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Osteoporosis is an age-associated disease characterised by low bone mineral density (BMD) and micro-architectural deterioration leading to enhanced fracture risk. Conventional dual-energy X-ray absorptiometry (DXA) analysis has facilitated our understanding of BMD reduction in specific regions of interest (ROIs) within the femur, but cannot resolve spatial BMD patterns nor reflect age-related changes in bone microarchitecture due to its inherent averaging of pixel BMD values into large ROIs. To address these limitations and develop a comprehensive model of involutional bone loss, this paper presents a fully automatic pipeline to build a spatio-temporal atlas of ageing bone in the proximal femur. A new technique, termed DXA region free analysis (DXA RFA), is proposed to eliminate morphological variation between DXA scans by warping each image into a reference template. To construct the atlas, we use unprocessed DXA data from Caucasian women aged 20-97 years participating in three cohort studies in Western Europe ( ,000). A novel calibration procedure, termed quantile matching regression, is proposed to integrate data from different DXA manufacturers. Pixel-wise BMD evolution with ageing was modelled using smooth quantile curves. This technique enables characterisation of spatially-complex BMD change patterns with ageing, visualised using heat-maps. Furthermore, quantile curves plotted at different pixel coordinates showed consistently different rates of bone loss at different regions within the femoral neck. Given the close relationship between spatio-temporal bone loss and osteoporotic fracture, improved understanding of the bone ageing process could lead to enhanced prognostic, preventive and therapeutic strategies for the disease.

Diffusion MRI (dMRI) is a growing imaging technique with the potential to provide biomarkers of tissue variation, such as cellular density, tissue anisotropy, and microvascular perfusion. However, the role of dMRI in characterizing different aspects of bone quality, especially in aging and osteoporosis, has not yet been fully established, particularly in clinical applications. The reason lies in the complications accompanied with implementation of dMRI in assessment of human bone structure, in terms of acquisition and quantification. Bone is a composite tissue comprising different elements, each contributing to the overall quality and functional competence of bone. As diffusion is a critical biophysical process in biological tissues, early changes of tissue microstructure and function can affect diffusive properties of the tissue. While there are multiple MRI methods to detect variations of individual properties of bone quality due to aging and osteoporosis, dMRI has potential to serve as a superior method for characterizing different aspects of bone quality within the same framework but with higher sensitivity to early alterations. This is mainly because several properties of the tissue including directionality and anisotropy of trabecular bone and cell density can be collected using only dMRI. In this review article, we first describe components of human bone that can be potentially detected by their diffusivity properties and contribute to variations in bone quality during aging and osteoporosis. Then we discuss considerations and challenges of dMRI in bone imaging, current status, and suggestions for development of dMRI in research studies and clinics to segregate different contributing components of bone quality in an integrated acquisition. Level of Evidence: 5 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:975-992., (© 2019 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Statistical models (SMs) of shape (SSM) and appearance (SAM) have been acquiring popularity in medical image analysis since they were introduced in the early 1990s. They have been primarily used for segmentation, but they are also a powerful tool for 3D reconstruction and classification. All these tasks may be required in the osteoporosis domain, where fracture detection and risk estimation are key to reducing the mortality and/or morbidity of this bone disease. In this article, we review the different applications of SSMs and SAMs in the context of osteoporosis, and it concludes with a discussion of their advantages and disadvantages for this application.

The risk of osteoporotic fracture is inversely related to bone mineral density (BMD), but how spatial BMD pattern influences fracture risk remains incompletely understood. This study used a pixel‐level spatiotemporal atlas of proximal femoral BMD in 13,338 white European women (age 20–97 years) to quantitate age‐related texture variation in BMD maps and generate a "reference" map of bone aging. We introduce a new index, called Densitometric Bone Age (DBA), as the age at which an individual site‐specific BMD map (the proximal femur is studied here) best matches the median aging trajectory at that site in terms of the root mean squared error (RMSE). The ability of DBA to predict incident hip fracture and hip fracture pattern over 5 years following baseline BMD was compared against conventional region‐based BMD analysis in a subset of 11,899 women (age 45–97 years), for which follow‐up fracture records exist. There were 208 subsequent incident hip fractures in the study populations (138 femoral necks [FNs], 52 trochanteric [TR], 18 sites unspecified). DBA had modestly better performance compared to the conventional FN‐BMD, TR‐BMD, and total hip (TOT)‐BMD in identifying hip fractures measured as the area under the curve (AUC) using receiver operating characteristics (ROC) curve analysis by 2% (95% confidence interval [CI], −0.5% to 3.5%), 3% (95% CI, 1.0% to 4.0%), and 1% (95% CI, 0.4% to 1.6%), respectively. Compared to FN‐BMD T‐score, DBA improved the ROC‐AUC for predicting TR fractures by ~5% (95% CI, 1.1% to 9.8%) with similar performance in identifying FN fractures. Compared to TR‐BMD T‐score, DBA improved the ROC‐AUC for the prediction of FN fractures by ~3% (95% CI, 1.1% to 4.9%), with similar performance in identifying TR fractures. Our findings suggest that DBA may provide a spatially sensitive measure of proximal femoral fragility that is not captured by FN‐BMD or TR‐BMD alone. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]