Background: The impact of long-term adjuvant therapy with aromatase inhibitors (Als) on vertebral fracture (VF) risk is still unclear. Objective: In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during Al therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels. Results: We consecutively included 263 postmenopausal women with hormone receptor-positive early BC. One hundred-sixty-nine women were Al-naive, and 94 were Al-treated. Al-treated patients had lower BMD at total hip (p = 0.01) and lumbar spine (p = 0.03), higher serum vitamin D (p < 0.001) and parathyroid hormone (p = 0.006) values as compared to Al-naive patients. The prevalence of VFs was 18.9% in Al-naive patients, and 31.2% in those assessed during Al therapy (odds ratio 1.90, 95% CI 1.1-3.5, p = 0.03). In Al-naive patients, VFs were associated with older age (p = 0.002) and lower BMD values at femoral neck (p = 0.04) and total hip (p = 0.007), whereas VFs occurred without association with any parameter analyzed in Al-treated patients. In Al-treated group, the prevalence of VFs was not significantly different between patients with osteoporosis and those with normal BMD (36.7% vs. 20.0%; p = 031). Conclusions: In women with early BC, Al therapy is associated with high prevalence of radiological VFs, which were shown to be independent of BMD values during the adjuvant treatment. These findings may be clinically relevant since they may lead to a change in management of Al-induced skeletal fragility. Specifically, the results of this study provide a rationale for performing a morphometric evaluation of VFs in all women undergoing treatment with Als. (C) 2017 Elsevier Inc. All rights reserved.