The mechanical properties of trabecular bone have been shown to vary significantly with age, anatomic location, and metabolic condition. Efforts towards predicting its behavior have been extensive, and significant relationship between measures of density and mechanical integrity have been reported. Unfortunately, the significant heterogeneity in trabecular bone anisotropy contributes to significant unexplained variance in its strength and modulus when predicted using scalar measures of mass or density. As a result, numerous investigators have attempted to include measures of architecture in an effort to more rigorously investigate potential physiologic optimization strategies, as well as account for the increased fragility associated with advancing age. In our laboratories we have utilized a unique three-dimensional, microcomputed tomography system to measure trabecular plate thickness, trabecular plate separation, trabecular plate number, surface to volume ratio, bone volume fraction, anisotropy, and connectivity in isolated specimens of trabecular bone. The results of these studies demonstrate that in normal bone, more than 80% of the variance in its mechanical behavior can be explained by measures of density and orientation. The independent measures of connectivity and trabecular plate number were found to be significantly correlated with bone volume fraction, suggesting a potential strategy in the formation of trabecular bone. It might be hypothesized, however, that the relationship between bone volume fraction and connectivity may be substantially altered under conditions associated with aging, fragility, or metabolic bone disease. This hypothesis would be consistent with the histologic evidence of reduced connectivity in osteopenic patients.