Eldecalcitol is more effective in promoting osteogenesis than alfacalcidol in Cyp27b1-knockout mice

Yoshihisa HirotaI, Kimie Nakagawa, Keigo Isomoto, Toshiyuki Sakaki, Noboru Kubodera, Maya Kamao, Naomi Osakabe, Yoshitomo Suhara, Toshio Okano

研究成果: Article査読

5 被引用数 (Scopus)


Calcium (Ca) absorption from the intestinal tract is promoted by active Vitamin D (1α,25D3). Vitamin D not only promotes Ca homeostasis, but it also inhibits bone resorption and promotes osteogenesis, thus playing a role in the maintenance of normal bone metabolism. Because 1α,25D3 plays an important role in osteogenesis, Vitamin D formulations, such as alfacalcidol (ALF) and eldecalcitol (ELD), are used for treating osteoporosis. While it is known that, in contrast to ALF, ELD is an active ligand that directly acts on bone, the reason for its superior osteogenesis effects is unknown. Cyp27b1-knockout mice (Cyp27b1-/-mice) are congenitally deficient in 1α,25D3 and exhibit marked hypocalcemia and high parathyroid hormone levels, resulting in osteodystrophy involving bone hypocalcification and growth plate cartilage hypertrophy. However, because the Vitamin D receptor is expressed normally in Cyp27b1-/-mice, they respond normally to 1α,25D3. Accordingly, in Cyp27b1-/-mice, the pharmacological effects of exogenously administered active Vitamin D derivatives can be analyzed without being affected by 1α,25D3. We used Cyp27b1-/-mice to characterize and clarify the superior osteogenic effects of ELD on the bone in comparison with ALF. The results indicated that compared to ALF, ELD strongly induces ECaC2, calbindin-D9k, and CYP24A1 in the duodenum, promoting Ca absorption and decreasing the plasma concentration of 1α,25D3, resulting in improved osteogenesis. Because bone morphological measurements demonstrated that ELD has stronger effects on bone calcification, trabecular formation, and cancellous bone density than ALF, ELD appears to be a more effective therapeutic agent for treating postmenopausal osteoporosis, in which cancellous bone density decreases markedly. By using Cyp27b1 -/-mice, this study was the first to succeed in clarifying the osteogenic effect of ELD without any influence of endogenous 1α,25D3.

ジャーナルPLoS ONE
出版ステータスPublished - 2018 10月

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学一般
  • 農業および生物科学一般
  • 一般


「Eldecalcitol is more effective in promoting osteogenesis than alfacalcidol in Cyp27b1-knockout mice」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。