Hypovitaminosis D in pregnancy in the Mediterranean region: a systematic review.

Despite high levels of sunshine, maternal hypovitaminosis D during pregnancy is prevalent in the Mediterranean region. The aim of this study is to systematically review trials that investigated vitamin D concentrations during pregnancy in this region, in order to determine predictors of hypovitaminosis D and explain this phenomenon. After applying inclusion/exclusion criteria, 15 studies were entered into the systematic review involving 2649 pregnant women and 820 neonates. The main outcome was maternal vitamin D status, assessed by serum 25-hydroxy-vitamin D (25(OH)D) concentrations. Possible predictors of the outcome included maternal age, body mass index (BMI), race, socioeconomic status, skin type, gestational age, sun exposure, calcium and vitamin D intake and supplementation, smoking status, parity and season of delivery. Studies differed widely in vitamin D deficiency criteria, method of measurement and outcomes. The prevalence of vitamin D insufficiency ranges from 9.3 to 41.4%, whereas that of vitamin D deficiency from 22.7 to 90.3%. A positive association with 25(OH)D concentrations exists for light skin color, white race, uncovered dressing pattern, maternal vitamin D supplementation and season of gestation (spring/summer). An inverse association exists for BMI and gestational age, whereas data for smoking and socioeconomic status are controversial. We concluded that vitamin D deficiency in pregnancy seems to be quite common, even in the Mediterranean region. Racial, social and cultural habits, as well as the absence of preventive supplementation/dietary strategies, seem to negate the benefits of sun exposure.

Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009-2011 rates.

BACKGROUND: Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20 ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D-1,25(OH)2D takes place at 40 ng/mL in pregnant women. OBJECTIVE: Post-hoc analysis of the relationship between 25(OH)D concentration and preterm birth rates in the NICHD and TRF studies with comparison to Charleston County, South Carolina March of Dimes (CC-MOD) published rates of preterm birth to assess potential risk reduction in the community. METHODS: Using the combined cohort datasets (n=509), preterm birth rates both for the overall population and for the subpopulations achieving 25(OH)D concentrations of ≤20 ng/mL, >20 to <40 ng/mL, and ≥40 ng/mL were calculated; subpopulations broken down by race/ethnicity were also examined. Log-binomial regression was used to test if an association between 25(OH)D serum concentration and preterm birth was present when adjusted for covariates; locally weighted regression (LOESS) was used to explore the relationship between 25(OH)D concentration and gestational age (weeks) at delivery in more detail. These rates were compared with 2009-2011 CC-MOD data to assess potential risk reductions in preterm birth. RESULTS: Women with serum 25(OH)D concentrations ≥40 ng/mL (n=233) had a 57% lower risk of preterm birth compared to those with concentrations ≤20 ng/mL [n=82; RR=0.43, 95% confidence interval (CI)=0.22,0.83]; this lower risk was essentially unchanged after adjusting for covariates (RR=0.41, 95% CI=0.20,0.86). The fitted LOESS curve shows gestation week at birth initially rising steadily with increasing 25(OH)D and then plateauing at ∼40 ng/mL. Broken down by race/ethnicity, there was a 79% lower risk of preterm birth among Hispanic women with 25(OH)D concentrations ≥40 ng/mL (n=92) compared to those with 25(OH)D concentrations ≤20 ng/mL (n=29; RR=0.21, 95% CI=0.06,0.69) and a 45% lower risk among Black women (n=52 and n=50; RR=0.55, 95% CI=0.17,1.76). There were too few white women with low 25(OH)D concentrations for assessment (n=3). Differences by race/ethnicity were not statistically significant with 25(OH)D included as a covariate. Compared to the CC-MOD reference group, women with serum concentrations ≥40 ng/mL in the combined cohort had a 46% lower rate of preterm birth overall (n=233, p=0.004) with a 66% lower rate among Hispanic women (n=92, p=0.01) and a 58% lower rate among black women (n=52, p=0.04). CONCLUSIONS: In this post-hoc analysis, achieving a 25(OH)D serum concentration ≥40 ng/mL significantly decreased the risk of preterm birth compared to ≤20 ng/mL. These findings suggest the importance of raising 25(OH)D levels substantially above 20 ng/mL; reaching 40 ng/mL during pregnancy would reduce the risk of preterm birth and achieve the maximal production of the active hormone.

