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From a public health perspective, developing a detailed mechanistic understanding of the well-known increase with age in fracture risk of human bone is essential. This also represents a challenge from materials science and fracture mechanics viewpoints. Bone has a complex, hierarchical structure with characteristic features ranging from nanometer to macroscopic dimensions; it is therefore significantly more complex than most engineering materials. Nevertheless, by examining the micro-/nanostructural changes accompanying the process of aging using appropriate multiscale experimental methods and relating them to fracture mechanics data, it is possible to obtain a quantitative picture of how bone resists fracture. As human cortical bone exhibits rising ex vivo crack-growth resistance with crack extension, its fracture toughness must be evaluated in terms of resistance-curve (R-curve) behavior. While the crack initiation toughness declines with age, the more striking finding is that the crack-growth toughness declines even more significantly and is essentially absent in bone from donors exceeding 85 years in age. To explain such an age-induced deterioration in the toughness of bone, we evaluate its fracture properties at multiple length scales, specifically at the molecular and nano dimensions using vibrational spectroscopies, at the microscale using electron microscopy and hard/soft x-ray computed tomography, and at the macroscale using R-curve measurements. We show that the reduction in crack-growth toughness is associated primarily with a degradation in the degree of extrinsic toughening, in particular involving crack bridging, and that this occurs at relatively coarse size scales in the range of tens to hundreds of micrometers. Finally, we briefly describe how specific clinical treatments, e.g., with steroid hormones to treat various inflammatory conditions, can prematurely damage bone, thereby reducing its fracture resistance, whereas regulating the level of the cytokine Transforming Growth Factor-β can offer significant improvements in the stiffness, strength, and toughness of bone and as such may be considered a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.
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