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. Although men experience loss of bone mass with age, osteopenic changes in women occur at an earlier age and accelerate when estrogen’s bone-protective effects diminish after menopause. Consequently, 3 out of 4 fragility fractures occur in women. To preserve bone mass and reduce fracture risk, therapeutics which alter the morphology of bone are prescribed to atrisk patients. The most commonly prescribed drug to prevent osteoporotic bone fracture is alendronate, a bisphosphonate which increases 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. The effects of aging, sex, and alendronate treatment on microdamage initiation of linear, diffuse, and severe morphologies were investigated in trabecular bone. With the use of micro-computed tomography at high resolution, estimations of the stress/strain environment of individual trabeculae within the trabecular lattice were obtained with finite element modeling. Calcium-chelating fluorophores were used to fluorescently label damage in bone, and stress and strain values of trabeculae were linked to observed damage morphologies resulting from mechanical loading. Across all studies, microdamage morphology was highly associated with the stress/strain magnitude on damaged trabeculae. Furthermore, thinner, rod-like trabeculae oriented along the loading axis were most likely to develop severe damage in all studies.

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 extended 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.