The Vitamin D Analog 1α,25-Dihydroxy-2β-(3-Hydroxypropyloxy) Vitamin D3 (Eldecalcitol) is a Potent Regulator of Calcium and Phosphate Metabolism
The Vitamin D Analog 1α,25-Dihydroxy-2β-(3-Hydroxypropyloxy) Vitamin D3 (Eldecalcitol) is a Potent Regulator of Calcium and Phosphate Metabolism
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DOI：
10.1007/s00223-011-9528-7
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发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Ritter, Cynthia S.
中科院分区：
文献类型：
--
作者：
Brown, Alex J.;Ritter, Cynthia S.
维生素D类似物1 α，25-二羟基-2 β-（3-羟丙氧基）维生素D-3（艾德-71或艾地骨化醇）已被开发用于治疗骨质疏松症，但其对矿物质代谢的影响尚未详细研究。在本研究中，我们比较了艾地骨化醇和骨化三醇对大鼠钙（Ca）和磷（Pi）处理的影响。口服艾地骨化醇（0、7.5、20或50 pmol）q.o.d.持续2周，剂量依赖性地增加了离子钙、肠钙吸收和尿钙排泄，而这些剂量的骨化三醇没有显著影响。最高剂量的艾地骨化醇不会改变血清Pi，但会刺激肠道Pi吸收和尿Pi排泄;后者部分归因于血清FGF-23的增加。高剂量艾地骨化醇对Ca和Pi吸收和尿排泄以及FGF-23的影响在停止治疗后持续数天。在输注PTH的甲状旁腺切除大鼠中也观察到艾地骨化醇对Ca和Pi处理的更高效力，排除了PTH的差异调节作用。通过原位袢法直接测量十二指肠钙吸收，证实艾地骨化醇通过诱导TRPV 6在该段中具有更高的效力。这些研究表明，在长期给药的情况下，艾地骨化醇在刺激Ca和Pi以及FGF-23的肠吸收方面比骨化三醇更有效。推测艾地骨化醇更高效力的机制是其更高的维生素D结合蛋白（DBP）亲和力和对代谢的抗性。
The vitamin D analog 1 alpha,25-dihydroxy-2 beta-(3-hydroxypropyloxy)vitamin D-3 (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.