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.

ICGM-FRAX: Iterative Cross Graph Matching for Hip Fracture Risk Assessment using Dual-energy X-ray Absorptiometry Images

Hip fractures represent a major health concern, particularly among the elderly, often leading decreased mobility and increased mortality. Early and accurate detection of at risk individuals is crucial for effective intervention. In this study, we propose Iterative Cross Graph Matching for Hip Fracture Risk Assessment (ICGM-FRAX), a novel approach for predicting hip fractures using Dual-energy X-ray Absorptiometry (DXA) images. ICGM-FRAX involves iteratively comparing a test (subject) graph with multiple template graphs representing the characteristics of hip fracture subjects to assess the similarity and accurately to predict hip fracture risk. These graphs are obtained as follows. The DXA images are separated into multiple regions of interest (RoIs), such as the femoral head, shaft, and lesser trochanter. Radiomic features are then calculated for each RoI, with the central coordinates used as nodes in a graph. The connectivity between nodes is established according to the Euclidean distance between these coordinates. This process transforms each DXA image into a graph, where each node represents a RoI, and edges derived by the centroids of RoIs capture the spatial relationships between them. If the test graph closely matches a set of template graphs representing subjects with incident hip fractures, it is classified as indicating high hip fracture risk. We evaluated our method using 547 subjects from the UK Biobank dataset, and experimental results show that ICGM-FRAX achieved a sensitivity of 0.9869, demonstrating high accuracy in predicting hip fractures.

A Staged Approach using Machine Learning and Uncertainty Quantification to Predict the Risk of Hip Fracture

Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors. We propose a novel staged model that combines advanced imaging and clinical data to improve predictive performance. By using CNNs to extract features from hip DXA images, along with clinical variables, shape measurements, and texture features, our method provides a comprehensive framework for assessing fracture risk. A staged machine learning-based model was developed using two ensemble models: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and DXA imaging features). This staged approach used uncertainty quantification from Ensemble 1 to decide if DXA features are necessary for further prediction. Ensemble 2 exhibited the highest performance, achieving an AUC of 0.9541, an accuracy of 0.9195, a sensitivity of 0.8078, and a specificity of 0.9427. The staged model also performed well, with an AUC of 0.8486, an accuracy of 0.8611, a sensitivity of 0.5578, and a specificity of 0.9249, outperforming Ensemble 1, which had an AUC of 0.5549, an accuracy of 0.7239, a sensitivity of 0.1956, and a specificity of 0.8343. Furthermore, the staged model suggested that 54.49% of patients did not require DXA scanning. It effectively balanced accuracy and specificity, offering a robust solution when DXA data acquisition is not always feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of the advanced modeling strategies. Our staged approach could identify individuals at risk with a high accuracy but reduce the unnecessary DXA scanning. It has great promise to guide interventions to prevent hip fractures with reduced cost and radiation.