Vitamin D toxicity: initial site and mode of action

Two groups of weanling pigs, injected with ⁴⁵Ca, were fed diets containing optimal calcium and phosphorus, and vitamin D₃ at 1320 IU/kg feed in the control group, and 825,000 IU/kg feed in the test group. The groups were further subdivided with 2 pigs in each subgroup, with survival times of 1, 2, 3, 4, 7 and 14 days. Pigs fed the high level of vitamin D₃ lost weight and anorexia, weakness, rough hair coat and labored breathing were observed. Hypercalcemia began at 12 hours and progressed rapidly after 2 days. Radioisotope studies interpreted in the light of histopathologic findings indicated that bone was the primary source of increased plasma calcium. Calcium was released at a rapid rate into blood from prelabeled bone which was undergoing necrosis; it was also removed from blood and deposited into bone at a slower rate due to decreased apposition.