Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors

Background: Aromatase inhibitors (Als) are a novel hormonal. therapy for patients with breast cancer. However, Als can cause bone loss by blocking estrogen production. This study aims to assess the association between Als and treatment-related bone loss in a large managed-care population of women with breast cancer. Patients and Methods: With use of medical and pharmacy claims, data from > 5 million beneficiaries between January 1, 1998, and January 31, 2005, we identified 12,368 patients with a 2 breast cancer claims in a 6-month period who also had no bone metastases and no previous osteoporosis or fracture claims. Patients who had received antiestrogen (eg, tomoxifen) therapy were also excluded. One thousand three hundred fifty-four patients receiving an Al (anastrozole, exemestane, or letrozole) were compared with 11,014 controls who did not receive an Al with respect to their risk of bone loss. The observation stari date for the Al and control groups was defined as the service date of the first Al claim and breast cancer claim, respectively. The endpoints include (1) bone loss, consisting of osteoporosis or osteopenia, and (2) clinical fractures. Results: The univariate analysis found that the prevalence of bone loss was 8.7% in the Al group versus 7.1% in the control group, resulting in a significant relative risk of 1.3 (95% confidence interval [CI], 1.1-1.6; P = 0.01). The prevalence of bone fracture was also significantly increased in the Al group compared with the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI, 1.2-1.6, P = 0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained significantly higher in the Al group than in the non-Al group, with a 27% (95% CI, 4%-55%; P = 0.02) and 21% (95% CI, 3%-43%; P = 0.02) increase in the risk of bone loss and fractures, respectively. Conclusion: This retrospective longitudinal analysis of a large cohort of patients with breast cancer corroborates previous findings from smaller clinical trials and demonstrates that Al therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to reduce bone loss risk are warranted in women receiving an Al for breast cancer.