Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis

Abstract

SummaryIntestinal fractional calcium absorption (FCA) was assessed before and after vitamin D3 treatment. Serum 1,25(OH)2D concentration was significantly increased by plain vitamin D3 and reduced by eldecalcitol. The 1α hydroxyl calcidiol and eldecalcitol treatments increased FCA, which may be induced through direct stimulation of vitamin D receptors in the intestine.IntroductionTo assess the effects of vitamin D3 compounds on intestinal FCA and calcium-regulating hormones in post-menopausal osteoporosis, a randomized open-label prospective study was conducted.MethodsForty eligible patients were allocated randomly into four groups: eldecalcitol (ELD; 0.75 μg/day), 1α hydroxyl calcidiol (ALF; 1 μg/day), plain vitamin D3 (800 IU/day), and control. Before and after the 4-week treatment, intestinal FCA was estimated by using a double isotope method, and serum concentrations of calcium-regulating hormones and a bone turnover marker were measured.ResultsThe baseline FCA value of the participants was 21.5 ± 7.9% (mean ± SD) and was significantly correlated with serum 1,25(OH)2D (calcitriol) concentration. After the treatment, the FCA significantly increased by 59.5% (95% CI, 41.6 to 77.4%) in the ELD group and by 45.9% (27.9 to 63.8%) in the ALF group, whereas no significant change in the plain vitamin D3 group was found. Unlike the baseline FCA, post-treatment FCA exhibited no significant correlation with serum calcitriol concentration. Parathyroid hormone levels were suppressed by ALF and plain vitamin D3 but were sustained in the ELD and control groups. Serum calcitriol tended to be suppressed by ELD, whereas plain vitamin D3 treatment increased both serum 25(OH)D and calcitriol concentrations.ConclusionThese findings suggest that oral administration of vitamin D3 analogues (ALF and ELD) stimulates FCA but plain vitamin D3 does not. Those effects of vitamin D3 compounds on FCA were independent of serum calcitriol concentration, suggesting that ALF and ELD may directly stimulate intestinal vitamin D receptors.

Glutathione depleting drugs, antioxidants and intestinal calcium absorption

“…Ca 2+ absorption can also occur via a passive, paracellular route, where the movement of the cation between epithelial cells is made through tight junction (TJ) proteins, which facilitate or block the Ca 2+ movement[ 7 ]. The active transport of Ca 2+ is mainly regulated by the biologically active form of vitamin D, 1,25(OH) 2 D 3 (calcitriol)[ 8 ], by previous activation of a vitamin D receptor (VDR)[ 9 ]. When VDR was deleted specifically in the intestine (VDR int- ) of mice, the intestinal Ca 2+ absorption was decreased, the bone mineralization is inhibited and bone fractures were increased[ 10 ].…”

The Function of the Vitamin D Receptor and a Possible Role of Enhancer RNA in Epigenomic Regulation of Target Genes: Implications for Bone Metabolism

“…This suggests that the VDR-mediated actions of VD in bone growth and metabolism do not target bone tissue directly, but rather mediate serum calcium concentrations sufficient for bone formation. [ 22 23 ] Indeed, an elegant study on mice with selectively ablated VDR in the intestine has shown that calcium mobilization from bone is enhanced when a hypocalcemic state was induced. [ 24 25 ]…”

“…Osteomalacia is attributed to insufficient calcium intake, similar to VD deficiency,[ 1 ] as postulated from the results obtained with VDR mutant mice. [ 10 21 22 23 24 25 ] VD dietary supplementation is widely recommended to prevent a hypocalcemic state, and in the US, calcium is widely distributed through milk. Due to low levels of calcium in water in Japan and in other countries, calcium intake from the diet tends to be insufficient, particularly for the elderly who lose the ability to absorb calcium.…”

“…[ 5 26 ] Furthermore, supplementation of ELD appears beneficial in any anti-osteoporotic drug treatment in terms of target tissues and skeletal cell types. [ 5 23 ] The other anti-osteoporotic drugs on the market modulate bone metabolism by attenuating bone resorption and/or stimulating bone formation for bone fracture prevention. In contrast, the major target tissue for ELD appears to be the intestine and kidney.…”

“…In contrast, the major target tissue for ELD appears to be the intestine and kidney. [ 23 26 ] This difference in the target tissues/cells for ELD and the other drugs warrants the use of ELD as a co-treatment with other anti-osteoporotic drugs.…”