25OHD Measurements Research Articles

Up Date from the Factors Related to the Development of Endocrine Diseases: A perspective biological chemistry

The endocrine system contributes to the functioning of the body's metabolism, the increase or decrease in hormones favors the formation of disorders that develop metabolic diseases. Aim. Compile information on factors that intervene in the development of endocrinological diseases, mainly in hormonal action and alterations of certain metabolites. Methodology. A bib¬liographic search was carried out in Google Schoolar and PudMed using keywords, the information was analyzed in pairs. Results. Hormonal action is affected by desynchronization in hormonal production, triggering metabolic diseases. Measurement of calcium, phosphorus, PTH, 25OHD, 1.25OHD, calcitonin and osteocalcin help in the diagnosis. Conclusion. Circadian alterations favor the development of metabolic diseases, the participation of the clinical laboratory with specific tests is important.

Vitamin D status and supplementation, calcium supplementation, and timing of natural menopause

Vitamin D status has been inconsistently associated with ovarian reserve and menopause. We used data from the Sister Study cohort to examine the associations of vitamin D supplement use, total 25-hydroxyvitamin D (25OHD) level, and calcium supplement use with the timing of natural menopause. Vitamin D and calcium supplement use were assessed on a questionnaire at baseline (mean age: 46) and two follow-up time points, and characterized in multiple ways based on type, dose, and duration of use. Serum samples from a random subset of participants were analyzed for total 25OHD (25OHD3 + 25OHD2 + epi-25OHD3) using liquid chromatography-mass spectrometry. Menopause was assessed at each yearly follow-up with the question “Have you had a menstrual period in the past 12 months?”; if the response was “no”, age at last menstrual period was recorded. We censored women at time of hysterectomy or medically induced menopause, death, loss to follow-up or October 2020. We used multivariable Cox proportional hazard models with age as the time scale to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs), adjusting for race/ethnicity, education, body mass index, alcohol use, smoking status, and physical activity. Among the 13,102 eligible premenopausal participants, 8897 experienced natural menopause during follow-up. Concomitant use of a multivitamin and a vitamin D supplement was associated with slightly earlier menopause (HR(CI): 1.10 (0.98, 1.24)). None of the remaining vitamin D or calcium supplement variables (alone or in combination) were meaningfully associated with timing of natural menopause. In a subsample with 25OHD measurements (n = 906), neither total 25OHD nor 25OHD3 was associated with timing of menopause. Our study includes, on average, 6 years of follow-up from an average age of 46 years and did not find associations between vitamin D or calcium supplement use and timing of menopause. Future studies should focus on a life course approach to this question and include 25OHD measures from early mid-life when examining menopause timing.

The effect of vitamin D status on non-alcoholic fatty liver disease: a population-based observational study.

The effect of vitamin D status on steatosis has not been fully elucidated. In this study, we planned to investigate this interaction using a large-scale population-based cohort. Patients diagnosed with simple steatosis (K76.0) and non-alcoholic steatohepatitis (NASH) (K75.8) by using the International Classification of Diseases 10th Revision (ICD-10) coding system, and who had 25-hydroxyvitamin D (25OHD) measurements at the diagnosis, were included in the study. Control group comprised subjects without liver diseases. Age, gender, alanine aminotransferase (ALT) and 25OHD levels, and the date of the measurements were recorded. We compared ALT and 25OHD measurements between the patient and control groups, and between the simple steatosis and NASH subgroups. 25OHD levels were lower and ALT levels were higher in the patient group (p < 0.001, effect size = 0.028, and p < 0.001, effect size = 0.442, respectively). Logistic regression analysis showed that when 25OHD levels decrease by 1 ng/dL, it increases the risk of being in the patient group by 3.7%. Our results suggest that vitamin D status may be related to the development of non-alcoholic fatty liver disease (NAFLD). Although this relationship is weak, it may be important in the pathogenesis of steatosis.

Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements.

