Bone is a composite material consisting of hydroxyapatite crystals deposited in an oriented manner on a collagen backbone. The arrangement of the mineral and organic phases provides bone tissue with the appropriate strength, stiffness, and fracture resistance properties required to protect vital internal organs and maintain the shape of the body. A remarkable feature of bone is the ability to alter its properties and geometry in response to changes in the mechanical environment. However, in cases of metabolic bone diseases or aging, bone can no longer successfully adapt to its environment, increasing its fragility. To elucidate the mechanisms of bone microdamage, this research project developed a specimen-specific approach that integrated 3D imaging, histological damage labeling, image registration, and image-based finite element analysis to correlate microdamage events with microstructural stresses and strains under compressive loading conditions. By applying this novel method to different ages of bovine and human bone, we have shown that the local mechanical environment at microdamage initiation is altered with age. We have also shown that formation of microdamage is time-dependent and may have implications in age-related microdamage progression with cyclic and/or sustained static loading. The work presented in this dissertation is significant because it improved our understanding of trabecular bone microdamage initiation and unlocked exciting future research directions that may contribute to the development of therapies for fragility diseases such as osteoporosis.

Skeletal fragility is characterized by low bone mass, negative changes in bone microarchitecture, and compromised tissue matrix properties, including accumulation of microdamage. Microdamage accumulates in vivo from daily physiological loading and is targeted for repair through a normal remodeling process, thus preventing microcrack growth and potential fracture. However, impaired remodeling is associated with aging and osteoporosis, resulting in an increased accumulation of microdamage which contributes to reduced bone mechanical properties. The current clinical method for assessing increased risk of fracture involves measuring bone mineral density (BMD) of the hip and spine, locations of trabecular bone where high rates of remodeling occur. The bisphosphonate alendronate (ALN) reduces clinical risk for fracture by significantly increasing BMD, but studies have shown a concomitant reduction in intrinsic properties that may be the underlying cause for recent reports of spontaneous fractures with long-term alendronate use. Another anti-resorptive agent called raloxifene (RAL) is a selective estrogen receptor modulator (SERM) and has been shown to modestly improve BMD while decreasing fracture risk to a similar degree as alendronate. The combination of RAL and ALN as a treatment for osteoporosis may provide the benefits of each drug without the negative effects of ALN. Therefore, the overall goal of this thesis was to address the effects of aging and anti-resorptive agents on the properties of bone through the formation of microdamage. Assessment of age-related effects on bone was conducted through quantification of microdamage progression. It was found that old bone results in greater incidences of microdamage progression, reflecting a compromised tissue matrix with reduced resistance to crack growth. Effects of combination treatment with RAL and ALN were evaluated through biomechanical testing, micro-CT imaging, and microdamage quantification. Results showed improved trabecular bone volume and ultimate load with positive effects on trabecular architecture. Combination treatment reduced the proportion of microdamage that may lead to catastrophic fracture, indicating an improvement in the local tissue matrix properties.

One indication of increasing fragility of bone is the accumulation of microscopic cracks, or microdamage, within the bone matrix. Microdamage accumulates in bone of the elderly, when changes in bone material properties and matrix architecture coupled with a decrease in bone repair mechanisms compromise bone integrity. To preserve bone mass and reduce fracture risk, therapeutics such as alendronate are prescribed which increase bone volume fraction by decreasing the rate of bone turnover. However, concerns over adverse effects of prolonged turnover suppression have been reinforced by findings of increased microdamage density with alendronate use. Microdamage formation is not always pathologic, but extensive accumulation of damage can be an indicator of reduced bone quality. The work in this thesis explores the hypothesis that microdamage in bone of lower quality will form more easily and progress more extensively than in bone of higher quality. Microdamage initiation stresses and strains were obtained for trabecular bone from older females, older males, and younger females to determine whether thresholds for damage initiation were lower in older females. Results suggest that the stress threshold for damage initiation in older females may indeed be lower compared with younger females, and that normalized strain thresholds for severe damage formation in older males may be decreased compared with older females. Damage propagation was evaluated as a function of age and sex to determine whether damage in older women progressed more extensively than in younger women or men. Results suggest that bone from older individuals had decreased resistance to crack propagation evidenced by an increased number of severely damaged trabeculae which expanded in area under cyclic loading; however no sex differences were uncovered. Finally, the stress/strain thresholds for damage initiation were investigated in alendronate-treated bone, and results indicate that a decreased stress threshold was needed to initiate damage formation of a linear and severe morphology after one year of treatment. After three years of treatment, however, micromechanical properties recovered, perhaps due to increased matrix mineralization which increased tissue level stiffness.

Le but principal de cette thèse est de développer un modèle numérique pour modéliser les phénomènesde bifurcation et du branchement des fissures. Pour réaliser cet objectif, il était indispensablede posséder un modèle permettant un couplage fort entre le modèle de Plasticité cristalline etcelui de l'Endommagement régularisé. Dans un premier temps, quelques outils de post-traitement ont été développés pour analyser les systèmes de glissement actifs. Ces outils ont été utilisés surdes simulations d'éprouvettes réelles, et comparés à des résultats expérimentaux. Par ces comparaisons, l'application du modèle de Plasticité cristalline aux superalliages monocristallins a été validée. Ce modèle a ensuite été couplé avec le modèle d'endommagement régularisé. Le couplage a été réalisé dans les deux sens, c'est-à-dire que l'évolution de la plasticité a une influence sur l'endommagement et vice-versa. Le nouveau modèle peut être implémenté simplement, avec la méthode traditionnelle des Éléments Finis. Des expériences étudiant la propagation de fissure sous des chargements de types différents ont été simulées à l'aide de ce nouveau modèle :éprouvettes CT,fissuration en Mode II et rupture en fluage. Une méthode pour l'identification des paramètres matériaux a également été proposée. / The main goal of this dissertation was to develop a model to simulate the processes of crack bifurcation and crack branching in anisotropic materials. To achieve this goal, a thorough coupling of crystal plasticity and regularised damage models was deemed necessary. Firstly, post-processing tools were developed to better analyse the results obtained from standard Crystal Plasticity simulations. These were then compared with experiments, thereby validating the use of Crystal Plasticity models for Nickel base single crystal superalloys. The validated Crystalplasticity model was then coupled with a regularised microdamage model such that the evolution of plasticity influenced damage and vice versa. The newly developed model allows for the simulation of cracks using the standard Finite Element Approach. Experiments studying crack propagation under different types of loads were simulated using the newly developed model, including CT, shear andcreep specimens. A methodology was also proposed for the identification of the newly introduced material parameters.