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Not AvailaMineral imbalances in the body from chronic kidney disease can impact bone turnover and cause cortical bone loss. Synthetic salmon calcitonin is an FDA-approved treatment for bone fragility observed in diseases such as osteoporosis, and clinical trials have demonstrated a reduction in fractures compared to untreated individuals. This study documents the effects of calcitonin on cortical bone using an in vivo mouse model of chronic kidney disease. Serum BUN and PTH are reported. Calcitonin was found to impact at a dose of 50/IU/kg/day five times a week for five weeks. MicroCT was used to evaluate bone quantity measures, such as cortical porosity, thickness, bone area, and long bone structural geometric parameters. It was found that porosity, thickness, and bone geometry are affected by disease, but not by treatment at the specified regime. Small and wide-angle x-ray scattering (SAXS and WAXS) was used to obtain the nanostructure of the mineral-collagen-water composite, including mineral dimensions, -periodicity and collagen spacing. Data from thermogravimetric analysis (TgA) were used to quantify wt.% of the mineral, collagen, and bound water of each sample. Chronic kidney disease was found to decrease collagen spacing to increase mineral weight fractions, and to reduce loosely bound water. There were no changes from chronic kidney disease on the -Periodicity. Treatment increased the weight percent of collagen, with no effect on other bone quality parameters. 

At the nanoscale bone is composed of aligned mineralized collagen fibrils organized into packets along the surface of trabecular bone creating an anisotropic tissue microstructure. Newer packets at the trabecular surfaces are usually less mineralized than older bone in the interior of the trabeculae, which along with irregular mineral deposition within packets, forms a heterogeneous material across the span of a trabeculae. However, finite element (FE) models of bone typically use homogenous isotropic material properties, because it is challenging to build anisotropy and heterogeneity into a model in a way that is applicable to the complex geometries of trabecular bone. Both the material anisotropy and heterogeneity may influence the stress state of trabecular bone, and it is important to understand the implications of such differences for determining bone biomechanical failure. It was hypothesized that taking into consideration both the tissue anisotropy and heterogeneity of bone’s biomechanical properties would alter the expected failure locations by reducing tensile stress on near surface elements of an FE model of canine trabecular bone. The objective of this study was to test this hypothesis and to develop a method to apply anisotropic and heterogeneous material properties to a model automatically from micro-computed tomography (μCT) data.