Predicting hip fracture type with cortical bone mapping (CBM) in the Osteoporotic Fractures in Men (MrOS) study

Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual energy X-ray (DXA)-based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have sub-divided fracture into types, since this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The osteoporotic fractures in men (MrOS) study is a predictive case-cohort study of men over 65: we analyse 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5,994. To our knowledge, this is the largest QCT-based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We demonstrate that both cortical mass surface density, and endocortical trabecular BMD, show significant difference in fracture cases vs. cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA-based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave-one-out cross-validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 (trochanteric fractures) and 0.76 to 0.82 (femoral neck fractures). In contrast, adding DXA-based BMD to a CBM-based predictive model does not result in any significant improvement.The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Ageing (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. GMT, AHG, DMB and KESP contributed to the conception and design of the study. All authors were involved in the analysis or interpretation of the data, contributed to the manuscript, and approved the final version. KESP acknowledges the support of the NIHR Biomedical Research Centre, Cambridge. KESP received funding from Arthritis Research UK (ARUK ref. no. 20109). GMT takes responsibility for the integrity of the data analysis.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.255