Impact of vitamin D supplementation on adiposity in African-Americans.

BACKGROUND: African-Americans have higher rates of obesity-associated chronic diseases. Serum 25-hydroxyvitamin D (25(OH)D) shows an inverse association with obesity status. We investigated whether vitamin D supplementation changes body mass index (BMI). SUBJECTS: In total, 328 overweight African-Americans were enrolled over three consecutive winter periods (2007-2010) into a randomized, double-blind, placebo-controlled trial to receive cholecalciferol supplementation (0, 1000 international units (IU), 2000 IU or 4000 IU per day) for 3 months. Plasma concentrations of 25(OH)D and anthropometric measurements were done at baseline, 3 and 6 months. RESULTS: At 3 months, vitamin D supplementation in three dose groups (1000 IU, 2000 IU or 4000 IU per day) did not cause any significant changes in BMI as compared with placebo group 3-month change in BMI per 1000 IU per day estimate (SE): 0.01 (0.039); P=0.78. CONCLUSIONS: In overweight African-Americans, short-term high-dose vitamin D supplementation did not alter BMI.

Post-hoc comparison of vitamin D status at three timepoints during pregnancy demonstrates lower risk of preterm birth with higher vitamin D closer to delivery.

There have been observational reports that maternal vitamin D status at baseline and not closest to delivery is a better predictor of pregnancy outcomes, suggesting that a cascade of events is set into motion that is not modifiable by vitamin D supplementation during later pregnancy. To address this issue, in this exploratory post-hoc analysis using correlation and logistic regression, we sought to measure the strength of the association between serum 25(OH)D concentrations at 3 timepoints during pregnancy: baseline, 1st trimester (<16 weeks); 2nd trimester (16-26 weeks); and 3rd trimester (≥27 weeks) and preterm birth. It was hypothesized that the 25(OH)D value closest to delivery would be most significantly associated with preterm birth. To accomplish this objective, the datasets from NICHD (n=333) and Thrasher Research Fund (n=154) vitamin D supplementation pregnancy studies were combined. The results of this analysis were that 25(OH)D values closer to delivery were more strongly correlated with gestational age at delivery than earlier values: 1st trimester: r=0.11 (p=0.02); 2nd trimester: r=0.08 (p=0.09); and 3rd trimester: r=0.15 (p=0.001). When logistic regression was performed with preterm birth (<37 weeks) as the outcome and 25(OH)D quartiles as the predictor variable, adjusting for study and participant race/ethnicity, as with the correlation analysis, the measurements closer to delivery were more significantly associated and had a higher magnitude of effect. That is, at baseline, those who had serum concentrations <50nmol/L (20ng/mL) had 3.3 times of odds of a preterm birth compared to those with serum concentrations ≥100nmol/L (40ng/mL; p=0.27). At 2nd trimester, the odds were 2.0 fold (p=0.21) and at the end of pregnancy, the odds were 3.8 fold (p=0.01). The major findings from this exploratory analysis were: (1) maternal vitamin D status closest to delivery date was more significantly associated with preterm birth, suggesting that later intervention as a rescue treatment may positively impact the risk of preterm delivery, and (2) a serum concentration of 100nmol/L (40ng/mL) in the 3rd trimester was associated with a 47% reduction in preterm births. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer.

