Reversing cortical porosity: Cortical pore infilling in preclinical models of chronic kidney disease.

Chronic kidney disease (CKD) patients have a high incidence of fracture due in part to cortical porosity. The goal of this study was to study cortical pore infilling utilizing two rodent models of progressive CKD. Exp 1: Female C57Bl/6J mice (16-week-old) were given dietary adenine (0.2%) to induce CKD for 10 weeks after which calcium water supplementation (Ca-H 2 O; 1.5% and 3%) was given to suppress PTH for another 4 weeks. Exp 2: Male Cy/+ rats were aged to ~30 weeks with baseline porosity assessed using in vivo μCT. A second in vivo scan followed 5-weeks of Ca-H 2 O (3%) supplementation. Exp 1: Untreated adenine mice had elevated blood urea nitrogen (BUN), parathyroid hormone (PTH), and cortical porosity (~2.6% porosity) while Ca-H 2 O lowered PTH and cortical porosity (0.5–0.8% porosity). Exp 2: Male Cy/+ rats at baseline had variable porosity (0.5%–10%), but after PTH suppression via Ca-H 2 O, cortical porosity in all rats was lower than 0.5%. Individual pore dynamics measured via a custom MATLAB code demonstrated that 85% of pores infilled while 12% contracted in size. Ca-H 2 O supplementation causes net cortical pore infilling over time and imparted mechanical benefits. While calcium supplementation is not a viable clinical treatment for CKD, these data demonstrate pore infilling is possible and further research is required to examine clinically relevant therapeutics that may cause net pore infilling in CKD. • CKD-induced cortical porosity was reduced in rodent models after PTH suppression. • Reducing cortical porosity improves bone mechanics in mice with CKD. • Individual pore tracking over time documents pore infilling in CKD animals. [ABSTRACT FROM AUTHOR]