Children with cystic fibrosis (CF) are susceptible to fat-soluble vitamin deficiencies unless supplemented, but even large doses of vitamin D may not prevent low 25-hydroxyvitamin D (25OHD) concentrations. The explanation for these vitamin D non-responders has been elusive. We utilized data from whole genome sequencing (WGS) to test the hypothesis that genetic variations predict responsiveness to vitamin D supplementation in a prospective cohort study of children with CF in the first 3 years of life. One hundred and one infants born during 2012-2017 and diagnosed with CF through newborn screening were studied. Serum 25OHD concentrations and vitamin D supplement doses were assessed during early infancy and annually thereafter. WGS was performed, the resultant variant calling files processed, and the summary statistics from a recent genome-wide association study were utilized to construct a polygenic risk score (PRS) for each subject. Overall, the prevalence of vitamin D insufficiency (<30ng/mL) was 21% in the first 3 years of life. Among the 70 subjects who always adhered to vitamin D supplement doses recommended by the US CF Foundation guidelines, 89% were responders (achieved vitamin D sufficiency) by 3 years of age, while 11% were transient or non-responders. Multiple regression analysis revealed that PRS was a significant predictor of 25OHD concentrations (p<0.001) and the likelihood of being an earlier responder in the first 3 years of life (p<0.01). A limited SNP analysis revealed variants in four important genes (GC, LIPC, CYP24A1, and PDE3B) that were shown to be associated with 25OHD concentrations and vitamin D responder status. Other determinants included vitamin D supplement dose, season at 25OHD measurement, and pancreatic functional status. Applying WGS in conjunction with utilizing a PRS approach revealed genetic variations that partially explain the unresponsiveness of some children with CF to vitamin D supplementation. Our findings suggest that a nutrigenomics strategy could help promote personalized treatment in CF.

COVID-19 pandemic and vitamin D: rising trends in status and in daily amounts of vitamin D provided by supplements

ObjectivesSince the onset of the COVID-19 pandemic in 2020, there have been plausible suggestions about the need to augment vitamin D intake by supplementation in order to prevent SARS-CoV2 infection...

Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study.

Preterm infants are at increased risk for vitamin D deficiency (VDD). We aimed to assess the adequacy of standardized vitamin D supplementation protocol in very low birth weight (VLBW) infants. Additionally, vitamin D status of mother/infant couples and the associations between vitamin D status at birth and morbidities of the infants were investigated. In this single-center, prospective cohort study blood samples were collected from 55 mothers just before delivery and from their infants at birth and on the 30th day of life (DOL) for 25 hydroxy vitamin D (25OHD) measurements. Vitamin D was initiated in dose of 160IU/kg by parenteral nutrition on the first DOL and oral vitamin D supplementation (400IU/day) was administered when enteral feedings reached 50% of total intake or on the 15thDOL. The median 25OHD levels of the infants were 16.12 (9.14-20.50) in cord blood and 36.32 (31.10-44.44) in venous blood on the 30th DOL (p<0.01). In 98% of the VLBW infants 25OHD reached sufficient levels on the 30th DOL. None of the mothers had sufficient vitamin D levels (25OHD >30ng/mL). Maternal 25OHD levels were correlated with the25OHD levels of the infants in cord blood (r=0.665, p<0.001). There was a significant difference in mean cord 25OHD levels between winter (13.65±5.69ng/mL) and summer seasons (19.58±11.67ng/mL) (p=0.021). No association was found between neonatal morbidity and vitamin D status. The results clearly show that by utilizing the current supplementation protocol, the majority of VLBW infants with deficient/insufficient serum 25OHD levels reached sufficient levels on the 30th DOL. Furthermore, vitamin D levels in mother/infant couples were found to be highly correlated.

25-OHD response to vitamin D supplementation in children: effect of dose but not GC haplotype.

