Assessment of Trabecular Bone Architecture and Intrinsic Properties of Cortical bone Tissue in a Mouse Model of Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is often associated with increased fracture risk; however, the CKD-effects on bone microstructure and intrinsic material properties have not been fully elucidated. This study was undertaken to evaluate the time course of trabecular architectural changes and material properties of cortical bone in the tibia of a mouse model of high-turnover CKD. Male mice subjected to 5/6 nephrectomy (Nx, n=8) and those sham-operated (Sham, n=8) were used. Starting at 8 weeks of age (2 weeks after surgery), Nx mice were fed with high phosphate diet. The tibial metaphysis was scanned by in vivo micro-computed tomography (μCT) for trabecular architecture analysis from 10 to 26 weeks of age with 4-week interval. Then, the animal was blood-sampled before sacrifice, and the scanned tibia was harvested. The midlayer of a cortical cross-section was evaluated for mineral-to-matrix ratio, mineral maturity, and collagen maturity by Fourier transform infrared microspectroscopy and for stiffness and hardness by the nanoindentation test. Serum chemicals showed the successful induction of high-turnover CKD in Nx. The age-related regression of trabecular network was observed in both groups but to the higher degree in Nx. In vivo μCT revealed significant interactions between age and CKD in trabecular number, thickness, and separation. On the other hand, the chemical and mechanical properties of cortical bone did not differ significantly between Nx and Sham. Thus, the compromised trabecular architecture will be contributory to bone fragility in high-turnover CKD.