a direct antitumor effect and to synergistically augment the effects of other antitumor agents in osteosarcoma cells. Zoledronic acid has shown significant benefits versus placebo over three years, with a reduced number of vertebral fractures and improved markers of bone density. An annual dose of zoledronic acid may also prevent recurring fractures in patients with a previous hip fracture. Zoledronic acid also attenuates accumulation of DNA damage in mesenchymal stem cells and protects their function. With hormone therapy for breast cancer An increase in disease-free survival (DFS) was found in the ABCSG-12 trial, in which 1,803 premenopausal women with endocrine-responsive early breast cancer received anastrozole with zoledronic acid. A retrospective analysis of the AZURE trial data revealed a DFS survival advantage, particularly where estrogen had been reduced. In a meta-analysis of trials where upfront zoledronic acid was given to prevent aromatase inhibitor-associated bone loss, active cancer recurrence appeared to be reduced. "The results of clinical studies of adjuvant treatment on early-stage hormone-receptor-positive breast-cancer patients under hormonal treatment – especially with the bisphosphonate zoledronic acid – caused excitement because they demonstrated an additive effect on decreasing disease relapses at bone or other sites. A number of clinical and in vitro and in vivo preclinical studies, which are either ongoing or have just ended, are investigating the mechanism of action and antitumoral activity of bisphosphonates." A 2010 review concluded that "adding zoledronic acid 4 mg intravenously every 6 months to endocrine therapy in premenopausal women with hormone receptor-positive early breast cancer ... is cost-effective from a US health care system perspective". References External links Bisphosphonates Farnesyl pyrophosphate synthase inhibitors Novartis brands Imidazoles World Health Organization essential medicines Wikipedia medicine articles ready to translate