GC/DBP effects on response to vitamin D supplementation have not been well-studied. Thus we assessed free and total 25-OHD after vitamin D treatment across the six common GC haplotypes. This double-blind, randomized study compared two vitamin D3 doses in healthy, urban-dwelling 6-month to 10-year-old children at-risk for vitamin D deficiency. Randomization was stratified by GC haplotype. Children were randomized to receive 2800 or 7000 International Units of vitamin D3 weekly. 25-OHD and 1,25(OH)2D were sampled at baseline and after 1-6 months of supplementation. One hundred ninety-two of 225 enrolled subjects completed the study. After one month, total 25-OHD increased with both doses and were higher with 7000 IU/week (85.5 ± 22.8 nmol/L) compared to 2800 IU/week (76.8 ± 18.0 nmol/L), despite equivalent baseline levels. No further significant increase occurred at 6 months (89.8 ± 35.5 and 74.3 ± 18.3 nmol/L, respectively). Free 25-OHD similarly changed. 25-OHD differed among GC groups at baseline. Although no significant effects of individual GC haplotypes on incremental changes were evident, a trend toward an effect of combined 'at risk' GC alleles on response was evident (P = 0.06). Total 1,25(OH)2D showed modest increases, moreso with the larger dose. In urban-dwelling children at-risk for vitamin D deficiency, 1 month of vitamin D3 2800 IU/week increased 25-OHD across all GC haplotype groups, and somewhat enhanced with 7000 IU/week with no further significant increases after 6 months of supplementation. Free 25-OHD measures offer no monitoring advantage over total 25-OHD.

Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study.

Increased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity. Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio [OR] = 0.95; 95% CI 0.84, 1.08; p = 0.44), hospitalization (OR = 1.09; 95% CI: 0.89, 1.33; p = 0.41), and severe disease (OR = 0.97; 95% CI: 0.77, 1.22; p = 0.77). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency. In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.

Total, Free and Bioavailble 25 OH D and Bone Disease in Primary Hyperparathyroidism

Background: Low levels of vitamin D 25OHD are frequently described in PHP patients. The aim of this study was to evaluate bone parameters and vitamin D status in PHP patients and controls. Methods: Prior to surgery, 64 PHP patients and 63 healthy matched control subjects regarding age, gender and body mass index were enrolled in this study along 18 months. 25OHD and PTH were measured using Roche® Immunoassays. Bone mineral density (BMD) by dual X-ray absorptiometry (DXA) (Hologic QDR 4500) and TBS (InSight™) were determined in all patients and controls. Distribution of total, bioavailable and free (calculated) 25OH and its correlation with TBS and DXA in both groups was evaluated. DBP (vitamin D binding protein) SNPs genetic analysis was performed by ABI 7500 real time PCR System. None of the patients and controls were taking vitamin D supplements before the study. Results: PHP patients had lower BMD values than controls in all sites (p<0.01). TBS measurements were also reduced in PHP patients compared to controls, as expected (1233 vs 1280, p=0.04). There was no statistical difference in free, total and bioavailable 25OHD measurements between the PHP and the control group, mean±SD: 3.4±1.7 vs 3.1±1.7 pg/mL (p=0.44), 22.6± 6.1 vs 20.6± ng/dL (p=0.13) 1.53±0.66 vs 1.41±0.61 ng/mL (p=0.28), respectively. Likewise, there was no statistical difference in DBP haplotypes 1s/1s, 1f/1f, 1s/1f, 2/2, 1s/2, 1f/2 analysis between groups. There was no correlation with 25OHD and DXA measurements in both groups. However, total 25OHD presented statistical significant correlation with TBS measurements in the PHP group (r=0.28; p=0.02) and total, free and bioavailable 25OHD measurements with TBS in the control group (r=0.42; r=0.42; r=0.43; p<0.01). Conclusion: Vitamin D status correlates with TBS, but not with DXA, highlighting the relation of the vitamin D with the microarchitecture bone parameters in both PHP patients and controls. However, this correlation was more evident among controls than in PHP patients, spotlighting the primary hyperparathyroidism effects in bone.

Prevalence of biochemical osteomalacia in adults undergoing vitamin D testing.

