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Abstract
Zoledronic acid, a nitrogen-containing bisphosphonate, is firmly established in the management of metastatic bone disease. It inhibits farnesyl diphosphonate synthase within the mevalonate pathway and, through this mechanism, is a potent inhibitor of osteoclast-mediated bone resorption. In addition, there are preclinical data suggesting that farnesyl diphosphonate synthase inhibition by zoledronic acid has anti-tumor effects in breast cancer. Adjuvant therapies for early breast cancer are associated with substantial decreases in bone mineral density. Results from three clinical trials, ABCSG-12, Z-FAST and ZO-FAST, indicate that the addition of twice-yearly zoledronic acid to standard adjuvant endocrine therapy in premenopausal and postmenopausal patients with hormone receptor-positive breast cancer prevents cancer treatment-induced bone loss. Moreover, it is becoming evident that it may also exert anticancer effects in an estrogen-deprived state in the adjuvant and neoadjuvant setting. However, long-term side effects need to be taken into consideration for treatment decisions.
Financial & competing interests disclosure
Richard Greil reports serving as a consultant for and receiving honoraria for participation on advisory boards from Novartis and AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.