Low 25OHD Research Articles

Vitamin D Supplementation Is Associated with Inflammation Amelioration and Cognitive Improvement in Decompensated Patients with Cirrhosis

Background/Objectives: Decompensated cirrhosis is characterized by systemic inflammation and innate and adaptive immune dysfunction. Hepatic encephalopathy (HE) is a prevalent and debilitating condition characterized by cognitive disturbances in which ammonia and inflammation play a synergistic pathogenic role. Extraskeletal functions of vitamin D include immunomodulation, and its deficiency has been implicated in immune dysfunction and different forms of cognitive impairment. The aim was to assess changes in cognitive function and inflammation in decompensated patients with cirrhosis receiving vitamin D supplementation. Methods: Patients with cirrhosis discharged from decompensation in two tertiary hospitals in Spain (from September 2017 to January 2020) were assessed before, at 6 and 12 months after vitamin D supplementation. A comprehensive neuropsychological battery and neuroinflammatory markers were examined. In a subgroup of patients, peripheral immune blood cells were analyzed. Results: Thirty-nine patients were recruited. Of those, 27 completed the 6 months evaluation and were analyzed [age 62.4 ± 11.3 years; 22 men; Model for End-Stage Liver Disease (MELD) 11.7 ± 4.0; prior overt HE 33%; median 25-hydroxyvitamin D (25OHD) plasma level 12.7 µgr/L] and 22 achieved 12 months assessment. At baseline, learning and memory (R = 0.382; p = 0.049) and working memory (R = 0.503; p = 0.047) subtests correlated with plasma 25OHD levels. In addition, processing speed (R = −0.42; p = 0.04), attention (R = −0.48; p = 0.04), Tinnetti balance (R = −0.656; p < 0.001) and Tinnetti score (R = −0.659; p < 0.001) were linked to neuroinflammation marker IL-1β. Patients with lower 25OHD had a greater proportion of TH1cells at baseline and a larger amelioration of IL-1β and IL-6 following supplementation. An improvement in working memory was found after 25OHD replacement (46.7 ± 13 to 50 ± 11; p = 0.047). Conclusions: This study supports that vitamin D supplementation modulates low-grade inflammation in decompensated cirrhosis providing cognitive benefits, particularly in working memory.

Vitamin D status and its determinants in pregnant women form the Faroe Islands

Abstract Background In regions like the Faroe Islands, where sunlight may be insufficient for vitamin D synthesis, alternative sources such as diet and supplements become crucial. This study focuses on assessing the vitamin D status of pregnant women in the Faroe Islands during the early second trimester, considering the potential implications for maternal and fetal health. Methods A nationwide cross-sectional study (June 2020-April 2022) with 652 women providing blood samples and a questionnaire on demographics, vitamin D intake, and diet. Binary logistic regression assessed predictors of low 25-hydroxyvitamin D (25OHD) levels (<50nmol/L). Plasma 25OHD concentrations were analysed at the local National Hospital using the Alinity i 25-OH Vitamin D assay, employing chemiluminescence microparticle immunoassay (CMIA) for quantitative determination. Results The mean age was 30.7 (SD, 4.9) years; 86% were locally born; 45% resided in the capital area; 49% were overweight (BMI ≥25.0), with a mean pre-pregnancy BMI of 26.0. Most participants (95%) reported vitamin D intake (median of 10µg/day) and consumed vitamin D-rich foods 5.3 times per week. Low 25OHD concentrations were observed in 26% of participants, associated with residency, vitamin D intake, dietary habits, overweight, and sampling time. Maternal age, education, BMI, smoking, and traditional food showed no significant associations. During winter, vitamin D intake correlated more strongly with plasma 25OHD levels (Spearman’s rho, winter: 0.4, p < 0.001; summer: 0.2, p = 0.002). Conclusions Our study’s findings are essential for the health of Faroese pregnant women. 74% of them had sufficient 25OHD levels, which is encouraging. However, low levels were associated with residence, diet, overweight, and winter. This underscores the need for public health efforts to focus on monitoring vitamin D status, promoting vitamin D-rich foods, especially in winter, and monitoring dietary intake to protect maternal and fetal health. Key messages • No previous data on vitamin D status in Faroese pregnant women. • Seasonal variation is observed.

