Time course of rapid bone loss and cortical porosity formation observed by longitudinal μCT in a rat model of CKD.

Abstract

Rodent studies of bone in chronic kidney disease have primarily relied on end-point examinations of bone microarchitecture. This study used longitudinal in vivo microcomputed tomography (in vivo μCT) to characterize the onset and progression of bone loss, specifically cortical porosity, in the Cy/+ rat of model of CKD. Male CKD rats and normal littermates were studied. In vivo μCT scans of the right distal tibia repeated at 25, 30, and 35 weeks were analyzed for longitudinal changes in cortical and trabecular bone morphometry. In vitro μCT scans of the tibia and femur identified spatial patterns of bone loss across distal, midshaft and proximal sites. CKD animals had reduced BV/TV and cortical BV at all time points but developed cortical porosity and thinning between 30 and 35 weeks. Cortical pore formation was localized near the endosteal surface. The severity of bone loss was variable across bone sites, but the distal tibia was representative of both cortical and trabecular changes. The distal tibia was found to be a sensitive suitable site for longitudinal imaging of both cortical and trabecular bone changes in the CKD rat. CKD trabecular bone loss progressed through ~30 weeks followed by a sudden acceleration in cortical bone catabolism. These changes varied in timing and severity across individuals, and cortical bone loss and porosity progressed rapidly once initiated. The inclusion of longitudinal μCT in future studies will be important for both reducing the number of required animals and to track individual responses to treatment.