Advances in our understanding of age related bone fragility, computational modeling and adaptation have emphasized the need to characterize bone properties at a tissue level. Morphologically, trabecular and cortical tissue appear to have significantly different properties. Human cortical bone is composed primarily of osteons of concentric lamellae, while trabecular bone tissue is characterized by a mosaic of angular segments of parallel sheets of lamellae. Trabecular tissue may be less mineralized than cortical tissue and data suggest that trabecular bone is much more active in remodeling and turnover. Recent data describing the mechanical properties of cortical or trabecular tissue have presented conflicting results. Experimental and computational methods have been developed to quantify the tissue modulus of individual trabeculae including buckling, uniaxial tension, three or four point bending, ultrasound and finite element calculations. The modulus of trabecular tissue has been reported to range from 1-14 GPá:​ This large variation in modulus values may be the result of testing methods, or perhaps, microstructural or mineral content differences. The most recent data, however, present an emerging consensus that trabecular tissue is 20-30% less stiff than cortical bone tissue. The data also indicate that tissue mineral density alone cannot explain the measured variance in modulus values, suggesting a significant dependence on microstructural features (lacunae, cement lines, etc.). The results from fatigue experiments of both trabecular and cortical bone tissue demonstrate that cortical bone tissue has higher fatigue resistance than trabecular bone tissue, probably due to the differences in tissue morphology. This finding may emphasize the importance of tissue ultrastructure in damage accumulation. Preliminary data on trabecular and cortical tissue from vertebral bodies have demonstrated a significant age-related variation in tissue modulus and higher values in cortical tissue when compared to trabecular tissue. Continuing studies are focused on quantifying the tissue microstructure and correlating these measures to physical properties measured utilizing nanoindentation and fatigue experiments in an effort to more clearly delineate structure-function relationships in bone tissue and potential implications in age-related bone fragility and adaptation.