1- but not 24-hydroxylation of vitamin D is required for skeletal mineralization in rats.

To evaluate the importance of 1- and 24-hydroxylation of 25-hydroxyvitamin D3 on skeletal mineralization, male and female rats from vitamin D-deficient mothers were administered from weaning either 100 pmol/day of 25-hydroxyvitamin D3, 50 pmol/day of 1,25-dihydroxyvitamin D3, or 100 pmol/day of 24,24-difluoro-25-hydroxyvitamin D3 as their sole source of vitamin D. A separate group of rats did not receive any vitamin D. 1,25-Dihydroxyvitamin D3 was given by constant infusion at a dose that normalized plasma calcium concentrations and produced normal body weight gains. Skeletal mineralization was studied by determining femur organic and ash weights. Femurs were obtained from male rats 6 wk after weaning, from female rats at conception, at the end of lactation, and 6 wk after lactation, and from weanling pups born to the female rats. No striking differences in femur organic and ash weights were found between 25-hydroxyvitamin D3 groups and either the 1,25-dihydroxyvitamin D3 group or the 24,24-difluoro-25-hydroxyvitamin D3 group, whereas the vitamin D-deficient rats had poorly mineralized femurs. These results indicate that 1,25-dihydroxyvitamin D3 at a lower dose is as fully active as 25-hydroxyvitamin D3 in promoting skeletal mineralization in the rat and that preventing the 24-hydroxylation of 25-hydroxyvitamin D3 by administering 24,24-difluoro-25-hydroxyvitamin D3 does not elicit any obvious skeletal abnormality, especially on mineralization.