Title
Disturbances in bone largely predict aortic calcification in an alternative rat model developed to study both vascular and bone pathology in chronic kidney disease Disturbances in bone largely predict aortic calcification in an alternative rat model developed to study both vascular and bone pathology in chronic kidney disease
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
New York, N.Y. ,
Subject
Biology
Human medicine
Source (journal)
Journal of bone and mineral research. - New York, N.Y.
Volume/pages
30(2015) :12 , p. 2313-2324
ISSN
0884-0431
ISI
000367692100019
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
As current rat models used to study chronic kidney disease (CKD)-related vascular calcification show consistent but excessive vascular calcification and chaotic, immeasurable bone mineralization due to excessive bone turnover, they are not suited to study the bone-vascular axis in one and the same animal. Since vascular calcification and bone mineralization are closely related to each other, an animal model in which both pathologies can be studied concomitantly is highly needed. CKD-related vascular calcification in rats was induced by a 0.25% adenine/low vitamin K diet. To follow vascular calcification and bone pathology over time, rats were killed at week 4, 8, 10, 11 and 12. Both static and dynamic bone parameters were measured. Vascular calcification was quantified by histomorphometry and measurement of the arterial calcium content. Stable, severe CKD was induced along with hyperphosphatemia, hypocalcemia as well as increased serum PTH and FGF23. Calcification in the aorta and peripheral arteries was present from week 8 of CKD onwards. Four and 8 weeks after CKD, static and dynamic bone parameters were measurable in all animals, thereby presenting typical features of hyperparathyroid bone disease. Multiple regression analysis showed that the eroded perimeter and mineral apposition rate in the bone were strong predictors for aortic calcification. This rat model presents a stable CKD, moderate vascular calcification and quantifiable bone pathology after 8 weeks of CKD and is the first one that lends itself to study these main complications simultaneously in CKD in mechanistic and intervention studies.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/cd74e4/c8149b34.pdf
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