Prolonged severe vitamin D deficiency can cause osteomalacia, but the 25-hydroxyvitamin D (25OHD) concentration below which this occurs is unknown. We investigated the prevalence of biochemical osteomalacia in adults with a measurement of 25OHD. 25OHD results between 1/1/2009 and 15/6/2020 were obtained from the regional laboratory database, together with measurements of serum calcium, parathyroid hormone (PTH) and alkaline phosphatase (ALP) within 6months of the index 25OHD. We defined biochemical osteomalacia as all 3 of: albumin-adjusted serum calcium (aCa)<2.0mmol/L, PTH>7.3pmol/L and ALP>150IU/L. Possible osteomalacia was 2/3 criteria with the other test not done. 25OHD measurements associated with significant renal impairment, elevated hepatic transaminases or hypercalcaemia were excluded. 110,046 25OHD measurements were identified over the 11.5years period. After removal of ineligible measurements, 42,171 25OHD measurements from 32,386 individuals with at least 2 of aCa, PTH and ALP were included in analyses. Median 25OHD was 63nmol/L; 8% were <25nmol/L, and 33% were <50nmol/L. Five index 25OHD measurements met the definition of biochemical osteomalacia, and another 11 were possible osteomalacia. After reviewing available clinical records for these 16 episodes, we classified 9 cases as osteomalacia and 7 as other diagnoses. Thus, the prevalence of biochemical osteomalacia was 0.02% (9/42,171) for 25OHD measurements and 0.23% (8/3432) for 25OHD<25nmol/L. All cases of osteomalacia with 25OHD measurements prior to supplementation had 25OHD≤18nmol/L. The prevalence of biochemical osteomalacia is very low, even in individuals with 25OHD<25nmol/L.

Vitamin D Level Stability in Dystrophinopathy Patients on Vitamin D Supplementation

Expert guidelines recommend annual monitoring of 25-hydroxyvitamin D (25-OHD) and maintaining 25-OHD ≥30 ng/ml in patients with dystrophinopathies. We hypothesized that 25-OHD remains stable and requires less frequent monitoring in patients taking stable maintenance doses of vitamin D. We performed a retrospective cohort study, using the electronic health record to identify 26 patients with dystrophinopathies with a baseline 25-OHD ≥30 ng/mL and at least one additional 25-OHD measurement. These patients had received a stable dose of vitamin D for ≥3 months prior to their baseline 25-OHD measurement and throughout follow-up. The main outcome measured was the mean duration time the subjects spent with a 25-OHD ≥30 ng/mL. Only 19% of patients dropped their 25-OHD to < 30 ng/ml, with a mean time to drop of 33 months and a median nadir 25-OHD of 28 ng/mL. These results suggest that measurement of 25-OHD every 2-2.5 years may be sufficient in patients with a baseline 25-OHD ≥30 ng/mL and who are on a stable maintenance dose of vitamin D. Other patients may require more frequent assessments.

Levels of 25 hydroxy vitamin D of serum and broncho-alveolar lavage in patients with pulmonary tuberculosis

Alteration of vitamin D is a risk factor for tuberculosis (TB). To evaluate the pulmonary and serum levels of 25-hydroxy vitamin D (25OHD) in patients with and without pulmonary TB. Two-stage study: the first part was retrospective cross-sectional and the second prospective. Those > 18 years of age who underwent fiberoptic bronchoscopy for suspected pulmonary TB and in whom the infection was confirmed were included. Patients with another type of infection without TB and non-infectious diseases were taken as controls for the first stage and infectious controls without TB in the prospective phase. The measurement of 25OHD was performed by ELFA (enzyme-linked fluorescence assay). The Kruskal-Wallis test was used to evaluate association, considering a value of p < 0.05 to be significant. The data were processed with the SPSS version 23 program. The total sample was 77 patients (35 in the first stage and 42 in the second). The characteristics between the groups were homogeneous. Serum (second phase) and broncho-alveolar lavage (first and second phase) levels of 25OHD were lower in TB patients compared to controls and were independent of serum calcium level (serum: 22.4 ng/mL vs 33 ng/mL, p = 0.006 and broncho-alveolar lavage: 9.7 ng/mL vs 12.2 ng/mL; p = 0.012). There was a significant difference between the levels of 25OHD in both serum and broncho-alveolar lavage in patients with pulmonary TB in relation to their controls.

