Systematic Review of Bone Health in Older Women Treated with Aromatase Inhibitors for Early-Stage Breast Cancer

Objectives To review data from randomized controlled trials (RCTs) that evaluate adverse bone outcomes in older women using aromatase inhibitors (AIs) for early-stage hormone receptorpositive breast cancer. Design Systematic review. Setting International RCTs referenced in Medline and EMBASE databases through August 1, 2011. Participants Postmenopausal women with early-stage hormone receptorpositive breast cancer receiving adjuvant endocrine therapy. Measurements Fracture rates and changes in bone turnover markers and bone mineral density. Results Eleven RCTs were identified. The majority of trials included women with a mean age in the 60s; and women aged 75 and older and 80 and older were excluded from two studies. Fracture rates ranged from 0.9% to 11%, with AIs having a 1.5 times higher risk than tamoxifen or placebo. Fracture data were not systematically collected in many of these trials. In a small subpopulation of women, AIs were associated with higher markers of bone turnover and lower bone density. The relationship between age and fracture was not described. Conclusion AIs are associated with low bone density and high fracture risk in women with a mean age in their early 60s. There is a paucity of data describing the effect of baseline fracture risk factors, particularly age, and the longer-term effects on bone health in older women. Future research is needed regarding baseline fracture risk, interventions, and long-term effects on bone in this vulnerable population to inform management decisions to optimize AI duration and ensure quality of life after breast cancer.