BACKGROUND: In an earlier study, a 25-hydroxyvitamin D(3) (25(OH)D) score calculated from known predictors of vitamin D status significantly predicted plasma levels of 25(OH)D and the risk of colorectal cancer, but the influence of the 25(OH)D score on survival after diagnosis is unknown. MATERIALS AND METHODS: We prospectively examined the influence of post-diagnosis predicted 25(OH)D levels on mortality among 1017 participants in the Nurses' Health Study and Health Professionals Follow-Up Study who were diagnosed with colorectal cancer from 1986 to 2004. Colorectal cancer-specific and overall mortality according to quintiles of predicted 25(OH)D levels were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) adjusted for other risk factors of survival. RESULTS: Higher predicted 25(OH)D levels were associated with a significant reduction in colorectal cancer-specific (P trend=0.02) and overall mortality (P trend=0.002). Compared with levels in the lowest quintile, participants with predicted 25(OH)D levels in the highest quintile had an adjusted HR of 0.50 (95% CI, 0.26-0.95) for cancer-specific mortality and 0.62 (95% CI, 0.42-0.93) for overall mortality. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of colorectal cancer may be associated with improved survival. Further study of the vitamin D pathway in colorectal cancer is warranted.

Diagnosis and treatment of vitamin D deficiency.

The recent discovery--in a randomised, controlled trial--that daily ingestion of 1100 IU of colecalciferol (vitamin D) over a 4-year period dramatically reduced the incidence of non-skin cancers makes it difficult to overstate the potential medical, social and economic implications of treating vitamin D deficiency. Not only are such deficiencies common, probably the rule, vitamin D deficiency stands implicated in a host of diseases other than cancer. The metabolic product of vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone that targets > 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. A common misconception is that government agencies designed present intake recommendations to prevent or treat vitamin D deficiency. They did not. Instead, they are guidelines to prevent particular metabolic bone diseases. Official recommendations were never designed and are not effective in preventing or treating vitamin D deficiency and in no way limit the freedom of the physician--or responsibility--to do so. At this time, assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis and to assure that treatment is adequate and safe. The authors believe that treatment should be sufficient to maintain levels found in humans living naturally in a sun-rich environment, that is, > 40 ng/ml, year around. Three treatment modalities exist: sunlight, artificial ultraviolet B radiation or supplementation. All treatment modalities have their potential risks and benefits. Benefits of all treatment modalities outweigh potential risks and greatly outweigh the risk of no treatment. As a prolonged 'vitamin D winter', centred on the winter solstice, occurs at many temperate latitudes, < or = 5000 IU (125 microg) of vitamin D/day may be required in obese, aged and/or dark-skinned patients to maintain adequate levels during the winter, a dose that makes many physicians uncomfortable.

Neonatal vitamin D status at birth at latitude 32 degrees 72': evidence of deficiency.

OBJECTIVE: With vitamin D deficiency as a serious public health problem, vitamin D status at birth was measured in neonates at latitude 32 degrees 72' (southeastern United States). STUDY DESIGN: In umbilical cord blood, vitamin D status, demonstrated by circulating 25-hydroxyvitamin D, was measured and related to race and season of birth. RESULT: The mean+/-standard deviation of 25-hydroxyvitamin D in 100 cord blood samples was 13.5+/-8.3 ng/ml for the cohort. African-American infants, with a mean+/-standard deviation of 10.5+/-6.0 ng/ml, demonstrated significantly lower vitamin D status than Caucasian infants, with a mean+/-standard deviation of 19.5+/-9.6 ng/ml (P<0.0001). By season, the mean 25-hydroxyvitamin D level at birth in November-March compared to April-October was 11.3 ng/ml lower in Caucasian infants (from 29.0 to 17.7 ng/ml) and 3 ng/ml lower in African-American infants (from 13.1 to 10.1 ng/ml). CONCLUSION: The prevalence of vitamin D insufficiency is high in this cohort. African-American infants demonstrate significantly lower vitamin D status at birth than Caucasian infants. Seasonality, while significant in both groups, had a greater impact on the vitamin D status of Caucasian newborns.

Low vitamin D status despite abundant sun exposure.

