Nanostructural changes in bone quality in a mouse model of chronic kidney disease and treatment with calcitonin

Abstract

Mineral 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, $D$-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 $D$-Periodicity. Treatment increased the weight percent of collagen, with no effect on other bone quality parameters.