We assessed if antiresorptive treatment can prevent aromatase inhibitor-induced bone loss in patients with early breast cancer. We observed that patients who did not receive antiresorptive treatment had a 20.8-fold increase in risk of bone loss after 24 months of aromatase inhibitors therapy. PURPOSE: This study aimed to describe changes in femoral and lumbar bone mineral density (BMD) after 24 months of aromatase inhibitors (AIs) and antiresorptive treatment in postmenopausal women with estrogen receptor-positive breast cancer. METHODS: Prospective, longitudinal study in a real-life setting with a 2-year follow-up. Patients underwent a complete baseline bone assessment including clinical assessment, biological evaluation, BMD measurement, and spine X-ray. Antiresorptive treatment was prescribed to patients with a T-score < - 2 or a T-score < - 1.5 SD with additional osteoporosis risk factors. A follow-up bone assessment was carried out after 24 months. RESULTS: Among 328 patients referred to our center, 168 patients (67.7 ± 10.6 years) were included in our study, and 144 were eligible for antiresorptive treatment. After 24 months, patients receiving antiresorptive treatment experienced a significant increase of + 6.28% in femoral-BMD (F-BMD) and + 7.79% in lumbar-BMD (L-BMD). This increase was not significantly different between osteoporotic and osteopenic patients. Conversely, patients not receiving antiresorptive treatment presented significant F-BMD and L-BMD loss regardless of the baseline BMD. In the multivariate logistic model, the lack of antiresorptive treatment was the only predictive factor for major femoral bone loss with a 20.83 odds ratio (CI95%:4.2-100, p < 0.001). CONCLUSION: This real-life study confirmed that antiresorptive treatment significantly increases femoral and lumbar BMD regardless of the baseline BMD in postmenopausal patients receiving AIs for early breast cancer. Patients who did not receive antiresorptive treatment had a 20.8-fold increased risk of major bone loss. Nevertheless, the best threshold to adopt for starting antiresorptive agents remains undetermined.