? Osteoporosis has been defined traditionally as porous bone structure that is reduced in quantity but has normal bone material or quality. A decrease in bone density is considered the hallmark of osteoporosis, but bone fracture is the critical clinical outcome. Moreover, although bone density is associated with the mechanical characteristics of bone, it does not fully account for bone mechanical response. There is a growing body of evidence that bone turnover contributes to changes in bone strength by affecting not only quantity but also architecture, mineral, and matrix quality. Quantitative micro-computed tomography (microCT) has the potential to characterize the quantity and quality of cancellous bone in three dimensions and to explore the effects of osteoporosis and bone turnover. The goal of this exploratory & developmental grant proposal (R21) is to analyze human biopsies using quantitative microCT. Iliac crest biopsies characterized as normal, low-turnover osteoporosis, and high-turnover osteoporosis will be examined to test the following research question: Do cancellous volume fraction, trabecular three-dimensional architecture, and patterns of material inhomogeneity differ among normal, low-turnover, and high-turnover osteoporotic bone? Human iliac crest biopsies of low-turnover or high-turnover osteoporosis will be compared with normal biopsies by quantitative microCT. Bone volume fraction and trabecular architecture will be characterized. Quantitative CT x-ray attenuation values will be used to provide tissue mineral density within trabeculae. The variation in tissue mineral density will be assessed as a function of depth from the trabecular surface by a distance transformation approach. Comparisons will be made among the three groups to investigate whether substantial differences exist between low- and high-turnover bone and between osteoporotic and control specimens. The main goal is to detect differences in trabecular architecture and material properties with turnover state. These results should lead to specific hypotheses about the effects of turnover rate on bone quality in osteoporosis and possibly under therapeutic interventions. ? ?
