The application of engineering theory and analysis to bone has led to many insights regarding the etiology of increased skeletal fragility with aging and diseases such as osteoporosis. According to mechanics of materials theory, whole bone mechanical behavior should depend on the amount of bone tissue, bone geometry, and tissue material properties. Through the use of micro-computed tomography, the influence of bone mass and geometry on whole bone strength and stiffness have been confirmed and quantified. With the application of nanoindentation to the study of bone, the ability to measure the mechanical properties of bone at the micron length scale is now possible. However, most studies using nanoindentation have focused only on tissue-level properties and, therefore, relatively little is known about the relationships between tissue-level properties and whole bone mechanical behavior. The objectives of this research were to 1) examine the effects of two composition changes, mineralization and crystallinity, on whole bone and tissue-level mechanical behavior, and 2) examine changes in tissue-level composition and mechanical properties due to osteoporosis.

To investigate the effects of mineralization and crystallinity independently, two separate dietary interventions in rodents were used. First, vitamin D deficiency in growing rats was used to reduce cortical bone mineralization. The vitamin D deficient animals had compromised whole bone mechanical behavior, as indicated by the lower failure moment and bending stiffness. To take into account the mechanical property heterogeneity and cortex geometry when predicting whole bone mechanical behavior, a density-weighted section modulus was calculated using composite beam theory. The weighted section moduli predicted whole bone mechanical behavior better than geometric parameters or average mechanical properties alone.

In the second study, growing rats given fluoride had increased cortical bone crystallinity and reduced measures of whole bone mechanical behavior. Cortical cross-sectional geometry was not different with fluoride, implying a difference in mechanical properties was responsible for the altered whole bone mechanical behavior;​ however, indentation modulus and hardness were not different. The discrepancies between tissue-level and whole bone mechanical behavior suggest that interfaces between microstructural features and other mesoscale features influence whole bone mechanical behavior.

In the third study, tissue-level composition and mechanical properties of osteoporotic cancellous bone from a fracture prone location were examined. Vertebral cancellous bone from female cadavers was divided into two groups, osteoporotic and not osteoporotic based on T-scores from dual-energy x-ray absorptiometry scans. Tissue from osteoporotic donors had lower indentation moduli and showed a trend towards being less mineralized compared to tissue from normal and osteopenic individuals. Independent of reduced bone mass and altered trabecular architecture, lower indentation moduli of osteoporotic bone could contribute to skeletal fragility associated with osteoporosis.