Bone Morphology and Mechanical Properties in Murine Models of Chronic Kidney Disease

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URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/zp38wc94s

Abstract

The aim of this thesis is to investigate the changes in the bone tissue of mice that occur as a result of Chronic Kidney Disease (CKD). Due to the disruptions in mineral homeostasis and metabolism that result from loss of renal function, individuals with CKD are at a higher risk of bone fracture. In order to study the relationship between CKD and bone responses two surgical models of CKD are used herein: uninephrectomy (UNx) and 5/6 nephrectomy (5/6Nx). In general, surgically induced CKD was accompanied with a decrease in bone quality as measured by µCT morphological analysis, mechanical testing, and quantitative histomorphometry. In male C57BL/6 mice aged 4 months, trabecular number (Tb.N) decreased and trabecular spacing (Tb.Sp) increased 8 weeks after UNx (p > 0.10), however no statistically significant changes in bone strength or microarchitecture were observed after UNx. Eight weeks after 5/6Nx, a model of moderate to severe CKD, male C57BL/6 and FVB mice showed significant decrease in bone mineral density and cortical thickness, although no changes in mechanical properties were observed. Overall, these changes were shown to be compartment and site-specific and reveal that the effects of CKD on bone tissue are complex and variable. Further investigation of the time course of the diseased state as well as dietary phosphate loads must be considered when researching bone effects of CKD in murine models.

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