Parathyroidectomy Reduces Inflammatory Cytokines and Increases Vitamin D Metabolites in Patients With Primary Hyperparathyroidism

ContextPrimary hyperparathyroidism (PHPT) is accompanied by a decreased 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (DBP). High parathyroid hormone (PTH) is associated with elevated interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), yet the effect of parathyroidectomy (PTX) on DBP and cytokines is not clear. ObjectiveTo prospectively evaluate the effect of PTX on inflammatory profiles, total and free 25OHD, and DBP in patients with PHPT. MethodsNewly diagnosed patients with PHPT were recruited for the study (n = 70). Twenty-eight patients returned after PTX, 3 months later. Biochemical markers were measured before and after PTX. A group of age and body mass index-matched healthy subjects were included as controls (n = 70). ResultsBefore PTX, patients had lower serum DBP (37.5 ± 6.0 vs 41.5 ± 6.1 mg/dL, P < .001) and total 25OHD (30.1 ± 9.5 vs 33.3 ± 7.9 ng/mL, P < .05) but similar free 25OHD when compared to controls. Serum IL-6, C-reactive protein, and MCP-1 were higher in patients with PHPT (P < .05), whereas interleukin-10 was similar to that in controls. PTX increased total and free 25OHD and DBP (P < .001) and decreased serum IL-6 and MCP-1 (P < .05), but not C-reactive protein and interleukin-10. Multiple regression analysis indicated that the preoperative PTH explained a significant portion of the variance of IL-6 and MCP-1 (P < .05). ConclusionThese findings suggest that PTH may upregulate the production of MCP-1 and IL-6 and downregulate circulating DBP in patients with PHPT that are normalized by PTX. The exact mechanism of IL-6 and MCP-1 on DBP, vitamin D metabolites, and clinical outcomes in patients with PHPT is an area requiring further study.

Vitamin D and its associations with blood pressure in the Chronic Kidney Disease in Children (CKiD) cohort.

Vitamin D (25OHD) can modulate pathways and mechanisms that regulate blood pressure (BP). Observational studies in children and adults have shown an inverse association between 25OHD and BP. Studies evaluating associations between 25OHD and BP in pediatric chronic kidney disease are limited. We evaluated the associations between 25OHD and BP using data from the Chronic Kidney Disease in Children (CKiD) study. Clinic or ambulatory BP index was defined as participant's BP divided by 95th age-sex-height-specific BP percentile, an index > 1 suggests hypertension. Primary outcomes of interest were changes in systolic and diastolic clinic and ambulatory BP indices over follow-up. Linear mixed-effects models were used to evaluate associations between BP indices and 25OHD. The study cohort consisted of 370 participants who contributed 970 person-visits. A subset of 194 participants with ambulatory BP data contributed 465 person-visits. There was an association between baseline 25OHD levels and clinic systolic BP index such that for every 10ng/ml lower 25OHD, clinic systolic BP index was 1.0% higher (95%CI: 0.2-1.8, p = 0.016) between participants. The association between clinic diastolic BP index with baseline 25OHD was not significant. For within-person changes, longitudinal decreases in 25OHD were not significantly associated with concomitant increases in clinic systolic or diastolic BP index. There were no significant associations between 25OHD levels at baseline or longitudinally with 24-h ABPM indices. Low 25OHD levels were associated with higher clinic systolic BP in children with CKD. Vitamin D supplementation to maintain normal 25OHD levels might be a useful adjunctive treatment in optimizing BP control in these high-risk patients.

Ethnic and seasonal variations in FGF-23 and markers of chronic kidney disease-mineral and bone disorder.

Fibroblast growth factor 23 (FGF-23) and other markers of chronic kidney disease-mineral and bone disorder (CKD-MBD) provide valuable insights into disease processes, treatment options and patient prognosis. However, limited research has explored potential associations with ethnicity or season, particularly in multi-ethnic populations residing in high-latitude regions. We evaluated CKD-BMD markers in a diverse cohort of CKD patients, who were participants of The CANADIAN AIM to PREVENT (the CAN AIM to PREVENT) study. FGF-23, calcium, phosphate, 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH) in 1234 participants with pre-dialysis CKD (mean estimated glomerular filtration rate: 41.8±14.3mL/min) were analyzed. Mixed-effects general linear regression models adjusted for demographic and biological factors were used to compare repeated measurements across patient groups categorized by ethnicity (East Asian, White, South Asian, Black, Southeast Asian) and seasons. Compared with other groups, White participants exhibited 8.0%-18.5% higher FGF-23 levels, Black participants had 0.17-0.32mg/dL higher calcium levels, White participants had 10.0%-20.1% higher 25-OHD levels, South Asian participants had 7.3%-20.1% lower 25-OHD levels and Black participants had 22.1-73.8% higher iPTH levels, while East Asian participants had 10.7%-73.8% lower iPTH levels. Seasonal variations were also observed. FGF-23 levels were 11.9%-15.5% higher in summer compared with other seasons, while calcium levels were 0.03-0.06mg/dL lower in summer. 25-OHD levels were 5.6%-10.6% higher in summer and autumn compared with other seasons. This study shows that FGF-23 and CKD-MBD markers in a Canadian pre-dialysis CKD cohort vary independently by ethnicity and season. Further research is needed to understand the reasons and clinical significance of these findings.

Vitamin D and Risk of Incident Type 2 Diabetes in Older Adults: An Updated Systematic Review and Meta-Analysis.

