Low vitamin D status adversely affects bone health parameters in adolescents.

BACKGROUND: The effects of subclinical vitamin D deficiency on bone mineral density (BMD) and bone turnover in adolescents, especially in boys, are unclear. OBJECTIVE: We aimed to investigate the relations of different stages of vitamin D status and BMD and bone turnover in a representative sample of adolescent boys and girls. DESIGN: BMD was measured by dual-energy X-ray absorptiometry at the nondominant forearm and dominant heel in a random sample of 12- (n = 260) and 15-y-old (n = 239) boys and 12- (n = 266) and 15-y-old (n = 250) girls. Serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and type I collagen cross-linked C-telopeptide were assessed by using enzyme-linked immunoassays. Relations between vitamin D status and bone health indexes were assessed by using regression modeling. RESULTS: Using multivariate regression to adjust for potential physical, lifestyle, and dietary confounding factors, we observed that 12- and 15-y-old girls with high vitamin D status (>/=74.1 nmol/L) had significantly greater forearm (but not heel) BMD (beta = 0.018; SE = 0.008; P < 0.05 for each age group) and lower serum parathyroid hormone concentrations and bone turnover markers than did those with low vitamin D status. These associations were evident in subjects sampled throughout the year and in winter only. There was no significant relation between vitamin D status and BMD in boys. CONCLUSIONS: Maintaining serum 25-hydroxyvitamin D concentrations above approximately 50 nmol/L throughout the year may be a cost-effective means of improving bone health. Increased emphasis on exploring strategies for improving vitamin D status in adolescents is needed.

Vitamin D status and its determinants in adolescents from the Northern Ireland Young Hearts 2000 cohort.

Despite recent concerns about the high prevalence of sub-clinical vitamin D deficiency in adolescents, relatively few studies have investigated the underlying reasons. The objective of the present study was to investigate the prevalence and predictors of vitamin D inadequacy among a large representative sample of adolescents living in Northern Ireland (54-55 degrees N). Serum concentrations of 25-hydroxyvitamin D (25(OH)D) were analysed by enzyme-immunoassay in a subgroup of 1015 of the Northern Ireland Young Hearts 2000 cohort; a cross-sectional study of 12 and 15 year-old boys and girls. Overall mean 25(OH)D concentration throughout the year was 64.3 (range 5-174) nmol/l; 56.7 and 78.1 nmol/l during winter and summer, respectively. Reported intakes of vitamin D were very low (median 1.7 microg/d). Of those adolescents studied, 3 % and 36 % were vitamin D deficient and inadequate respectively, as defined by serum 25(OH)D concentrations < 25 and < 50 nmol/l. Of the subjects, 46 % and 17 % had vitamin D inadequacy during winter and summer respectively. Gender differences were also evident with 38 % and 55 % of boys and girls respectively classified as vitamin D inadequate during winter (P < 0.001). Predictors of vitamin D inadequacy during winter were vitamin D intake and gender. In conclusion, there is a high prevalence of vitamin D inadequacy in white-skinned adolescents in Northern Ireland, particularly during wintertime and most evident in girls. There is a clear need for dietary recommendations for vitamin D in this age group and for creative strategies to increase overall vitamin D status in the population.

The effect of two dietary and a synthetic phytoestrogen on transepithelial calcium transport in human intestinal-like Caco-2 cells.

