Automated Opportunistic Bone Mineral Density Assessment at Low-Dose CT Lung Cancer Screening: Incident Vertebral Fractures and Mortality

Background Low-dose CT (LDCT) for lung cancer screening enables opportunistic volumetric bone mineral density (vBMD) assessment, but its prognostic value is unclear. Purpose To evaluate fully automated LDCT-derived vBMD for predicting vertebral fractures and its association with mortality in individuals who heavily smoke. Materials and Methods This secondary analysis included 55-74-year-old individuals who heavily smoked (≥30 pack-years) from the CT arm of the National Lung Screening Trial (NLST), a multicenter randomized controlled trial of LDCT versus radiography (participants recruited August 2002 to April 2004). Automated SpineQ software (Bonescreen) was used to measure thoracic and lumbar vBMD (normal, ≥120 mg/cm3; low bone mass [osteopenia], 80 to <120 mg/cm3; osteoporosis, <80 mg/cm3) and vertebral fractures (Genant scale). The outcomes included 1- and 2-year incident vertebral fractures and 6-year mortality (active follow-up to 2009). Poisson and Cox models were adjusted for demographic variables, available comorbidities, and baseline vertebral fractures. Results The NLST included 26 722 participants in the CT arm, with 21 856 included in the present analysis (mean age, 61 years ± 5 [SD]; 12 854 male participants). The 2-year vertebral fracture incidence (n = 18 211 participants with 2-year LDCT) was 0.9% for those with normal bone mass, 2.0% for those with low bone mass (adjusted relative risk, 2.07 [95% CI: 1.70, 2.53]), and 5.9% for those with osteoporosis (adjusted relative risk, 3.40 [95% CI: 2.69, 4.30]). Mortality risk (n = 21 447 participants with completed follow-up [median, 6.65 years]) was associated with osteoporotic vBMD in men (adjusted hazard ratio, 1.24 [95% CI: 1.02, 1.50]). Conclusion Fully automated opportunistic assessment of spinal vBMD predicted vertebral fracture risk and was associated with mortality in men after adjustment. Individuals with osteoporotic vBMD who heavily smoked had a 2-year fracture incidence above the 5% treatment threshold according to current osteoporosis guidelines. Clinical trial registration no. NCT00047385 © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Bredella in this issue.