Dietary 135-fold cholecalciferol supplementation severely disturbs the endochondral ossification in growing dogs

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.