Fracture Risk Prediction in Adults Over 50 Years Old Using DXA and EHR: Comparison of Traditional and Machine Learning Models in Two Large Cohorts
Authors: Jiahe Qian, Hao Dai, Kunyu Yu, Hexin Dong, Xing He, Erik A. Imel, Jiang Bian, Yifan Peng, +1 more
Organizations: Department of Population Health Sciences, Weill Cornell Medicine, New York, USA · Department of Biostatistics & Health Data Science, Indiana University School of Medicine, Indiana, USA · Department of Medicine, School of Medicine, Indiana University, Indiana, USA · Center for Biomedical Informatics, Regenstrief Institute, Indiana, USA · Department of Medicine, Weill Cornell Medicine, New York, USA
Abstract
Accurate fracture risk prediction is important for osteoporosis management, but commonly used clinical tools may not fully use information available in electronic health records (EHRs) and dual-energy X-ray absorptiometry (DXA) reports. We developed and externally validated time-to-event fracture prediction models among adults aged 50 years or older with clinically obtained DXA reports in 2 US health care systems. The development cohort was derived from NewYork-Presbyterian/Weill Cornell Medical Center and the external validation cohort from the Indiana Network for Patient Care. Predictors included demographics, lifestyle factors, prior fracture, comorbidities, medication exposures, osteoporosis treatment history, and DXA-derived T-scores extracted from radiology reports. The outcome was time from index DXA to first incident fragility fracture identified from structured diagnosis codes. We evaluated penalized Cox regression, random survival forest, gradient-boosting survival, and XGBoost survival models using 2 prespecified predictor settings and compared discrimination with clinically reported FRAX major osteoporotic fracture probabilities. The development cohort included 11,510 adults, of whom 858 sustained incident fragility fractures; the external validation cohort included 1,932 adults, of whom 180 sustained fractures. In internal validation, the expanded Cox model achieved a mean Harrell C-index of 0.779, compared with 0.653 for FRAX. In external validation, the corresponding Cox model achieved a Harrell C-index of 0.714, compared with 0.590 for FRAX; gradient-boosting survival had the highest external discrimination (0.725). EHR- and DXA-enhanced models showed better discrimination than clinically reported FRAX scores in this DXA-tested population, but calibration assessment, prospective evaluation, and implementation workflow assessment are needed before clinical use.
Purpose: To compare dual-energy X-ray absorptiometry (DXA)-derived hip skeletal phenotypes in relation to hip fracture risk using prespecified confounder adjustment and to assess whether phenotypes ranked by their backdoor-adjusted average treatment effects (ATEs) improve risk stratification. Methods: We analyzed 21,098 UK Biobank participants with linked health records, hip DXA-derived skeletal measures, and prespecified covariates. Sixteen phenotypes spanning bone mineral content (BMC), bone mineral density (BMD), and T-score across hip-related regions were evaluated. Confounder selection was guided by a prespecified directed acyclic graph (DAG). Backdoor-adjusted ATEs were estimated on the absolute risk-difference scale per standard deviation (SD) increase. Effect heterogeneity was evaluated for total femur BMD, and downstream prediction was assessed using clinical variables combined with phenotypes ranked by ATE magnitude. Results: Among 21,098 participants, 115 had hip fractures. All 16 phenotypes showed negative backdoor-adjusted ATEs per SD increase. The largest ATEs were observed for total femur BMC and total femur BMD, each with a risk difference of -0.0047, corresponding to approximately 4.7 fewer hip fractures per 1,000 participants per SD higher phenotype value. Conditional effects of total femur BMD were stronger among older participants and those with lower BMI. In prediction, clinical variables plus the top 11 ATE-ranked phenotypes achieved higher AUC than FRAX with femoral neck BMD (0.842 vs. 0.709), with higher sensitivity (0.748 vs. 0.443) and similar specificity (0.793 vs. 0.777). Conclusion: DXA-derived hip skeletal phenotypes differed in their backdoor-adjusted ATEs. Phenotype-level causal evaluation may help identify informative DXA measures for risk stratification.
Whole-body dual-energy X-ray absorptiometry (DXA) scans are routinely acquired to measure bone density and regional body composition, leaving their spatial structure largely unused. Here, we show that self-supervised learning (SSL) can convert raw DXA images into representations of systemic health. We introduce LeDXA, a vision model based on a joint-embedding predictive architecture (JEPA) that learns by predicting latent representations rather than reconstructing pixels. Trained from scratch on 11,540 unlabeled Human Phenotype Project scans, LeDXA was evaluated internally and on 47,400 external UK Biobank (UKBB) scans. It improved cross-cohort prediction of prevalent diseases and biomarkers beyond scanner-derived DXA measurements and DINOv3, a state-of-the-art general-purpose model, despite approximately 150,000-fold fewer training images and nearly 40-fold fewer parameters. Over a median 4.3-year UKBB follow-up, LeDXA improved incident disease prediction over tabular DXA measures, with the largest gains for hip and knee arthrosis and type 2 diabetes. For hip arthrosis, 66% of incident cases occurred in the highest-risk quartile versus 41% for tabular measures. Its representations predicted chronological age externally (r = 0.88; mean absolute error = 2.90 years), and the biological-age gap tracked broader disease burden and a 45% higher mortality hazard in the oldest-appearing quartile. The gap also decreased in women after starting hormone-replacement therapy, suggesting it may be modifiable. Genome-wide associations recovered mostly known body-composition and bone-density loci, and LeDXA embeddings were more heritable than DINOv3's. These findings reveal prognostic information in DXA images that conventional readouts discard, learnable with relatively little data and modest compute.
Perioperative risk prediction models are often limited by narrow surgical populations, incomplete intraoperative data, poor calibration, and limited interpretability. We present a domain-structured ensemble framework for perioperative outcome prediction using routinely collected electronic health record (EHR) data. Predictors are organized into patient-related, surgery-related, and anesthetics-related domains. Domain-specific gradient boosting models generate independent risk estimates that are integrated through a logistic regression meta-learner. We demonstrate the framework using postoperative delirium (POD) in a case-control sample of 5,386 surgical encounters (2,693 cases, 2,693 controls) from a statewide health information exchange. POD required both delirium-related ICD codes and a positive Confusion Assessment Method screening within seven postoperative days; patients with preexisting dementia were excluded. The stacked meta-learner achieved AUROC 0.899 (95% CI: 0.891-0.906), precision-recall AUC 0.881, and Brier score 0.126, compared with AUROC 0.849 for the best single-stage model. Domain ablation showed improved discrimination and calibration over a surgery-only model (AUROC 0.879, Brier 0.140). Temporal validation on held-out post-2017 data yielded AUROC 0.915. Calibration was excellent, with intercept -0.006 (95% CI: -0.083 to 0.070) and slope 1.035 (95% CI: 0.982 to 1.088). Decision curve analysis, corrected for case-control sampling, showed positive net benefit across clinically plausible thresholds. The modular framework supports alternative outcomes, extension of predictor domains, and dynamic risk updating, providing a scalable foundation for interpretable, calibration-aware perioperative clinical decision support.