Effects of excess 1,25-dihydroxycholecalciferol in young rats

The oral administration for 5 days of excess 1 alpha,25-dihydroxycholecalciferol [1,25(OH)2D3] at doses of 1, 5, and 25 micrograms/kg to rats, beginning at the age of 2 or 10 days, produced dose-dependent reductions in weight development and additional calcification near the skeleton. Alizarin red S stained skeleton revealed calcific deposits near the bones of the head, near the neural arches, between the ribs, along the bones both of the fore limbs and, to a lesser extent, of the hind limbs. Histologically, the deposits appeared to be localized primarily in the sub-epithelial connective tissues. Starting treatment with 1,25(OH)2D3 (25 micrograms/kg for 5 days) at the age of 20 days produced additional calcification in 1 of 8 rats at only 1 location (lower jaw). Additional calcification as described above could no longer be induced by 1,25(OH)2D3 in 30-day-old rats using doses up to 25 micrograms/kg and 10 daily treatments. We conclude that the sensitivity of young rats to 1,25(OH)2D3-induced additional calcification, which differs in localization from that observed in adult rats, decreases with the maturation of the animals.