Metzger, Corinne E.Swallow, Elizabeth A.Stacy, Alexander J.Tippen, Samantha P.Hammond, Max A.Chen, Neal X.Moe, Sharon M.Allen, Matthew R.2020-10-302020-10-302020Metzger, C. E., Swallow, E. A., Stacy, A. J., Tippen, S. P., Hammond, M. A., Chen, N. X., Moe, S. M., & Allen, M. R. (2020). Reversing cortical porosity: Cortical pore infilling in preclinical models of chronic kidney disease. Bone, 115632. https://doi.org/10.1016/j.bone.2020.115632https://hdl.handle.net/1805/24209Purpose 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. Methods 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-H2O; 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-H2O (3%) supplementation. Results Exp 1: Untreated adenine mice had elevated blood urea nitrogen (BUN), parathyroid hormone (PTH), and cortical porosity (~2.6% porosity) while Ca-H2O 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-H2O, 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. Conclusion Ca-H2O 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.enPublisher Policychronic kidney diseasebonecortical porosityArticle