Influence of the ultrastructure on the fracture characteristics of human bone in physiological and pathological conditions

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Disease- and aging-related changes to the musculoskeletal system are known to increase its susceptibility to fracture. Such changes are especially critical in the elderly as the consequent fractures can lead to restrictions on quality of life as well as significant mortality. Traditional thinking on the deterioration of bone with aging and disease has focused predominantly on the question of bone quantity, which is currently used as a predictor of fracture risk in clinical settings. However, the increased fracture risk of bone with aging and disease is not solely dependent on bone quantity; indeed, the fracture resistance is additionally affected by both morphological and compositional changes, which describe the bone quality. Understanding how the nature of fracture is affected by bone quality requires characterization of the compositional and morphological features at each level of bone’s complex hierarchical structure, which has characteristic features from millimeter to nanometer levels, specifically evolving to its macroscopic form (>3 mm) from a nanostructure comprised of collagen and mineral (<500 nm) and a microstructure of lamellae, osteocyte lacunae (3-20 μm) and osteons (100-300 μm). We believe that a hierarchical characterization of aged and diseased bone will lead to a greater understanding of how these conditions cause an increase in fracture risk.We will use an integrated approach combining bone quality assessment techniques by using microcomputed tomography, synchrotron small-angle X-ray scattering/wide-angle X-ray scattering, backscattered electron imaging, deep ultraviolet Raman/Fourier transform infrared spectroscopy, high-performance liquid chromatography and enzyme-linked immunosorbent assay to characterize various levels of the hierarchical structure of skeletally intact and diseased bones. In this connection, we would like to address whether the ultrastructure in terms of the collagen and mineral’s characteristics is significantly altered in bone diseases, whether there are distinct changes in structural and material characteristics (e.g., inter- and intrafibrillar crosslinking), and how these changes can affect the mechanisms of fracture and hence the bone strength and toughness. Our hypothesis is that the primary mechanisms influencing fracture resistance in bone can be associated with the plasticity mechanisms of mineralized collagen fibril sliding at the nanoscale, fracture path properties at the microscale, and microcracking at both scales. Our aim is to provide new information on how distinct ultrastructural features affect the mechanical behavior of bone tissue. Additionally, as this is a departure from traditional bioengineering and medical studies of bone fracture, we hope that such materials-science-based studies can positively impact the medical field by providing new and different insights into bone-related diseases, and as such can help in the search for new cures and treatment options for bone diseases.