DXA-Derived Skeletal Phenotypes and Hip Fracture Risk: A Backdoor-Adjusted Causal Analysis

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.

PF-DAformer: Proximal Femur Segmentation via Domain Adaptive Transformer for Dual-Center QCT

Quantitative computed tomography (QCT) plays a crucial role in assessing bone strength and fracture risk by enabling volumetric analysis of bone density distribution in the proximal femur. However, deploying automated segmentation models in practice remains difficult because deep networks trained on one dataset often fail when applied to another. This failure stems from domain shift, where scanners, reconstruction settings, and patient demographics vary across institutions, leading to unstable predictions and unreliable quantitative metrics. Overcoming this barrier is essential for multi-center osteoporosis research and for ensuring that radiomics and structural finite element analysis results remain reproducible across sites. In this work, we developed a domain-adaptive transformer segmentation framework tailored for multi-institutional QCT. Our model is trained and validated on one of the largest hip fracture related research cohorts to date, comprising 1,024 QCT images scans from Tulane University and 384 scans from Rochester, Minnesota for proximal femur segmentation. To address domain shift, we integrate two complementary strategies within a 3D TransUNet backbone: adversarial alignment via Gradient Reversal Layer (GRL), which discourages the network from encoding site-specific cues, and statistical alignment via Maximum Mean Discrepancy (MMD), which explicitly reduces distributional mismatches between institutions. This dual mechanism balances invariance and fine-grained alignment, enabling scanner-agnostic feature learning while preserving anatomical detail.