Date of Award

Spring 1-1-2011

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Mechanical Engineering

First Advisor

Virginia L. Ferguson

Second Advisor

Mark Rentschler

Third Advisor

Karen, King

Abstract

Over 23 million people in the United States are plagued by diabetes mellitus. Studies have shown that those with diabetes have a higher occurrence of bone fractures than those without the disease, but risk factors associated with diabetes account for only a portion of these fractures (Schwartz 2003; Vestergaard 2006). This implies that there are properties of diabetic bones that account for this increase in fractures. Research has been performed on the bone mineral density (BMD) of those with and without diabetes. However, studying this singular property of bones does not fully explain the increase in bone fractures in the diabetic population. Additionally, this research has yielded inconclusive results: some studies show that diabetes leads to an increase in BMD while others show a decrease in this property (Krakauer et al. 1995; Retzepi & Donos 2010). The objective of this study is to analyze the effect of experimental diabetes on bone properties in mice. This relationship is explored through analyzing different mouse strains to determine a potential genetic link, kidney removal to mimic the effects of nephropathy, and an LXR agonist to explore a potential diabetes treatment. We hypothesize that diabetes will negatively impact bone properties across multiple strains of mice, kidney removal will further degrade bone properties and the LXR agonist will improve some of the negative bone effects that diabetes causes. In general, STZ-induced diabetes was accompanied by decreases in physical and compositional bone properties in both strains of mice. Kidney removal and treatment with an LXR-agonist had little to no effects on these bone properties. Kidney removal was performed in skeletally mature mice; this old age may have contributed to the lack of effects. Similarly, the LXR agonist was administered over a short time period, and the detrimental effects from the diabetes were not able to be overcome. The data presented here provides evidence that experimentally-induced diabetes corresponds with a decrease in bone properties and nephropathy. While LXR agonists hold promise for mitigating bone property changes in diabetes, further analysis is required to determine their potential effects.

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