Osteoporosis is a disease characterized by loss of bone mass and structural deterioration leading to increased risk of fracture. Currently, osteoporosis is assessed by areal bone mineral density;​ however, this does not provide structural information, which is a key determinant of bone strength. Recent advances allow for the assessment of bone structure in vivo using quantitative computed tomography (QCT) and high-resolution peripheral QCT (HR-pQCT). The overall objective of this thesis was to improve the assessment of bone structure and strength using three-dimensional imaging technologies.

First, measurements of cortical porosity from HR-pQCT were validated against micro-CT (R2 = 0.80) and applied to a population-based sample (N = 280, Ages:​ 18-99 yrs.) of healthy, osteopenic, and osteoporotic, pre- and postmenopausal women. Cortical porosity was higher in postmenopausal women and those with disease. Measurements of cortical porosity were also applied to another group with high fracture incidence:​ children and adolescents (N = 398, Ages:​ 9-22 yrs.). Boys were found to have higher porosity than girls, and those at earlier pubertal stages had higher porosity than those post-pubertal.

Bone quality measurements were also combined with finite element estimates of bone strength to determine if the measurements could distinguish women with fracture from fracture-free controls. High accuracy was achieved using both HR-pQCT scans of peripheral sites (83.3%) and QCT scans of the proximal femur (84.3%) when classifying the groups using support vector machines.

Together, these results provide insight into the differences in bone microstructure and strength with age and disease. In addition, this work demonstrates the ability of novel 3D technologies and methods to better discriminate individuals with and without fracture.