Osteoporosis is a major public health threat for millions of Americans with billions of dollars per year of national direct costs for osteoporotic fractures. Osteoporosis results in a decrease in overall bone mass and subsequent increase in the risk of bone fracture. Bone strength arises from the combination of bone size and shape, the distribution of bone mass throughout the structure, and the quality of the bone material. Advances in medical imaging have enabled a comprehensive assessment of bone structure through the analysis of high-resolution scans of relevant anatomical sites, eg, the proximal femur. However, conventional imaging analysis techniques use predefined regions of interest that do not take full advantage of such scans. Recently, computational anatomy, a set of imaging-based analysis algorithms, has emerged as a promising technique in studies of osteoporosis. Computational anatomy enables analyses that are not biased to one particular region and provide a more complete assessment of the whole structure. In this article, we review studies that have used computational anatomy to investigate the structure of the proximal femur in relation to age, fracture, osteoporotic treatment, and spaceflight effects.