012) Paget disease. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 2758. doi:10.1007/978-3-642-16483-5_4345
(2012) Renal cancer. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, pp 3225–3226. doi:10.1007/978-3-642-16483-5_6575
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Guarneri, V. (2015). Bisphosphonates. In: Schwab, M. (eds) Encyclopedia of Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27841-9_660-2
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DOI: https://doi.org/10.1007/978-3-642-27841-9_660-2
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