Failure of national antenatal vitamin D supplementation programme puts dark skinned infants at highest risk: A newborn bloodspot screening study

To determine the prevalence of vitamin D deficiency on dried blood spots (DBS) obtained at newborn blood spot screening (NBS) and thereby test the efficacy of the UK national antenatal supplementation programme in an increasingly ethnically diverse English population. To evaluate the seasonal and ethnic variation in neonatal plasma 25 hydoxyvitamin D (25OHD) and its determinants. Three thousand random DBS samples received at a single regional newborn screening laboratory (52°N) over two one-week periods, one in winter (February 2019) and one in summer (August 2019), were collected. Data was collected from NBS cards on birth weight, gestational age, maternal age, ethnicity, and post code which was replaced with index of multiple deprivation (IMD). 25OHD concentrations were measured on 6mm sub-punch from DBS using quantitative liquid chromatography tandem mass spectrometry adjusted to equivalent plasma values. 25OHD variation with season was assessed using Mann-Whitney U test and ethnic groups compared using Kruskal-Wallis test. Linear regression was used to assess the determinants of 25OHD concentrations. 25OHD measurements were available in 2999 (1580 males) subjects [1499 winter-born and 1500 summer-born]. The majority were white British (59.1%) and born at term (mean±SD gestational age of 38.8±1.8 weeks) with a mean (±SD) birth weight of 3306 (±565) grams. The overall prevalence of vitamin D deficiency [25OHD<30nmol/L (12μg/L)] was 35.7% (n=1070) and insufficiency [30-50nmol/L (12-20μg/L)] 33.7% (n=1010). The median (IQR) 25OHD concentration was significantly lower in the winter-born compared to summer-born [29.1 (19.8, 40.6) vs 49.2 (34.3, 64.8) nmol/L respectively; p<0.001]. Across both seasons, when compared to white British babies (41.6nmol/L), the median 25OHD concentrations were significantly lower in babies of black (30.3nmol/L; p<0.001), Asian (31.3nmol/L; p<0.001), any other mixed (32.9nmol/L; p<0.001), mixed white and black (33.7nmol/L; p<0.05) and any other white (37.7nmol/L; p<0.05) ethnicity. The proportion of deficiency was also higher in babies of Asian (48%), black (47%) and mixed ethnicity (38-44%) compared to any other white (34%) or white British (30%) ethnicity. Season of birth, ethnicity, gestation and maternal age accounted for almost 24% of the variation in 25OHD concentrations. The current UK antenatal supplementation programme fails to protect newborns from vitamin D deficiency, especially those from minority ethnic groups who are at high risk of vitamin D deficiency. Nearly 70% of all newborns and 85% of winter-borns had 25OHD concentrations below 50nmol/L (20μg/L). Almost 50% of babies of Black or Asian origin were deficient at birth, which explains their high risk of hypocalcaemic complications and rickets if left unsupplemented. Our findings call for an immediate review of the delivery of antenatal and infant vitamin D supplementation programmes and implementation of food fortification in the long term.

Vitamin D Status Across Age Groups in Turkey: Results of 108,742 Samples from a Single Laboratory

Objective:The aim was to determine vitamin D status in the general population in Turkey between 2011 and 2016, and to evaluate the effectiveness of the national vitamin D supplementation programme.Methods:Serum 25-hydroxyvitamin D (25-OHD) measurement data were retrieved from an internationally accredited laboratory, operating nationwide. A total of 108,742 measurements of 25-OHD were analyzed using the cut-off values of 0-11 ng/mL, 12-19 ng/mL, 20-49 ng/mL, 50-70 ng/mL and >70 ng/mL for vitamin D deficiency, insufficiency, sufficiency, possibly harmful and excess respectively.Results:The mean±standard deviation 25-OHD level was 21.6±13.3 ng/mL. Mean 25-OHD concentrations by age groups were: 37.3 ng/mL, 30.1 ng/mL and 23.7 ng/mL for <1, 1-10 and 11-18 year old groups, respectively. Mean 25-OHD levels of children <1 year and 1-3 years of age were significantly higher than those found in other age groups. The prevalence of vitamin D deficiency (<12 ng/mL) was lowest in children at 1-3 years of age (5%). In subjects older than 18 years of age, mean 25-OHD levels were 18.2 ng/mL, 20.1 ng/mL, 21.9 ng/mL and 21.1 ng/mL for age groups 19-30, 31-50, 51-70 and >70 years, respectively.Conclusion:Successful implementation of the national vitamin D supplementation programme, appears to have nearly eliminated vitamin D deficiency for children under 1-years of age. However, the positive impact of the vitamin D supplementation diminishes as children get older suggesting that supplementation may be required in the older children and adults. In addition, improved awareness of the benefits and risks of excess vitamin D should prevent unnecessary and excessive use of vitamin D supplements.