CONTEXT: Lack of sun exposure is widely accepted as the primary cause of epidemic low vitamin D status worldwide. However, some individuals with seemingly adequate UV exposure have been reported to have low serum 25-hydroxyvitamin D [25(OH)D] concentration, results that might have been confounded by imprecision of the assays used. OBJECTIVE: The aim was to document the 25(OH)D status of healthy individuals with habitually high sun exposure. SETTING: This study was conducted in a convenience sample of adults in Honolulu, Hawaii (latitude 21 degrees ). PARTICIPANTS: The study population consisted of 93 adults (30 women and 63 men) with a mean (sem) age and body mass index of 24.0 yr (0.7) and 23.6 kg/m(2) (0.4), respectively. Their self-reported sun exposure was 28.9 (1.5) h/wk, yielding a calculated sun exposure index of 11.1 (0.7). MAIN OUTCOME MEASURES: Serum 25(OH)D concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a circulating 25(OH)D concentration less than 30 ng/ml. RESULTS: Mean serum 25(OH)D concentration was 31.6 ng/ml. Using a cutpoint of 30 ng/ml, 51% of this population had low vitamin D status. The highest 25(OH)D concentration was 62 ng/ml. CONCLUSIONS: These data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UV exposure appears to be approximately 60 ng/ml, it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation.

Bioavailability of vitamin D from fortified process cheese and effects on vitamin D status in the elderly.

We conducted 2 studies to determine the effect of vitamin D-fortified cheese on vitamin D status and the bioavailability of vitamin D in cheese. The first study was designed to determine the effect of 2 mo of daily consumption of vitamin D3-fortified (600 IU/d) process cheese on serum 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), and osteocalcin (OC) concentrations among 100 older (> or =60 yr) men and women. Participants were randomized to receive vitamin D-fortified cheese, nonfortified cheese, or no cheese. Serum levels of 25-OHD, PTH, and OC were measured at the beginning and end of the study. There were no differences in 25-OHD, PTH, or OC after 2 mo of fortified cheese intake. The vitamin D-fortified cheese group had a greater decrease in 25-OHD than other groups, due to higher baseline 25-OHD. A second study was conducted to determine whether the bioavailability of vitamin D2 in cheese (delivering 5880 IU of vitamin D2/56.7-g serving) and water (delivering 32,750 IU/250 mL) is similar and whether absorption differs between younger and older adults. The second study was a crossover trial involving 2 groups of 4 participants each (younger and older group) that received single acute feedings of either vitamin D2-fortified cheese or water. Serial blood measurements were taken over 24 h following the acute feeding. Peak serum vitamin D and area under the curve were similar between younger (23 to 50 yr) and older (72 to 84 yr) adults, and vitamin D2 was absorbed more efficiently from cheese than from water. These studies demonstrated that vitamin D in fortified process cheese is bioavailable, and that young and older adults have similar absorption. Among older individuals, consuming 600 IU of vitamin D3 daily from cheese for 2 mo was insufficient to increase serum 25-OHD during limited sunlight exposure.

Soy protein: its effects on intestinal calcium transport, serum vitamin D, and insulin-like growth factor-I in vvariectomized rats.

Recent reports indicate that soy protein and its isoflavones exert beneficial effects on bone in ovarian hormone deficiency. These positive effects, in part, may be due to improved intestinal calcium (Ca) absorption. We examined the role of soy protein or its isoflavones on intestinal Ca transport using ovariectomized rats. Rats were fed either a casein- or a soy protein-based diet with normal or depleted isoflavone levels. After 35 days of treatment, rats were exsanguinated and isolated cells from all intestinal segments were used to measure in vitro Ca transport. Ovariectomy significantly decreased the rates of Ca transport in duodenal and colonic cells, which were prevented by soy protein with normal isoflavone content. This enhanced Ca transport by isoflavones present in soy protein appeared to be independent of circulating insulin-like growth factor-I, 25(OH)vitamin D, or l,25(OH)2vitamin D as these variables were unaffected by dietary treatments. The findings of this study imply that soy isoflavones may promote Ca absorption in a manner analogous to that of estrogen but without exerting uterotrophic effect. Further studies are needed to explore the mechanism(s) by which soy protein or its isoflavones promote intestinal Ca absorption in ovarian hormone deficiency.