BACKGROUND: Recently, dietary phytoestrogens (PEs) have been suggested as possible alternatives to estrogen therapy, as a means of preventing bone loss associated with ovarian hormone deficiency. PEs are non-steroidal, plant-derived compounds that exhibit some estrogen-like activity in some tissues, and which appear to prevent postmenopausal bone loss. While PEs act directly on bone cells, their protective effect on bone may be partly due to their ability to enhance Ca absorption. AIM OF THE STUDY: Therefore, the aim of this study was to investigate the effect of two dietary PEs (coumestrol and apigenin) as well as a synthetic PE, ipriflavone, on Ca absorption in human Caco-2 intestinal-like cells. METHODS: Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On d 21, the Caco-2 monolayers (n 10-16 per treatment), grown in estrogen-free or low-estrogen media, were then exposed to 10 nM-1,25 (OH)2 D3, or 50 microM ipriflavone, -coumestrol or -apigenin for 48 hours. After exposure, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. RESULTS: As expected, 1,25 (OH)2 D3 stimulated Ca absorption. Treatment with coumestrol or apigenin had no effect on Ca transport. On the other hand, ipriflavone increased total Ca transport (by about 1.5-fold, P < 0.05) under low-estrogen conditions, but not under estrogen-free conditions. This increase in total Ca transport by ipriflavone was via an increased transcellular Ca transport (by about 2-fold, P < 0.05) relative to control. CONCLUSION: In conclusion, the protective effect of dietary PE on bone mass would appear to be due to their direct effect(s) on bone cells, as opposed to an indirect effect on bone by stimulation of intestinal Ca absorption.

Lack of dose-responsive effect of dietary phyto-oestrogens on transepithelial calcium transport in human intestinal-like Caco-2 cells.

Ca absorption has been shown to be unaffected by high luminal concentrations of two commonly consumed soyabean phyto-oestrogens (PO) (genistein and daidzein) in Caco-2 cells grown under oestrogen-depleted conditions. However, these compounds exhibit dose-dependent biphasic effects in some tissues, such as reproductive tissue and bone. Thus, in light of this biphasic activity, the effect of lower concentrations of genistein and daidzein on Ca absorption requires further investigation. Therefore, the aim of the present study was to investigate the effect of a range of concentrations of genistein and daidzein on Ca absorption in the human Caco-2 intestinal-like cell model. Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On day 21, the Caco-2 monolayers (n 12 per treatment), grown in oestrogen-deplete media, were then exposed to 10 nm-1,25-dihydroxycholecalciferol (1,25 (OH)2D3), or 1, 10 and 50 microm-genistein or -daidzein for 24 h. After exposure, transepithelial and transcellular transport of (45)Ca and fluorescein transport were measured. As expected, 1,25 (OH)2D3 stimulated Ca absorption in Caco-2 cells, by up regulating transcellular transport. Ca absorption was unaffected by either PO at luminal concentrations of 1, 10 or 50 microm, typical of intakes by Western and Asian populations as well as supplemental levels, respectively. The results of this model suggest that the proposed beneficial effects of supplemental levels of these PO compounds on bone mass in postmenopausal women more probably arise from direct effects on bone cells, and not by an indirect effect of these compounds on Ca absorption.

The effect of oestrogen and dietary phyto-oestrogens on transepithelial calcium transport in human intestinal-like Caco-2 cells.

Recently, dietary phyto-oestrogens (PO) have been suggested as possible alternatives to oestrogen therapy (hormone replacement therapy) as a means of preventing bone loss associated with ovarian hormone deficiency. While PO, which exhibit oestrogen-like activity, act directly on bone cells, their protective effect on bone may be partly due to their ability to enhance Ca absorption. Therefore, the aim of the present study was to investigate the effect of 17beta-oestradiol and two commonly consumed soyabean PO (genistein and daidzein) on Ca absorption in the human Caco-2 intestinal-like cell model. Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On day 21, the Caco-2 monolayers (n 8-18 per treatment), grown in oestrogen-replete or -deplete media, were then exposed to 10 nm-17beta-oestradiol, 1 nm-1,25-dihydroxycholecalciferol, or 50 micro m-genistein or -daidzein for 24 h. After exposure, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. As expected, 1,25-dihydroxycholecalciferol stimulated Ca absorption in Caco-2 cells, by up-regulating transcellular transport, whereas 17beta-oestradiol had no effect on Ca absorption. Unexpectedly, both PO decreased Ca absorption (by about 17-19 % compared with control, P<0.05), by reducing transcellular Ca transport in Caco-2 cells grown in oestrogen-replete media. This inhibitory effect disappeared when monolayers were grown in oestrogen-deplete media. In conclusion, PO at high luminal concentrations either had no effect or reduced Ca absorption in Caco-2 cells, dependent on oestrogen status. The effect of lower concentrations of these compounds needs to be investigated.