Early identification of fracture risk, most commonly caused by osteoporosis induced bone fragility, is important in implementing appropriate treatment and preventive strategies. Current diagnostic modalities focus on measuring bone mineral density (BMD), but several lines of clinical evidence show that measuring BMD alone is not sufficient for identifying those at risk for fractures. In fact, the quality of bone (its strength or resistarice to fracturing) is affected not only by bone quantity (BMD), but also by its microarchitecture and material (tissue) properties. This dissertation serves two important goals with regard to these issues. The first is to comprehensively characterize the relative influence of microstructure and material properties to understand their respective influence on bone quality. Secondly, it evaluates the ability of micro-finite element methods, incorporating microstructure and material properties, to non-invasively assess apparent bone strength.

The inclusive nature of this project required a number of interdisciplinary techniques to fully analyze the bone, including high resolution micro-CT scanning to evaluate microstructure, traditional DEXA scanning to calculate BMD, materials testing to assess apparent mechanical properties, nanoindentation testing to evaluate tissue nanomechanical properties, and linear elastic finite element modeling to virtually derive apparent mechanical properties. The trabecular bone samples used came from sheep distal femora, and human calcanei and vertebral bodies.

The trabecular microstructure (in particular volume fraction and the structural model index) correlated significantly with apparent bone modulus and strength ~ either as well as or better than BMD alone. Analysis of the trabecular tissue showed that while there was a great amount of variability in the local elastic modulus and hardness, the average tissue modulus of each specimen showed very little variability across samples within a species. Moreover, there were no significant correlations between tissue and apparent mechanical properties. Apparent modulus values derived from micro-finite element modeling, however, correlated highly to empirically measured mechanical properties even using only homogeneously distributed materia! properties.

In summary, these findings suggest that trabecular architectural properties are more important than tissue modulus in determining apparent mechanical strength. Also, micro-finite element models, based upon high-resolution imaging, provide a powerful method to directly and non-invasively assess bone quality.