Serum 25-hydroxyvitamin D concentration in childhood and risk of islet autoimmunity and type 1 diabetes: the TRIGR nested case\u2013control ancillary study

Aims/hypothesisOur aim was to study the association between serum 25-hydroxyvitamin D (25OHD) concentration and islet autoimmunity and type 1 diabetes in children with an increased genetic risk of type 1 diabetes.MethodsSerum samples for 25OHD measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children in 15 countries. Case children (n = 244) were defined as having positivity for at least two out of four diabetes-associated autoantibodies measured at any one sample. For each case child, two control children were selected matched for country and date of birth (±1 year) (n = 488). Of the case children, 144 developed type 1 diabetes. Serum 25OHD was measured repeatedly in infancy and childhood and was compared according to age at the first seroconversion (at 6, 12 and 18 months prior to and at seroconversion) and calendar age (0, 6, 12 and 18 months).ResultsIn children with islet autoimmunity, mean serum 25OHD concentration was lower 18 months prior to the age of first seroconversion of the case children compared with the control children (57.7 vs 64.8 nmol/l, p = 0.007). In children with type 1 diabetes (n = 144), mean serum 25OHD concentration was lower 18 months prior to the age of the first seroconversion (58.0 vs 65.0 nmol/l, p = 0.018) and at the calendar age of 12 months (70.1 vs 75.9 nmol/l, p = 0.031) than in their control counterparts. Analyses were adjusted for month of sample collection, human leucocyte antigen genotype, maternal type 1 diabetes and sex.Conclusions/interpretationThe results suggest that early postnatal vitamin D may confer protection against the development of type 1 diabetes.Trial registrationClinicalTrials.gov NCT00179777

Serum 25-hydroxyvitamin D levels predict cancer survival: a prospective cohort with measurements prior to and at the time of cancer diagnosis.

PurposeCirculating 25-hydroxyvitamin D (25-OHD) levels have been inversely associated with cancer death, but the nature of this relationship is unclear. We investigated this association using repeated measurements of serum 25-OHD.Patients and methodsPre-diagnostic serum samples were collected in population health surveys in Norway (1973–2004). Participants who subsequently developed cancer (1984–2004) provided a second serum sample at the time of cancer diagnosis. Samples were stored in the Janus Serum Bank. Repeated samples existed from 202 breast cancers, 193 lung cancers, 124 lymphomas, and 37 colon cancers. Serum 25-OHD was measured via competitive radioimmunoassay. Cox regression models assessed associations between 25-OHD and cancer-specific death (case fatality) through 2012, given as hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsThe median time between pre-diagnostic and diagnostic samples was 14.4 years. The median 25-OHD levels were 63.3 and 62.5 nmol/L, respectively. During follow-up, 313 cancer deaths occurred. Compared to low pre-diagnostic 25-OHD levels (<46 nmol/L), higher levels (≥46 nmol/L) had significantly lower HRs (39–54%) of case fatality. This result was also seen for the diagnostic samples. Donors who had both samples at high (≥62 nmol/L) levels had 59% lower HR of case fatality, compared to those for whom both samples were at low levels (<46 nmol/L). Furthermore, versus a decline in serum 25-OHD (median −22.4 nmol/L) from pre-diagnostic to diagnostic samples, a rise (median 22.3 nmol/L) was associated with lower case fatality (HR 0.57, 95% CI 0.43−0.75).ConclusionOur findings suggest a causal relationship between vitamin D and cancer case fatality.