Effects of race on diurnal patterns of renal conservation of calcium and bone resorption in premenopausal women.

Previous studies showed differences in bone and mineral metabolism in African-Americans and Caucasians: reductions in serum 25-hydroxyvitamin D [25(OH)D], urinary calcium and skeletal remodeling and moderate secondary hyperparathyroidism. Diurnal studies were carried out in 7 African-American and 7 white normal premenopausal women matched for age, weight and height to further characterize these racial differences in calcium homeostasis. Serum 25(OH)D was significantly lower and serum intact parathyroid hormone (PTH) was significantly higher in the African-American compared with the white women, whereas serum total calcium, Ca2+, phosphorus and 1,25-dihydroxyvitamin D [1,25(OH)2D] were not different in the two groups. Serum intact PTH increased significantly at night in the white women and did not change in the African-American women. Urinary calcium was 47% lower in the African-American than in the white women during the day but was not different at night. Urinary calcium declined at night by 53% in the white women and by 40% in the African-American women. Stepwise multivariate analysis showed that determinants of urinary calcium were mean 24 h serum intact PTH and serum Ca2+ in the two groups together, mean 24 h serum intact PTH, body mass index (BMI) and serum 25(OH)D in the white women, and BMI in the African-American women. Urinary N-telopeptide of type I collagen, a marker of bone resorption, increased by over 60% at night in both groups and was 25% lower in African-American compared with white women, but the difference was not statistically different. Urinary free deoxypyridinoline also increased at night in both groups and was not racially different. Thus, African-American women show higher serum intact PTH and greater conservation of calcium than white women throughout the day. In both groups, maintenance of serum calcium at night is achieved by increased bone resorption and renal conservation of calcium.

Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients.

BACKGROUND: Osteoporosis diminishes the quality of life in adults with cystic fibrosis (CF). Vitamin D deficiency resulting from malabsorption may be a factor in the etiology of low bone mineral density (BMD) in patients with CF. OBJECTIVE: Absorption of oral ergocalciferol (vitamin D2) and the consequent response of 25-hydroxyvitamin D in 10 adults with CF and exocrine pancreatic insufficiency was compared with that of 10 healthy control subjects. DESIGN: In this pharmacokinetic study, CF patients and control subjects were pair-matched on age, sex, and race. Each subject consumed 2500 microg oral vitamin D2 with a meal. The CF group also took pancreatic enzymes that provided > or = 80000 U lipase. Blood samples were obtained at baseline and at 5, 10, 24, 30, and 36 h after vitamin D2 consumption to measure serum vitamin D2 and 25-hydroxyvitamin D concentrations. RESULTS: Vitamin D2 concentrations in all subjects were near zero at baseline. CF patients absorbed less than one-half the amount of oral vitamin D2 that was absorbed by control subjects (P < 0.001). Absorption by the CF patients varied greatly; 2 patients absorbed virtually no vitamin D2. The rise in 25-hydroxyvitamin D in response to vitamin D2 absorption was significantly lower over time in the CF group than in the control group (P = 0.0012). CONCLUSIONS: Vitamin D2 absorption was significantly lower in CF patients than in control subjects. These results may help explain the etiology of vitamin D deficiency in CF patients, which may contribute to their low BMD.

ApaI polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men.

