• Richard Eastell, Judith E Adams, Robert E Coleman, Anthony Howell, Rosemary A Hannon, Jack Cuzick, John R Mackey, Matthias W Beckmann, and Glen Clack.
• Academic Unit of Bone Metabolism, University of Sheffield, UK. r.eastell@sheffield.ac.uk
• J. Clin. Oncol. 2008 Mar 1; 26 (7): 1051-7.

PurposeThe Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (median follow-up, 68 months) has shown that adjuvant anastrozole has superior efficacy and better tolerability than tamoxifen. However, anastrozole reduces circulating estrogen, and low estradiol levels are associated with decreased bone mineral density (BMD) and increased fracture risk. It is therefore important to understand the effects of long-term aromatase inhibitor therapy on BMD.Patients And MethodsThis prospective substudy of the ATAC trial assessed BMD changes in postmenopausal women with invasive primary breast cancer receiving anastrozole (1 mg/d) or tamoxifen (20 mg/d) as adjuvant therapy for 5 years. Lumbar spine and total hip BMD were assessed at baseline and after 1, 2, and 5 years.ResultsOne hundred ninety-seven women from the monotherapy arms of the ATAC trial were recruited onto the bone substudy, and 108 were included in the primary analysis. Among anastrozole-treated patients, there was a decrease in median BMD from baseline to 5 years in lumbar spine (-6.08%) and total hip (-7.24%) compared with the tamoxifen group (lumbar spine, +2.77%; total hip, +0.74%). No patients with normal BMD at baseline became osteoporotic at 5 years.ConclusionAnastrozole is associated with accelerated bone loss over the 5-year treatment period. However, although patients with pre-existing osteopenia are likely to require monitoring and bone-protection strategies, patients with normal BMD would not appear to require monitoring beyond the recommendation for healthy postmenopausal women. The effect of anastrozole on bone should be weighed against its superior efficacy and better tolerability profile versus tamoxifen in the main ATAC trial.

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