SAT-514 The Decrease in Serum Parathyroid Hormone on Vitamin D Treatment Is Similar When Comparing Increases in Serum Free or Total 25 Hydroxyvitamin D in White and Black Women

Background: Recent advances in measurement of total serum 25OHD (T25D) led to development of free 25OHD (F25D) assays. The free hormone hypothesis states that only F25D which is about 0.02% of T25D is available for conversion to the active metabolite 1,25(OH)2D, the rest is bound to D binding protein (DBP) and albumin. In a previous paper (J Int Med 2018 Aug 23 online)we did not find a change in BMD or bone markers compared to F25D or T25D. A one month vitamin D study reported F25D was more highly correlated than T25D with serum PTH. If confirmed then F25D measurement would be clinically important. Methods: In two 12 month vitamin D placebo/dosing studies in young, old white and black women, serum T25D, F25D and PTH were measured at baseline and 12 months. The main inclusion criteria was vitamin D insufficiency (Diasorin serum T25D ≤ 20ng/ml). Serum T25D was remeasured by LCMS and F25D was measured by Elisa (Future Diagnostics). Serum PTH was measured by immunoassay (Diasorin). Group means were compared by t-test. Linear regression was used to assess percent change in T25D and F25D on percent change in PTH, accounting for age (young, old), race (Caucasians, African Americans) and interactions. Results: In the older women, there were 109 Caucasians and 79 African Americans with baseline measurements of F25D, T25D and PTH. Mean age (± SD) was 69 (± 7.3) years. In the younger women, there were 81 Caucasians and 31 African Americans, mean age 37 (± 5.6) years. In older women, serum T25D was similar in black compared to white women 18.70(±5.57) and 19.63(±5.19) ng/ml, p=0.24. Serum F25D was lower in older African Americans compared to Caucasians 3.38(±1.21) vs 3.73(±1.39) pg/mL (p=0.075). In younger women T25D was significantly lower in blacks 14.33(±4.13) compared to 22.09 (±5.45)ng/ml in whites, p<0.001. F25D was lower in blacks 3.55(±1.17) versus 4.64(±1.25) pg/ml p<0.001. Baseline mean serum PTH was higher in the older black women 44(±21) compared to whites 38 (±14)pg/ml (p=0.03). In young black women serum PTH was higher 44(±18) than white women 31(±10)(p<0.01). Serum PTH decreased on vitamin D. The decrease in PTH compared to levels of serum F25D was similar in young and old, black and white women. The decrease in PTH was 6% for each 1% increase in F25D. The slope for the regression of PTH on serum T25D was steeper in blacks than whites (p<0.01) but did not differ by age. The percent decrease in PTH was 13% in blacks and 5% in whites for each 1% increase in T25D. Summary: The percent decrease in serum PTH after vitamin D was related to increasing free and total 25D in young and old, black and white women. However, black women showed a significantly larger decrease in PTH with T25D, possibly because of more secondary hyperparathyroidism. Because the parathyroid gland has the megalin and cubilin receptors mechanism for uptake of DBP it may not be unexpected that the correlations between serum PTH and free and total 25(OH)D are so similar.

Vitamin D deficiency in children: a challenging diagnosis!

The concern about the assessment of vitamin D status is growing. Numerous publications warn about the high prevalence of vitamin D deficiency, as well as the potential role of vitamin D in non-bone health outcomes. The status of vitamin D is usually assessed by measuring serum total 25-hydroxyvitamin D (25OHD) concentration. This is the major circulating form of vitamin D and keeps an inverse correlation with serum parathyroid hormone (PTH) concentration. A value of 25OHD of 20 ng/ml is generally assumed as threshold of vitamin D sufficiency in epidemiologic studies because serum PTH tends to increase when the 25OHD concentration stands below this value. In pediatric population, very few studies have analyzed this issue and the negative relationship between serum 25OHD and serum PTH is not clear, which is the suitable circulating concentration of 25OHD and the threshold of deficiency being matters of controversy. The majority of 25OHD circulates in serum tightly bound to a globulin (DBP). According to the free hormone hypothesis, protein-bound hormones are not biologically available and it is the free form that exerts or facilitates the physiologic actions. If this is true, factors that affect DBP may alter the interpretation of total serum 25OHD measurements.

