Title
Dietary 135-fold cholecalciferol supplementation severely disturbs the endochondral ossification in growing dogs
Author
Tryfonidou, M.A.
Holl, M.S.
Stevenhagen, J.J.
Buurman, C.J.
Deluca, H.F.
Oosterlaken-Dijksterhuis, M.A.
van den Brom, W.E.
van Leeuwen, J.P.T.M.
Hazewinkel, H.A.W.
Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding
Publication year
2003
Abstract
The effects of excessive non-toxic dietary Vitamin D3 supplementation on Ca homeostasis with specific effects on endochondral ossification and skeletal remodeling were investigated in a group of growing Great Dane dogs supplemented with cholecalciferol (Vitamin D3; HVitD) versus a control group (CVitD) (1350 μg versus 11.4 μg Vitamin D3 per kilogram diet) from 6 to 21 weeks of age. There were no differences between groups in plasma concentrations of total Ca, inorganic phosphate, growth hormone, and insulin-like growth factor I and no signs of Vitamin D3 intoxication in HVitD. For the duration of the study in HVitD compared to CVitD, plasma levels of parathyroid hormone (PTH) decreased, calcitonin (CT) increased, 25-hydroxycholecalciferol [25(OH)D3] increased 30- to 75-fold, 24,25-dihydroxycholecalciferol [24,25(OH)2D3] increased 12- to 16-fold, and 1,25-dihydroxycholecalciferol [1,25(OH)2D3] decreased by approximately 40%. The latter was attributed to the two-fold increased metabolic clearance rate in the HVitD versus CVitD accompanied by the absence of the anabolic effect of PTH on the production of 1,25(OH)2D3. Fractional Ca absorption (α) did not differ between groups at 8 and 14 weeks of age, whereas at 20 weeks of age α increased by only 16.4% in HViAtD compared to CVitD. Excessive non-toxic Vitamin D3 supplementation resulted in decreased bone remodeling and focal enlargement of the growth plate with morphology resembling those induced by administration of CT. Hypercalcitoninemia and the imbalanced relationship between 1,25(OH)2D3 and 24,25(OH)2D3 are potent candidates for the disturbed endochondral ossification. © 2003 Elsevier Science Inc. All rights reserved.
Subject
Health Toxicology
Analytical research
1,25-Dihydroxycholecalciferol
24, 25-Dihydroxycholecalciferol
Ca absorption
Endochondral ossification
24,25 dihydroxycolecalciferol
Calcitriol receptor
Growth hormone
Parathyroid hormone
Phosphate
Somatomedin C
Aging
Animal
Blood
Bone development
Diet supplementation
Drug effect
Growth plate
Growth, development and aging
Histology
Physiology
24,25-Dihydroxyvitamin D 3
Aging
Animals
Calcifediol
Calcitonin
Calcitriol
Calcium
Cholecalciferol
Dietary Supplements
Dogs
Female
Growth Hormone
Growth Plate
Insulin-Like Growth Factor I
Intestinal Absorption
Kidney
Male
Metabolic Clearance Rate
Osteogenesis
Parathyroid Hormone
Phosphates
Receptors, Calcitriol
Canis familiaris
To reference this document use:
http://resolver.tudelft.nl/uuid:c67eaca7-a2b3-4139-847a-f54ebec151bf
DOI
https://doi.org/10.1016/s0739-7240(03)00018-3
TNO identifier
237061
ISSN
0739-7240
Source
Domestic Animal Endocrinology, 24 (4), 265-285
Document type
article