Article ID Journal Published Year Pages File Type
1992890 The Journal of Steroid Biochemistry and Molecular Biology 2006 6 Pages PDF
Abstract

Deficiency in Vitamin D and its metabolites leads to a failure in bone formation primarily caused by dysfunctional mineralization, suggesting that Vitamin D analogs might stimulate osteoblastic bone formation and mineralization. In this study, we compare the effect of selected Vitamin D analogs and active metabolite, 1α,25-dihydroxyvitamin D3, 19-nor-1α, 25-dihydroxyvitamin D2, and 1α-hydroxyvitamin D2 or 1α,25-dihydroxyvitamin D2 on bone formation and resorption.In a mouse calvariae bone primary organ culture system, all Vitamin D analogs and metabolite tested-stimulated collagen synthesis in a dose-dependent manner and 19-nor-1α, 25-dihydroxyvitamin D2 was the most efficacious among three. 19-nor-1α, 25-dihydroxyvitamin D2 and 1α,25-dihydroxyvitamin D2 showed similar potencies and 1α,25-dihydroxyvitamin D3 was less potent than others. Osteocalcin was also up-regulated in a dose-dependent manner, suggesting that the three Vitamin D analogs have the equal potencies on bone formation. 25-Hydroxyvitamin D-24-hydroxylase expression was induced in a dose-dependent manner and 19-nor-1α, 25-dihydroxyvitamin D2 was less potent than other two compounds.In a mouse calvariae organ culture, all induced a net calcium release from calvariae in a dose-dependent manner, but the potency is in the order of 1α,25-dihydroxyvitamin D2 ≅ 1α,25-dihydroxyvitamin D3 > 19-nor-1α, 25-dihydroxyvitamin D2. In a Vitamin D/calcium-restricted rat model, all caused an elevation in serum calcium in a dose-dependent manner. There is no significant difference between 1α,25-dihydroxyvitamin D3 and 1α-hydroxyvitamin D2 in potencies, but 19-nor-1α, 25-dihydroxyvitamin D2 is at least 10-fold less potent than the other two compounds.Our results suggest that Vitamin D analogs have direct effects on bone resorption and formation, and 19-nor-1α, 25-dihydroxyvitamin D2 may be more effective than 1α,25-dihydroxyvitamin D3 and 1α-hydroxyvitamin D2 on stimulating anabolic bone formation.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Biochemistry
Authors
, , , , , , ,