A number of previous investigations showed significant associations between polymorphisms of the vitamin D receptor (VDR) gene and bone mineral density (BMD). BMD is influenced by hormones and the rate of skeletal remodeling. A study was performed to investigate the possible relationship between Apa I, Bsm I, Taq I, and Fok I polymorphisms of the VDR gene and serum 1,25-dihydroxyvitamin D (1,25[OH]2D), osteocalcin, and propeptide of type I collagen (PICP)-markers of bone turnover, total body calcium, and BMD of the total body, radius, lumbar spine, trochanter, and femoral neck-in 39 young adult black men of 20 to 40 years of age and 44 age-, height-, and weight-matched white men. The distribution of each of the four alleles of the VDR genotypes was similar in the two racial groups. The Apa I VDR genotype was associated with serum PICP (P =.0494) but not with serum 1,25(OH)2D or serum osteocalcin. A significant association between the Apa I VDR genotype and BMD of the lumbar spine (P =.0291) was also observed. However, the Bsm I, Taq I, and Fok I genotypes were not significantly associated with BMD or serum osteocalcin, PICP, or 1,25(OH)2D. Multivariate stepwise analysis indicated that (1) the Apa I VDR genotype was associated with BMD of the lumbar spine in the two groups together; with total body calcium and BMD of the total body, radius, trochanter, and femoral neck in the black men; and with BMD of the radius in the white men; analysis also indicated that (2) race was significantly associated with total body calcium and BMD of the total body, lumbar spine, and femoral neck. In summary, the Apa I VDR genotype is associated with serum PICP and BMD at a number of sites but does not contribute to or account for racial differences in BMD in young adult men.

Comparison of commercially available (125)I-based RIA methods for the determination of circulating 25-hydroxyvitamin D.

BACKGROUND: Measurement of circulating 25-hydroxyvitamin D [25(OH)D] is important in the management of metabolic bone disease. The aim of this study was to compare two widely used methods for the quantification of circulating 25(OH)D with attention to their abilities to measure 25-hydroxylated ergocalciferol (vitamin D(2)) [25(OH)D(2)] and cholecalciferol (vitamin D(3)) [25(OH)D(3)]. METHODS: We used two commercially available, Food and Drug Administration-approved, radioiodine ((125)I)-based RIA kits for the detection of 25(OH)D (DiaSorin, Stillwater, MN and IDS Ltd, Tyne and Wear, United Kingdom). These methods were tested for general assay performance, including antibody specificity. Results were compared with those of an HPLC-based direct ultraviolet detection method. RESULTS: Within- and between-run CVs were

Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and adenomatous polyps of the distal colorectum.

1,25-dihydroxyvitamin D [1,25(OH)2D] inhibits proliferation and promotes differentiation of human colon cancer cell lines. Epidemiological findings, although not entirely consistent, suggest an inverse relationship between vitamin D intake and colorectal cancer and adenoma, colorectal cancer precursor lesions. We evaluated the relationship of plasma 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] with distal colorectal adenoma among 326 matched case and control pairs (nested in the prospective Nurses' Health Study), who provided blood in 1989-1990 and who underwent endoscopy in 1989-1996. Plasma vitamin D metabolite concentrations were determined blindly by RIA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple conditional logistic regression models. Mean plasma 1,25(OH)2D and 25(OH)D levels did not significantly differ (P = 0.3 and 0.7, respectively) between cases (31.6 +/- 8.4 pg/ml and 26.4 +/- 10.6 ng/ml, respectively) and controls (32.2 +/- 8.6 pg/ml and 26.8 +/-10.2 ng/ml, respectively). However, women whose plasma 1,25(OH)2D concentration was below 26.0 pg/ml (a level typically considered to be below normal) were at increased risk of distal colorectal adenoma (OR, 1.58; 95% CI, 1.03-2.40). Compared with the lowest 1,25(OH)2D quartile, women in the second (OR, 0.64; 95% CI, 0.41-1.02), third (OR, 0.80; 95% CI, 0.50-1.30), or upper (OR, 0.71; 95% CI, 0.43-1.15) quartiles were at a statistically nonsignificant lower risk of adenoma. The relationship was stronger for large/villous adenoma and among those with consistent vitamin D intake over the 10 years prior to blood draw. Compared with women in the lowest quartile, for plasma 25(OH)D, women in the second (OR, 0.64; 95% CI, 0.41-1.00) and third (OR, 0.58; 95% CI, 0.36-0.95) quartiles were at a statistically significantly lower risk of distal colorectal adenoma, but there was no difference in risk in the top quartile (OR, 1.04; 95% CI, 0.66-1.66). We conclude that women who have low levels of circulating 1,25(OH)2D may be at higher risk of distal colorectal adenomas, but additional study is warranted.

