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

Autor: Metzger CE; Department of Anatomy, Cell Biology, Physiology, Indiana University School of Medicine, Indianapolis, IN, United States., Swallow EA; Department of Anatomy, Cell Biology, Physiology, Indiana University School of Medicine, Indianapolis, IN, United States., Stacy AJ; Department of Anatomy, Cell Biology, Physiology, Indiana University School of Medicine, Indianapolis, IN, United States., Tippen SP; Department of Anatomy, Cell Biology, Physiology, Indiana University School of Medicine, Indianapolis, IN, United States., Hammond MA; Department of Anatomy, Cell Biology, Physiology, Indiana University School of Medicine, Indianapolis, IN, United States., Chen NX; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States., Moe SM; Department of Anatomy, Cell Biology, Physiology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States; Roudebush Veterans Administration Medical Center, Indianapolis, IN, United States., Allen MR; Department of Anatomy, Cell Biology, Physiology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Biomedical Engineering, Indiana University Purdue University of Indianapolis, Indianapolis, IN, United States; Roudebush Veterans Administration Medical Center, Indianapolis, IN, United States. Electronic address: matallen@iu.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2021 Feb; Vol. 143, pp. 115632. Date of Electronic Publication: 2020 Sep 11.
DOI: 10.1016/j.bone.2020.115632
Abstrakt: Purpose: 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-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.
Results: 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.
Conclusion: 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.
(Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: