Susceptibility of aging human bone to mixed-mode fracture increases bone fragility

George, W.T.; Vashishth, Deepak

doi:10.1016/j.bone.2005.08.002

Cited by 33 publications

(17 citation statements)

References 36 publications

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“…The microcracks in our experiments exhibited dimensions (lengths up to 700 μm and widths of about 3 μm) also generated during in vivo experiments from various groups. George and Vashishth [38] generated linear microcracks of up to 300 μm length and 8 μm width by conducting fatigue tests on human cortical bone specimens. Burr et al [2, 22] and Kennedy et al [39] investigated microcracks with lengths of 200–800 μm and widths of 6–10 μm in canine femurs and human bones, respectively.…”

Section: Discussionmentioning

confidence: 99%

Microcracks and Osteoclast Resorption Activity In Vitro

et al. 2012

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During bone remodeling osteoclasts resorb bone, thus removing material, e.g., damaged by microcracks, which arises as a result of physiological loading and could reduce bone strength. Such a process needs targeted bone resorption exactly at damaged sites. Osteocytic signaling plays a key role in this process, but it is not excluded that osteoclasts per se may possess toposensitivity to recognize and resorb damaged bone since it has been shown that resorption spaces are associated with microcracks. To address this question, we used an in vitro setup of a pure osteoclast culture and mineralized substrates with artificially introduced microcracks and microscratches. Histomorphometric analyses and statistical evaluation clearly showed that these defects had no effect on osteoclast resorption behavior. Osteoclasts did not resorb along microcracks, even when resorption started right beside these damages. Furthermore, quantification of resorption on three different mineralized substrates, cortical bone, bleached bone (bone after partial removal of the organic matrix), and dentin, revealed lowest resorption on bone, significantly higher resorption on bleached bone, and highest resorption on dentin. The difference between native and bleached bone may be interpreted as an inhibitory impact of the organic matrix. However, the collagen-based matrix could not be the responsible part as resorption was highest on dentin, which contains collagen. It seems that osteocytic proteins, stored in bone but not present in dentin, affect osteoclastic action. This demonstrates that osteoclasts per se do not possess a toposensitivity to remove microcracks but may be influenced by components of the organic bone matrix.

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Section: Discussionmentioning

confidence: 99%

Microcracks and Osteoclast Resorption Activity In Vitro

et al. 2012

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“…Cyclic loading induced damage accumulation is also reported to weaken vertebrae (Burr et al, 1997) and is often associated with loosening of implants (Bauer and Schils, 1999). Whereas the fatigue strength of cortical bone is extensively reported in the literature (Carter et al, 1981;Zioupos and Casinos, 1998;Yeni and Fyhrie, 2002;O'Brien et al, 2003;Taylor et al, 2003;George and Vashishth, 2006) few data are available for trabecular bone (Moore and Gibson, 2003;Haddock et al, 2004;Yamamoto et al, 2006;Dendorfer et al, 2006). Most studies concentrate on bovine and human trabecular bone specimens cored in the main (onaxis) direction and analysed in cyclic compression.…”

Section: Introductionmentioning

confidence: 93%

Anisotropy of the fatigue behaviour of cancellous bone

Dendorfer

Maier

Taylor

et al. 2008

Journal of Biomechanics

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“…Observed changes in physiologic function include loss of pigments in the hair, wrinkling of the skin, bone fragility [2], muscle atrophy [3], brain atrophy [4], cancer [5-7] and organ dysfunction [8]. An increase in oxidative stress with age has been implicated to be at the root of many of these age-related physiologic declines and is the basis for the free radical theory of aging as presented by Denham Harman in 1956 [9].…”

Section: Introductionmentioning

confidence: 99%

Mouse Models of Oxidative Stress Indicate a Role for Modulating Healthy Aging

Hamilton¹,

Walsh

Remmen³

2012

J Clin Exp Pathol

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Aging is a complex process that affects every major system at the molecular, cellular and organ levels. Although the exact cause of aging is unknown, there is significant evidence that oxidative stress plays a major role in the aging process. The basis of the oxidative stress hypothesis is that aging occurs as a result of an imbalance between oxidants and antioxidants, which leads to the accrual of damaged proteins, lipids and DNA macromolecules with age. Age-dependent increases in protein oxidation and aggregates, lipofuscin, and DNA mutations contribute to age-related pathologies. Many transgenic/knockout mouse models over expressing or deficient in key antioxidant enzymes have been generated to examine the effect of oxidative stress on aging and age-related diseases. Based on currently reported lifespan studies using mice with altered antioxidant defense, there is little evidence that oxidative stress plays a role in determining lifespan. However, mice deficient in antioxidant enzymes are often more susceptible to age-related disease while mice overexpressing antioxidant enzymes often have an increase in the amount of time spent without disease, i.e., healthspan. Thus, by understanding the mechanisms that affect healthy aging, we may discover potential therapeutic targets to extend human healthspan.

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Susceptibility of aging human bone to mixed-mode fracture increases bone fragility

Cited by 33 publications

References 36 publications

Microcracks and Osteoclast Resorption Activity In Vitro

Microcracks and Osteoclast Resorption Activity In Vitro

Anisotropy of the fatigue behaviour of cancellous bone

Mouse Models of Oxidative Stress Indicate a Role for Modulating Healthy Aging

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