Vertebral Fractures Beyond Bone Density in Breast Cancer: A Real-World Study of Endocrine Therapy and FRAX Reclassification

Background: Endocrine therapy for hormone receptor-positive breast cancer is associated with accelerated bone loss and increased fracture risk. Vertebral fractures (VFs) are frequently asymptomatic and remain underdiagnosed, potentially leading to underestimation of fracture risk. Methods: We conducted a cross-sectional real-world study that included 172 women with breast cancer (mean age 58.2 ± 12.0 years), the majority receiving aromatase inhibitors. Vertebral fractures were assessed using vertebral fracture assessment (VFA) during dual-energy X-ray absorptiometry (DXA). Bone mineral density (BMD), trabecular bone score (TBS), quantitative ultrasound (QUS), and FRAX® scores were evaluated. Results: Vertebral fractures were identified in 13% of patients, and 78% of these occurred in women with normal or osteopenic BMD. Age was independently associated with VFs, while conventional densitometric and non-densitometric parameters showed limited discriminatory ability. The incorporation of VFA-detected fractures into FRAX significantly increased estimated fracture risk (hip fracture risk: 0.8% vs. 4.1%, p = 0.008). Conclusions: Vertebral fractures are common and frequently unrecognized in women receiving endocrine therapy and are not adequately captured by BMD. Routine use of VFA during DXA substantially improves fracture risk assessment and leads to a clinically meaningful reclassification of FRAX estimates. These findings support a more comprehensive approach to skeletal risk evaluation in this population.