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The Vitamin D Analog 1α,25-Dihydroxy-2β-(3-Hydroxypropyloxy) Vitamin D3 (Eldecalcitol) is a Potent Regulator of Calcium and Phosphate Metabolism

  • Alex J. BrownEmail author
  • Cynthia S. Ritter
Original Research

Abstract

The vitamin D analog 1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D3 (ED-71 or eldecalcitol) has been developed for treatment of osteoporosis, but its effects on mineral metabolism have not been investigated in detail. In the present study, we compared the effects of eldecalcitol and calcitriol on calcium (Ca) and phosphate (Pi) handling in rats. Oral administration of eldecalcitol (0, 7.5, 20, or 50 pmol) q.o.d. for 2 weeks dose-dependently increased ionized Ca, intestinal Ca absorption, and urinary Ca excretion, while these doses of calcitriol had no significant effects. The highest dose of eldecalcitol did not alter serum Pi but stimulated both intestinal Pi absorption and urinary Pi excretion; the latter was attributable, in part, to increased serum FGF-23. The effects of high-dose eldecalcitol on Ca and Pi absorption and urinary excretion and FGF-23 persisted for several days following cessation of treatment. The higher potency of eldecalcitol on Ca and Pi handling was also observed in parathyroidectomized rats infused with PTH, excluding a role for differential regulation of PTH. Direct measurement of duodenal Ca absorption by the in situ loop method confirmed the higher potency of eldecalcitol in this segment via induction of TRPV6. These studies indicated that with chronic administration eldecalcitol is more potent than calcitriol at stimulating intestinal absorption of Ca and Pi, as well as FGF-23. The mechanisms responsible for the higher potency of eldecalcitol are speculated to be its higher vitamin D-binding protein (DBP) affinity and resistance to metabolism.

Keywords

Intestinal mineral absorption Mineral and electrolyte metabolism PTH/PTHrP Vitamin D 

Notes

Acknowledgment

This work was supported by a research grant from Chugai Pharmaceutical. The authors thank Jane Boudreaux for assistance with the in vivo studies.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Renal DivisionWashington University School of MedicineSt. LouisUSA

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