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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The effect of advanced glycation endproduct accumulation on bone

Van Vliet, Miranda 13 July 2017 (has links)
Diabetes is associated with increased fracture risk, which leads to increased morbidity and eventual mortality with a substantial financial burden. Type 2 Diabetics also have increased fracture risk, despite having the same or higher BMD as non-diabetics with a low fracture risk. One hypothesis for this is increased modifications made to the extra-cellular matrix via non-enzymatic glycation (NEG) that can occur in a hyperglycemic environment, such as with diabetes. The accumulation of NEG products, known as advanced glycation endproducts (AGEs) can possibly lead to microdamage and eventual weakening of the bone itself. We developed a time-response model in order to induce a wide range of AGEs in a manner that would sustain the mineral integrity of the bone and could be applied to a variety of bone sample types. This was performed on 65 rat tibias, distributed amongst 8 groups (3,7,10, & 14 days) for both ribose and control. Secondly, the protocol was performed on human cortical beam samples cut from 10 donor tibias with 3,5 and 7 day time points for ribose and control groups. All samples were incubated in a 0.6 M ribose solution or 0.0 M ribose control solution. There was a 7, 4, and 5-fold increase in AGEs at the 7, 10, and 14 day time points respectively over controls in the rat tibia study. There was no significant variation in cortical porosity, however TTMD was significantly less dense in the 14-day ribose treated groups. There was a trend toward higher AGEs with time in the human cortical beam specimens, but no significant increase. The AGEs values in the human cortical beam specimens were much lower than expected based on previous trials and reports in the literature. We were able to establish a time-response model for AGE accumulation in bone. However, the effects of AGEs on bone material properties remains inconclusive.
2

Exploring the Utility of Several Evaluation Methods in Distinguishing Cannon Bones from Fracture-Afflicted and Skeletally Intact Racehorses

Jonathan Elliot Gaide (7878704) 06 December 2019 (has links)
Stress fractures are common in the limb bones of human and equine athletes alike. Repetitive skeletal loading can lead to remodeling and the accumulation of microdamage in bone, which only becomes grossly evident during catastrophic fracture of the bone due to the accumulated microdamage. Though various metrics attempting to quantify bone health exist, none have distinguished themselves as early predictors of the susceptibility of bone to fracture. In this exploratory study, we examine the ability of several evaluation methods to distinguish between third metacarpal (MC3) bones from racehorses that have experienced a limb-bone fracture and from those that have not. Third metacarpal bones were harvested from deceased Thoroughbred racehorses and categorized into four groups: MC3 bones from horses whose cause of death was not related to skeletal fracture (Control group, n = 20), MC3 bones form horses that were euthanized after fracturing proximal sesamoid bones (Sesamoid group, n = 20), MC3 bones from horses that were euthanized after fracturing a non-MC3 long bone (Long Bone group, n = 19), and MC3 bones from horses that were euthanized after fracturing an MC3 (MC3 group, n = 5). Each MC3 bone underwent testing using a variety of tools and methods at the proximal, midshaft, and distal levels of the lateral, dorsal, and medial surfaces. All tools and methods (OsteoProbe reference point indentation, BioDent reference point indentation, x-ray, micro-CT, and pQCT) exhibited some capability in differentiating between control and fracture groups. The long-term objective of this project is to create a model that will utilize data from a set of evaluations and output the susceptibility of the horse to fracture a bone, a long bone, or the MC3, specifically. Although the sample size in this study is not sufficient to create a reliably predictive logistic regression model, promising results from preliminary models provide incentive to further explore the possibility of creating one. While clinical practicality will be a vital consideration for a model in the future, establishing this basis for the capability of each evaluation at hand is a necessary first step in predicting and preventing fracture in bone.
3

Multi-scale analysis of morphology, mechanics, and composition of collagen in murine osteogenesis imperfecta

Bart, Zachary Ryan 06 November 2013 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Osteogenesis imperfecta is a rare congenital disease commonly characterized by brittle bones caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The murine model (oim) exists as a natural mutation of this protein, converting its heterotrimeric structure of two Col1a1 molecules and a single Col1a2 molecule into homotrimers composed of only the former. This defect impacts bone mechanical integrity, greatly weakening their structure. Femurs from male wild type (WT), heterozygous (oim/+), and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanometer scale that may partially attribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure through the use of µ-Computed Tomography and Raman spectroscopy respectively indicate a smaller, brittle phenotype caused by oim. Changes within the periodic D-spacing of collagen point towards a reduced mineral nucleation site, supported by reduced mineral crystallinity, resulting in altered material and structural behavior in oim/oim mice. Multi-scale analyses of this nature offer much in assessing how molecular changes can compound to create a degraded, brittle phenotype.

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