Bisphosphonates are the cornerstone of

Bisphosphonates are the cornerstone of management in postmenopausal osteoporosis with randomised trial evidence of reductions in vertebral fractures for ibandronate [15] and both vertebral and non-vertebral fracture rates for alendronate [16], risedronate [17], and zoledronic Teneligliptin hydrobromide [18]. Ibandronate is a highly potent nitrogen containing bisphosphonate that can be administered both intravenously and orally. Using the oral route of administration, a single dose every month in post menopausal women with osteoporosis led to similar changes in BMD and bone turnover markers as daily treatment [19]. This simple treatment is potentially highly attractive for cancer patients and offers an alternative to 6 monthly intravenous treatment with zoledronic acid [20–21] or weekly oral therapy with risedronate [22]. Given the concerns about the long-term effects of anastrozole on bone health, the ARIBON study was designed to evaluate the effect of bisphosphonate treatment on patients considered at risk for the development of osteoporosis during 5 years of anastrazole therapy. The 2-year results have been published previously [23] and showed that oral ibandronate was able to prevent bone loss and reduce markers of bone turnover in patients with osteopenia and osteoporosis. Here we present the final 5 year study results.
Methods 131 postmenopausal women with a histologically confirmed diagnosis of oestrogen receptor positive breast cancer from two cancer centres (Sheffield and Leeds) were recruited. Details of the study eligibility and methods have been published previously [23]. Briefly, patients were excluded if menopause had been induced by either prior chemotherapy or drug therapy (e.g. goserelin). Other exclusion criteria included concurrent administration of medications with effects on bone, abnormal renal function, disorders of bone metabolism and previous bilateral hip fractures or bilateral hip prostheses that would have hindered reliable BMD assessments. Following informed consent, patients underwent a baseline assessment of BMD at the LS and TH before commencing anastrozole and study entry. All patients received anastrozole 1mg once a day and calcium (500mg) and vitamin D (400IU) supplements daily. Patients with normal BMD (T score >−1 at both the LS and TH) were allocated to an observation group with a follow-up BMD assessment at 2 years. No further protocol-directed follow-up of these patients after year 2 was required, and they were treated according to current clinical guidelines at the two participating institutions. Patients with osteoporosis (T score <−2.5 at either the LS or TH) received open label ibandronate 150mg every 28 day by mouth for the 5 years of the study. Patients classified as osteopenic (T-scores of >−2.5 and <−1.0 at either the LS and TH) were randomly assigned in a double blind manner on a 1:1 basis to receive either ibandronate tablets 150mg every 28 day or placebo tablets of identical appearance also every 28 day for two years. Ibandronate/placebo capsules were taken in an upright position first thing in the morning on an empty stomach and washed down with 100mls water to minimise the risk of oesophageal irritation; no food or drink (other than water) was consumed for at least 30min after taking the study medication. Patients (n=5) who developed osteoporosis whilst taking ibandronate/placebo medication were un-blinded and offered open label ibandronate treatment. After 2 years the randomised treatment was stopped and the treating clinician, depending upon the results of the BMD result at 2 years, offered treatment with open label ibandronate. Local ethics committee approval was obtained at both centres prior to commencing recruitment. The study was sponsored by the University of Sheffield, and funded through unrestricted academic grants from both Roche and Astra Zeneca who also provided ibandronate/placebo and anastrazole study medications respectively. All data were held within the Cancer Clinical Trials Centre at the University of Sheffield. All analyses were performed by the investigators. Neither pharmaceutical company had any input into the analysis or reporting of results. The ARIBON study is registered on the UK department of health national research register. Publication ID N0276137347 (http://www.nrr.nhs.uk).