28. No Association Between The Prevalence of Hypovitaminosis D And The Occurrence of Fractures Among Overweight/Obese Adolescents

There are conflicting data regarding the association between fracture incidence and serum vitamin D (25OHD) concentrations among adolescents with respect to body mass index (BMI) and age. The current study explored the potential association between a low 25OHD level and fracture among overweight, obese, and morbidly obese adolescents. A case-control study was conducted. We reviewed 1,129 electronic medical records of outpatients aged 12-19 years, who presented to the adolescent clinic of an urban hospital between October 1, 2014 – October 1, 2017 and for whom 25OHD levels were available. Patients were excluded if they had chronic diseases that could affect bone health and/or if they received medications that affected bone and mineral metabolism. Participants were identified as cases if they sustained a low/medium impact fracture 12 months before or after the 25OHD level was measured. Twenty-seven were identified [mean (SD) 3.56 (2.1) months between the fracture and 25OHD measurement], with 26 having their 25OHD level taken <6 months before or after the fracture. Controls were matched by age, race, BMI percentile and the season at which their 25OHD was measured (n=81). 25OHD status was defined as sufficient (>30 ng/mL), insufficient (20-30 ng/mL), and deficient (<20 ng/mL) in accordance with the Endocrine Society Clinical Practice Guidelines. Additionally, data were collected regarding fracture location and mechanism, season, hospitalization, and modality of treatment. Independent sample t-tests were used to evaluate for a difference in the 25OHD levels between the two groups. An alpha of 0.05 was considered statistically significant In total, 108 participants were included in the study. The case participants included 15 males (55.6%) and 12 females (44.4%). The control group was composed of 48 females (59.3%) and 33 males (40.7%). For all participants, the mean age was 15.7 ± 2.4 years. 12% were overweight, 53.7% were obese, and 34.3% were morbidly obese. Most fractures involved the upper extremity (59.3%) and were sustained by a low impact mechanism. The mean 25OHD level was 18.5 ng/mL for case participants and 16.1 ng/mL for control participants (P=0.1), indicating deficiency in both groups. No correlations were found between 25OHD levels and fractures, overall, or in any of the weight groups While extremely low levels of 25OHD were common among the adolescents studied, the occurrence of a fracture did not imply lower 25OHD levels among overweight, obese and morbidly obese adolescents. These data suggest that this costly laboratory testing is not justified with respect to bone health prior to vitamin D supplementation

Single high-dose oral vitamin D3 treatment in New Zealand children with inflammatory bowel disease.

High-dose oral vitamin D (stoss) is a novel treatment in children with inflammatory bowel disease (IBD). Vitamin D supplementation may have benefits in IBD beyond bone health including reduced disease activity and improvements in inflammatory markers. The aim of this study was to retrospectively assess the efficacy, safety and impact on disease activity of single oral high-dose vitamin D3 therapy in New Zealand (NZ) children with IBD and vitamin D deficiency. In this retrospective chart review, children with IBD and vitamin D deficiency [serum 25-OH vitamin D level (25-OHD) <50 nmol/L] in Christchurch, NZ, who were managed with single high-dose vitamin D3 therapy were identified. Measurements of serum 25-OHD, calcium and standard serum inflammatory markers prior to and up to 6 months following stoss therapy were extracted from patient records. Disease activity was also defined using the Pediatric Crohn's Disease (CD) Activity Index (PCDAI) at time points before and 3 months following stoss. Twenty-eight doses of stoss were given to 23 children, aged 3-16 years. Mean 25-OHD levels increased after stoss therapy from 39 nmol/L (95% CI: 37-42 nmol/L) at baseline to 189 nmol/L (148-231 nmol/L) at 1-2 months (P<0.001). All children with 1 month levels measured achieved 25-OHD >75 nmol/L. One child had a serum calcium of 2.7 (normal range, 2.2 to 2.6 mmol/L) 2 weeks after treatment, which normalized on repeat testing 10 days later. PCDAI scores, mean platelet count, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) all reduced significantly from baseline to 3 months following stoss therapy. Single high-dose oral vitamin D therapy was used successfully and safely to manage vitamin D deficiency in these children with IBD. An improvement in inflammatory markers and disease activity scores also occurred following stoss therapy.