Among patients with early breast cancer receiving aromatase inhibitors, excess adiposity emerged as a novel risk factor for vertebral fracture progression, whereas higher muscle mass was protective, according to a retrospective cohort study by Schivardi et al published in JAMA Network Open.
“These findings support incorporating body-composition assessment into fracture-risk evaluation and preventive strategies for patients undergoing aromatase inhibitor therapy,” the investigators commented.
Study Details
The investigators focused on 769 White women (median age = 63 years; median body mass index [BMI] = 24.6; 76.8% postmenopausal) with histologically confirmed stage I to III breast cancer without bone metastases who received adjuvant endocrine therapy with aromatase inhibitors alone (83.2%), a luteinizing hormone–releasing hormone agonist plus aromatase inhibitors (14.9%), or a luteinizing hormone–releasing hormone agonist plus tamoxifen (1.9%) at a single center from September 2014 to June 2024. Patients with prior tamoxifen treatment or significant comorbidities affecting skeletal fragility were excluded.
All patients underwent at least two dual-energy X-ray absorptiometry scans, including at baseline and 24 months (± 6 months), to assess body composition and bone fragility. Excess adiposity was defined as a fat mass percentage greater than 40.8%. Vertebral fracture progression was defined as a new vertebral fracture and/or worsening of a preexisting vertebral fracture by at least one Genant grade, a scoring system used to classify spinal compression fractures from zero (no fracture) to three (severe fracture).
The association between excess adiposity and vertebral fracture progression was assessed using a joint model, with extended Cox regression used to evaluate time-dependent associations. Associations with bone mineral density, trabecular bone score, appendicular lean mass index, and traditional fracture risk factors were examined in secondary analyses.
Key Findings
A total of 69 patients (9.0%) experienced vertebral fracture progression during follow-up.
Excess adiposity appeared to be independently associated with a twofold higher risk of vertebral fracture progression (adjusted hazard ratio [HR] = 2.00, 95% confidence interval [CI] = 1.44–2.82; P < .001).
Higher appendicular lean mass index (HR = 0.38, 95% CI = 0.22–0.65; P < .001) and bone mineral density (HR = 0.79, 95% CI = 0.66–0.94; P = .01) were both found to be associated with a reduced risk of vertebral fracture progression.
The investigators concluded, “In this retrospective single-center longitudinal cohort study, adiposity excess was independently associated with a more than twofold increased risk of vertebral fracture progression in postmenopausal women with early breast cancer.”
“These findings highlight fat mass percentage–based assessment as a clinically relevant measure for fracture risk stratification, identifying high-risk patients who would be missed by BMI alone,” they added. “Additionally, higher appendicular lean mass index was inversely associated with fracture risk, supporting the role of muscle preservation through physical activity in this population.”
Deborah Cosentini, MD, of the University of Brescia, Italy, is the corresponding author of the article in JAMA Network Open.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
