The evaluation of the effect of aromatase inhibitor use on bone and bone fragility in early stage hormone receptor positive breast cancer patients

Introduction and Aim: Breast cancer is the most common cancer in women worldwide and a leading cause of cancer related deaths. Hormone receptor-positive breast cancer, particularly, stands out as the most prevalent subtype, constituting 70% of all breast cancer cases. Hormone therapy, applied in both the adjuvant and metastatic stages of this type of breast cancer, necessitates consideration of the menopausal status of patients. The primary objective of this study is to assess the effects of aromatase inhibitor therapy on bone health in hormone receptor-positive breast cancer patients undergoing adjuvant treatment. Specifically, the impact of the treatment on bone will be examined through measurements of patients' bone mineral density, and in this context, potential risks and benefits for bone health will be evaluated. The integration of FRAX (Fracture Risk Assessment Tool) scoring in the clinical practice for assessing fracture risk in this patient population is intended to provide information for informed clinical decision-making processes. Materials and Method: Within the scope of this research, data from 237 patients diagnosed with hormone receptor-positive breast cancer who applied to the Medical Oncology clinics of Başkent University Ankara Hospital and received adjuvant aromatase inhibitor treatment between December 2009 and December 2023 were retrospectively examined. Bone mineral density measurements were conducted during the diagnosis and follow-up processes of these patients. Aromatase inhibitor usage was identified as a risk factor in calculating the FRAX score, which was employed to assess the patients' fracture risk. Throughout the treatment process, the occurrence of fractures and changes in bone mineral density were monitored. Findings and Discussion: The adverse effects of aromatase inhibitors on bone health have been demonstrated in previous studies in the literature. In this study, following the use of aromatase inhibitors, a significant decrease in bone mineral density was observed in the lumbar vertebra, femoral neck, and total femur regions (p<0.0001). The percentage changes in bone mineral density during the follow-up period were determined to be-2.89% for L1-L4,-4.48% for the femoral neck, and-3.17% for the total femur. These findings emphasize the need for monitoring bone health in patients undergoing aromatase inhibitor treatment. In clinical practice, the FRAX score, calculated considering aromatase inhibitor risk factors, stands out as an important indicator in this regard. At the end of our study's average follow-up period of 53.4 months, it was observed that 7.1% of patients (17 patients) developed fragility fractures. The FRAX scores of patients who experienced fractures were significantly higher than the average FRAX score of patients who did not experience fractures (10-year probability of major osteoporotic fracture: 13.9% vs. 9.1%; p=0.001, and for hip fracture: 6.0% vs. 2.6%; p=0.002). Osteoporosis treatment was initiated in 81 patients diagnosed with osteoporosis or at high risk of fractures to prevent fracture development. Osteoporosis treatment commenced after the diagnosis of osteoporosis. The FRAX scores of patients using osteoporosis medication were significantly higher compared to those not using medication (11.9% vs. 8.2% for major osteoporotic fracture; p<0.001, and 4.6% vs. 2.0% for hip fracture; p<0.001). These results suggest that the calculation of the FRAX score as a risk factor in patients using aromatase inhibitors should be taken into consideration and that high FRAX scores may guide clinicians in detecting fracture development in the osteopenia stage and initiating bisphosphonate treatment. Key words: Breast Cancer, Aromatase Inhibitors, FRAX, Osteoporosis, Fragility Fracture