Ipriflavone, a synthetic phytoestrogen, enhances intestinal calcium transport in vitro.

Ipriflavone (IP), a synthetic isoflavone, prevents bone loss associated with ovarian hormone deficiency in women and animal models. This protective effect of IP may be partly due to its ability to enhance calcium absorption. The purpose of this study was to examine the effects of IP and 17beta-estradiol (E(2)) on in vitro intestinal calcium transport in an ovariectomized rat model using E(2) as a positive control. Forty-eight 90-day-old female Sprague-Dawley rats were divided into four groups: one sham-operated (sham) and three ovariectomized groups. The ovx groups were either control (ovx), supplemented with IP (100 mg/kg body weight daily) via gavaging (ovx+IP), or injected with E(2) (10 microg/kg body weight) (ovx+E(2)). Animals were fed diets containing 0.4% calcium, 0.3% phosphorus, and 0.195 nmol vitamin D(3)/g for 35 days from the date of surgery. Animals were exsanguinated, and isolated cells from the duodenum, jejunum, ileum, and colon were used to measure in vitro calcium uptake. Calcium uptake by duodenal cells was significantly greater in the IP and E(2)-treated animals compared with the ovx control group. In addition, calcium uptake by the ileal and colonic cells of the E(2)-treated animals was significantly greater compared with all the other groups. The results confirm our earlier findings implicating a role for estrogen in duodenal calcium uptake. The findings also indicate that IP, although less potent than estrogen, significantly enhances calcium uptake in the duodenum, the active site of calcium absorption.

Aminoaciduria in calcium-deficiency rickets in northern Nigeria.

Generalized aminoaciduria is associated with vitamin D-deficiency rickets in humans, but there is little information regarding aminoaciduria in rickets caused by primary calcium deficiency. In contrast to rickets in other parts of the world, this bone disease in Nigeria is caused primarily by inadequate intake of dietary calcium. We conducted a clinical trial in Jos, Nigeria in 10 children with radiographically and biochemically proven rickets; an equal number of non-rachitic healthy children from the same area served as controls. Serum and 24 h urine samples were obtained at baseline and at 24 h, 1 week, 4 weeks, and 12 weeks after initiation of calcium supplementation (1000 mg/day) and were analysed for their content of amino acids. Serum calcium, phosphorus, intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were also measured at each time point. In the rachitic subjects urinary amino acid concentrations were elevated from 2- to 16-fold at baseline, while serum amino acid levels increased 1.5- to 3.8-fold compared to controls. After 12 weeks of calcium supplementation, serum and urine amino acids decreased. There was no correlation between the degree of aminoaciduria and serum PTH or 1,25-dihydroxyvitamin D concentrations. We conclude that the aminoaciduria in these rachitic children was related to their calcium status and not to their vitamin D or PTH status.

Rickets in Nigerian children: response to calcium supplementation.

In a previous study of rachitic children in Jos, Nigeria we concluded that inadequate dietary intake of calcium was the primary contributing factor to the development of their rickets. The objective of the present study was to determine the effect of calcium supplementation in 10 children with radiographically and biochemically proven rickets from the same geographical area. Rachitic children were provided with calcium supplements of 1000 mg/day for a period of 3 months. Serum and urine samples were obtained at baseline and at 24 hours, 1 week, 4 weeks, and 12 weeks after initiation of supplementation. Serum calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were measured at each time point. Dietary recalls obtained at two separate times were used to estimate usual daily intakes of calcium and phosphorus. Ten non-rachitic age-matched controls from the same geographical area were recruited for comparison. Nine of 10 rachitic subjects had radiographic evidence of healing after 3 months of calcium therapy. Although serum calcium concentrations returned to control levels, other biochemical data indicated that the rickets of these subjects may have been multifactorial in aetiology, pointing to a possible defect in the synthesis of 25-hydroxyvitamin D.