Opportunistic Osteoporosis Screening Using CT-Derived Volumetric Bone Mineral Density Reference Curves

Computed tomography (CT) scans are a widely available yet underused resource that can be leveraged for opportunistic osteoporosis screening. This study aimed to develop sex- and site-specific reference curves for volumetric bone mineral density (vBMD) to define dual X-ray absorptiometry (DXA)-anchored percentile thresholds for osteoporosis classification, and to evaluate whether these thresholds identified individuals who subsequently sustain a major osteoporotic fracture (MOF). A retrospective cohort of 4,418 clinical CT scans was analyzed, including a subset of 1,088 scans with corresponding DXA imaging within one year. MOF incidence and timing following CT were obtained from linked administrative health data. CT images were segmented with deep learning models to extract the first lumbar vertebra (L1) and femoral neck from which vBMDs were assessed using internal calibration. Sex-specific vBMD centile curves were generated for each region using Generalized Additive Models for Location, Scale and Shape. A receiver operating characteristic analysis with the Youden index defined percentile thresholds that aligned with DXA-defined osteoporosis. Clinical relevance was assessed by determining the proportion of participants classified as osteoporotic by the CT-derived percentile thresholds who subsequently sustained a MOF, and by evaluating the association between CT-defined osteoporosis and time to incident fracture using Cox proportional hazards models. The cohort included 2,368 males and 2,050 females. At the vertebral body, 66.3% (n=67) of female and 41.9% (n=26) of male fracture cases had vBMD values below the CT-defined osteoporosis threshold, consistent with osteoporosis. Among these, 44.8% (n=30) of females and 76.9% (n=20) of males had not undergone DXA screening. Individuals classified as osteoporotic based on CT-derived thresholds had up to 2.86 times higher risk of sustaining an MOF across all vertebral sites in both sexes. These findings indicate that CT-derived vBMD percentile thresholds offer clinically meaningful cut-points for opportunistic screening and support their use as a diagnostic flag for further evaluation.