Opportunistic hip fracture risk prediction in Men from X-ray: Findings from the Osteoporosis in Men (MrOS) Study

Osteoporosis is a common disease that increases fracture risk. Hip fractures, especially in elderly people, lead to increased morbidity, decreased quality of life and increased mortality. Being a silent disease before fracture, osteoporosis often remains undiagnosed and untreated. Areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) is the gold-standard method for osteoporosis diagnosis and hence also for future fracture prediction (prognostic). However, the required special equipment is not broadly available everywhere, in particular not to patients in developing countries. We propose a deep learning classification model (FORM) that can directly predict hip fracture risk from either plain radiographs (X-ray) or 2D projection images of computed tomography (CT) data. Our method is fully automated and therefore well suited for opportunistic screening settings, identifying high risk patients in a broader population without additional screening. FORM was trained and evaluated on X-rays and CT projections from the Osteoporosis in Men (MrOS) study. 3108 X-rays (89 incident hip fractures) or 2150 CTs (80 incident hip fractures) with a 80/20 split were used. We show that FORM can correctly predict the 10-year hip fracture risk with a validation AUC of 81.44 +- 3.11% / 81.04 +- 5.54% (mean +- STD) including additional information like age, BMI, fall history and health background across a 5-fold cross validation on the X-ray and CT cohort, respectively. Our approach significantly (p < 0.01) outperforms previous methods like Cox Proportional-Hazards Model and \frax with 70.19 +- 6.58 and 74.72 +- 7.21 respectively on the X-ray cohort. Our model outperform on both cohorts hip aBMD based predictions. We are confident that FORM can contribute on improving osteoporosis diagnosis at an early stage.

An Analysis by Synthesis Method that Allows Accurate Spatial Modeling of Thickness of Cortical Bone from Clinical QCT

Osteoporosis is a skeletal disorder that leads to increased fracture risk due to decreased strength of cortical and trabecular bone. Even with state-of-the-art non-invasive assessment methods there is still a high underdiagnosis rate. Quantitative computed tomography (QCT) permits the selective analysis of cortical bone, however the low spatial resolution of clinical QCT leads to an overestimation of the thickness of cortical bone (Ct.Th) and bone strength. We propose a novel, model based, fully automatic image analysis method that allows accurate spatial modeling of the thickness distribution of cortical bone from clinical QCT. In an analysis-by-synthesis (AbS) fashion a stochastic scan is synthesized from a probabilistic bone model, the optimal model parameters are estimated using a maximum a-posteriori approach. By exploiting the different characteristics of in-plane and out-of-plane point spread functions of CT scanners the proposed method is able assess the spatial distribution of cortical thickness. The method was evaluated on eleven cadaveric human vertebrae, scanned by clinical QCT and analyzed using standard methods and AbS, both compared to high resolution peripheral QCT (HR-pQCT) as gold standard. While standard QCT based measurements overestimated Ct.Th. by 560% and did not show significant correlation with the gold standard ($r^2 = 0.20,\, p = 0.169$) the proposed method eliminated the overestimation and showed a significant tight correlation with the gold standard ($r^2 = 0.98,\, p < 0.0001$) a root mean square error below 10%.