title: Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway.
abstract: Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)2D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)2D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1alpha-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)2D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)2D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD.
authors.affiliation: Department of Clinical Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Sato
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawada
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Nashiki
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Tsuji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Arai
authors.forename: Kyoko
authors.initials: K
authors.lastname: Morita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Taketani
authors.forename: Eiji
authors.initials: E
authors.lastname: Takeda
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary; D004100:Dihydroxycholecalciferols / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D006801:Humans; D007103:Immobilization / Q000009:adverse effects*; D007408:Intestinal Absorption; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism
chemical_list: D002136:Calcium, Dietary; D004100:Dihydroxycholecalciferols; D002118:Calcium