Fracture, aging, and disease in bone

Abstract

From a public health perspective, developing a detailed mechanistic understanding of the well-known increase in fracture risk of human bone with age 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-/nano-structural 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 pico-force atomic-force microscopy, nanoindentation and 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 crackgrowth 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 TGF-β can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease. *

Age-related changes in the plasticity and toughness of human cortical bone at multiple length scales

“…In human cortical bone, cross-links occur in two forms: (i) enzymatic crosslinks-as immature intrafibrillar (dehydrodihydroxynorleucine and dehydrohydroxylysinonorleucine) and mature interfibrillar (pyridinoline and pyrrole), and (ii) nonenzymatic advanced glycation end products (AGEs), such as pentosidine, that form both intra-and interfibrillar links along the collagen backbone (16). Although the level of enzymatic cross-links stabilizes around 10-15 y of age (17,18), AGEs can increase up to fivefold with age (15,18,19), which has been correlated to reduced bone toughness and fracture resistance (20)(21)(22)(23). Similarly, excessive remodeling with age increases the osteonal density in human cortical bone; this governs the degree of microcracking and in turn affects the development of crack bridges, which provide a major source of toughening at micrometer-scale levels and above (12).…”

Temperature Effect on Hydroxyapatite Preparation by Co-precipitation Method under Carbamide Influence

“…The length between 30 to 60 μm, about 40 microns, the average length of about 2 to 4 microns wide, length to diameter ratio between 10 to 20. [15] Figure 3 is the infrared spectrum of sample f. Seen from the image, there are several characteristic peaks. The absorption peaks at 561 cm -1, 960 cm-1 , 603 cm -1 are the PO43 -characteristics vibration peak; at 871 cm -1 is the HPO42-characteristics vibration peak; at 1450 cm -1 belongs to the characteristics infrared spectrum(type B replace) of CO32- [14]; OH -is shown by the characteristic of vibration peak at 1310 cm -1 without 3570 cm -1.…”

Quantitative X-ray tomography

“…315 While a great deal of the work to date has been focussed on metals and alloys, CT analyses of crack propagation are becoming more widespread in other areas, particularly with respect to more complex structured materials including 2D and 3D composite systems, 103,291,316 self-healing systems 111,317 and crack propagation in natural materials, e.g. bone, [318][319][320] teeth, 321 wood, 268 as well as graphite, 322 which is an important structural material for the nuclear industry. Mostafavi et al 323 found from surface DIC that unstable fracture is preceded by the sub-critical propagation of surface cracks having a scale similar to the microstructure.…”