The role of the serum vitamin D binding protein in the actions of the vitamin D analog eldecalcitol (ED-71) on bone and mineral metabolism

摘要

The vitamin D analog ED-71 (eldecalcitol) has been shown to be superior to calcitriol and its precursor alfacalcidol in maintaining or increasing bone mass in women and animal models with osteoporosis. The mechanism for the greater effectiveness of ED-71 is unknown. In the present study, we tested the hypothesis that the higher activity of ED-71 is due to its higher affinity for the serum vitamin D binding protein (DBP) by comparing the activities of orally administered ED-71, calcitriol and 22-oxacalcitriol (OCT) in wild type (WT) and DBP-ablated (DBPko) mice. In 8-week-old male WT mice, the effects of the analogs on serum and urinary calcium and phosphate were ED-71 > calcitriol > OCT. The results in DBPko mice were identical to those of the WT mice for all parameters tested. In ovariectomized mice, ED-71 was more effective than calcitriol in increasing bone mineral density, but again, there were no differences in the responses of the WT versus DBPko OVX mice. This lack of an effect of DBP ablation on the activities of oral ED-71 occurred despite the finding that peak circulating levels of ED-71 were 100 times lower and disappeared quickly in the DBPko mice while the peak levels at 1 h in WT mice were maintained for at least 24 h. These findings indicate that although DBP has a major influence on circulating levels of vitamin D compounds, it is not responsible for the greater efficacy of ED-71 on bone and mineral metabolism.