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 receptor-positive 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 receptor-positive 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.