We have recently developed x-ray computed tomography methods to accurately measure the regional bone mineral density (rBMD) within small volumes (.004cc) of individual vertebra and produce detailed (n = 655,360), three dimensional mappings of vertebral rBMD for human submects. Compared to previous computed tomography methods, which assay the bone mineral density within single large volumes, the regional method produces a complete description of the spatial distribution of bone material in a vertebra. Our preliminary results indicate that vertebral cancellous bone is distributed with varied, non-uniform patterns within the vertebral body. The objective of the proposed research is to characterize in-vivo vertebral bone architecture based on measured rBMD and evaluate the hypothesis that changes in bone architecture associated with metabolic bone disease are of importance in the pathogenesis of vertebral fractures. Specifically we wish to improve our ability to characterize measured rBMD data, evaluate the vertebral rBMD characteristics of asymptomatic volunteers and subjects with minimal osteoporotic disease, establish whether vertebral bone loss occurs with regional variations, and measure the relationship between rBMD and the mechanical properties of in-vivo specimens. Overall, the proposed research involves measurements of vertebral rBMD on 800 new in-vivo vertebrae (data has already been acquired on 200) and 336 measurements on in-vitro specimens. The bone architecture of each vertebra will be described by 31 parameters computed from the detailed, three dimensional mapping of rBMD.