Excess Adiposity Linked to Vertebral Fracture Risk in Early Breast Cancer

Aromatase inhibitors serve as a standard adjuvant treatment for hormone receptor-positive early breast cancer, but the therapy is known to accelerate bone loss and increase fracture risk.

Excess Adiposity Linked to Vertebral Fracture Progression in Early Breast Cancer Therapy

The investigation focused on 769 White women with a median age of 63 years and a median body mass index (BMI) of 24.6. Among the participants, 76.8% were postmenopausal, and all had histologically confirmed stage I to III breast cancer without bone metastases. Patients were treated at a single center between September 2014 and June 2024.

Study Design and Patient Cohort

To evaluate body composition and bone fragility, all patients underwent at least two dual-energy X-ray absorptiometry (DXA) scans, including a baseline scan and a follow-up scan at 24 months (plus or minus 6 months). Participants received adjuvant endocrine therapy consisting of aromatase inhibitors alone in 83.2% of cases, a luteinizing hormone–releasing hormone agonist plus aromatase inhibitors in 14.9% of cases, or a luteinizing hormone–releasing hormone agonist plus tamoxifen in 1.9% of cases. The study required an Eastern Cooperative Oncology Group score of 0 to 1 and an estimated life expectancy exceeding 18 months. Patients with prior tamoxifen treatment or significant comorbidities affecting skeletal fragility were excluded.

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Excess adiposity in the study was defined as a fat mass percentage greater than 40.8%. Vertebral fracture progression was defined as a new vertebral fracture and/or the worsening of a preexisting vertebral fracture by at least one Genant grade, which is a scoring system used to classify spinal compression fractures from zero for no fracture to three for a severe fracture. Over a median follow-up of 45.6 months, a total of 69 patients, representing 9.0% of the cohort, experienced vertebral fracture progression.

Key Findings on Adiposity and Muscle Mass

The research revealed that excess adiposity was independently associated with a twofold higher risk of vertebral fracture progression, with an adjusted hazard ratio of 2.00, a 95% confidence interval of 1.44 to 2.82, and a P value of less than .001. In contrast, higher appendicular lean mass index and higher bone mineral density were both found to be protective, showing associated reduced risks of fracture progression with adjusted hazard ratios of 0.38 and 0.79, respectively. After adjustment, prior fractures were not independently associated with fracture progression.

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Furthermore, standard BMI classifications often failed to capture this risk. A BMI below 30 kg/m² failed to detect excess adiposity in 28.9% of DXA assessments, and among women with a normal BMI below 25 kg/m², excess adiposity remained associated with a substantially higher vertebral fracture risk.

Clinical Implications and Limitations

The investigators concluded that incorporating body-composition assessments using DXA-derived fat mass measurements can improve fracture risk stratification by identifying high-risk patients who would otherwise be missed by BMI alone. They also emphasized that higher appendicular lean mass index was inversely associated with fracture risk, supporting the role of muscle preservation through physical activity in this patient population.

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The authors acknowledged several study limitations, including the retrospective single-center design, the widespread use of bone-targeting agents, and a lack of data on visceral adiposity. Despite these constraints, the findings suggest that clinicians should consider integrating body-composition evaluations into routine fracture-risk evaluation and preventive strategies for patients undergoing aromatase inhibitor therapy.