Mechanical and Material Property Changes in Bone With Experimental Diabetes: A Murine Model

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URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/s7526c745

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.

Cited Works (14)

Year	Entry
2003	Ferguson VL, Ayers RA, Bateman TA, Simske SJ. Bone development and age-related bone loss in male C57BL/6J mice. Bone. March 2003;32(3):387-398.
2010	Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. July 2010;25(7):1468-1486.
1996	Rüegsegger P, Koller B, Müller R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tiss Int. 1996;58(1):24-29.
2000	Akhter MP, Iwaniec UT, Covey MA, Cullen DM, Kimmel DB, Recker RR. Genetic variations in bone density, histomorphometry, and strength in mice. Calcif Tiss Int. October 2000;67(4):337-344.
1996	Beamer WG, Donahue LR, Rosen CJ, Baylink DJ. Genetic variability in adult bone density among inbred strains of mice. Bone. May 1996;18(5):397-403.
1999	Brodt MD, Ellis CB, Silva MJ. Growing C57Bl/6 mice increase whole bone mechanical properties by increasing geometric and material properties. J Bone Miner Res. December 1999;14(12):2159-2166.
1990	Bonadio J, Saunders TL, Tsai E, Goldstein SA, Morris-Wiman J, Brinkley L, Dolan DF, Altschuler RA, Hawkins JE Jr, Bateman JF, Mascara T, Jaenisch R. Transgenic mouse model of the mild dominant form of osteogenesis imperfecta. Proc Natl Acad Sci USA. September 1990;87(18):7145-7149.
1993	Bonadio J, Jepsen KJ, Mansoura MK, Jaenisch R, Kuhn JL, Goldstein SA. A murine skeletal adaptation that significantly increases cortical bone mechanical properties: implications for human skeletal fragility. J Clin Invest. October 1993;92(4):1697-1705.
2001	Ferguson VL. Age-Related Bone Loss and Treatment With Cytokines in Mice [PhD thesis]. Boulder, CO: University of Colorado; 2001.
1998	Akhter MP, Cullen DM, Pedersen EA, Kimmel DB, Recker RR. Bone response to in vivo mechanical loading in two breeds of mice. Calcif Tiss Int. November 1998;63(5):442-449.
1986	Keller TS, Spengler DM, Carter DR. Geometric, elastic, and structural properties of maturing rat femora. J Orthop Res. 1986;4(1):57-67.
1981	Torzilli PA, Takebe K, Burstein AH, Heiple KG. Structural properties of immature canine bone. J Biomech Eng. November 1981;103(4):232-238.
1989	Feldkamp LA, Goldstein SA, Parfitt MA, Jesion G, Kleerekoper M. The direct examination of three‐dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989;4(1):3-11.
1999	Hildebrand T, Laib A, Müller R, Dequeker J, Rüegsegger P. Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res. July 1999;14(7):1167-1174.