Vitamin D deficiency is very common worldwide, particularly in old age, when people are at the highest risk of the negative adverse consequences of hypovitaminosis D. Additionally to the recognized functions in the regulation of calcium absorption, bone remodeling, and bone growth, vitamin D plays a key role as a hormone, which is supported by various enzymatic, physiological, metabolic, and pathophysiological processes related to various human organs and systems. Accruing evidence supports that vitamin D plays a key role in pancreatic islet dysfunction and insulin resistance in type 2 diabetes. From an epidemiological viewpoint, numerous studies suggest that the growing incidence of type 2 diabetes in humans may be linked to the global trend of prevalent vitamin D insufficiency. In the past, this association has raised discussions due to the equivocal results, which lately have been more convincing of the true role of vitamin D supplementation in the prevention of incident type 2 diabetes. Most meta-analyses evaluating this role have been conducted in adults or young older persons (50-60 years old), with only one focusing on older populations, even if this is the population at greater risk of both hypovitaminosis D and type 2 diabetes. Therefore, we conducted an update of the previous systematic review and meta-analysis examining whether hypovitaminosis D (low serum 25OHD levels) can predict incident diabetes in prospective longitudinal studies among older adults. We found that low 25OHD was associated with incident diabetes in older adults even after adjusting for several relevant potential confounders, confirming and updating the results of the only previous meta-analysis conducted in 2017.

Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases.

Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease. This cross-sectional study included 165 children (91 males, median age 6.9yr range 0.2-17.7yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen. Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes -45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure. In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study.

Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage? In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages. Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear. The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n = 417580), vitamin D deficiency (426 cases and 354812 controls), miscarriage (16906 cases and 149622 controls), and the number of miscarriages (n = 78700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis. This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran's Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively. There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, P = 0.927), or the number of miscarriages (β = -0.004, 95% CI: -0.040 to 0.032, P = 0.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, P = 0.624), or the number of miscarriages (β = 0.001, 95% CI: -0.009 to 0.011, P = 0.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found. This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups. These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to the management of miscarriage. This project was supported by the Hubei Provincial Natural Science Foundation Program General Surface Project (2022CFB200), the Key Research & Developmental Program of of Hubei Province (2022BCA042), the Fundamental Research Funds for the Central Universities (2042022gf0007, 2042022kf1210), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001, JCRCYG-2022-009). All authors have no conflicts of interest to declare. N/A.

Correlation and mediation analysis between plasmapheresis donation behavior and bone mineral density and bone metabolism biomarkers: a cross-sectional study based on plasmapheresis donors at high risk of osteoporosis in China.

As a group of more than 3.67 million people, the bone health of Chinese plasmapheresis donors, which the main population is also a risk group of osteoporosis (OP), has raised concerns. Therefore, this article investigates the relationship between bone mineral density (BMD), bone metabolism indicators, and plasmapheresis donation behavior among some high-risk plasmapheresis donors for OP in China, and further explores the mediating factors through reasonable statistical methods. Recruiting long-term and highly active plasmapheresis donors and new donors to measure the total calcium, albumin (ALB), 25-hydroxy vitamin D (25OHD), parathyroid hormone (PTH), type I procollagen amino-terminal peptide (P1NP), and type I collagen carboxy-terminal peptide (β-CTX) and serum ferritin (SF). Then, multiple linear regression was used to adjust confounding factors. Using restrictive cubic splines to explore the nonlinear relationship. Using the Bootstrap method, investigate whether SF has a mediating effect between plasmapheresis donation behavior and bone metabolism biomakers. Finally, analyze the differences in BMD between the two. Compared to new donors, repeat donors have a lower 25OHD, β-CTX and SF levels, while P1NP and PTH levels are high, with statistical differences. The Bootstrap analysis results show that SF level is a partial mediating factor between plasmapheresis donation behavior and bone metabolism biomakers, with a mediating effect ratio of 21.8%. There was no significant difference in the BMD between the two. Long-term and frequently plasmapheresis donation does not affect the bone mass of even elderly donors at high risk for osteoporosis under the existing collection standards and anticoagulant use in China. However, as a self-regulation way, it does increase the osteogenic activity of the body.

Vitamin D Deficiency in Patients Hospitalized for Heart Failure Living in the Tropics.

Vitamin D, as a steroid hormone, has multiple effects on human body and its deficiency has been associated with an increased risk of heart failure (HF) and unfavorable outcomes. The present study investigated the prevalence of vitamin D deficiency (VDD) and its relationship with cardiometabolic parameters in patients hospitalized for HF living in the city of Recife (latitude 8° South). Analytical cross-sectional study, with men and women aged 40-64 years. The HF group was recruited during hospitalization due to decompensation. A matched control group was recruited from the general endocrine clinics. Vitamin D status was assessed by measuring serum 25-hydroxyvitamin D (25OHD), considering deficiency when 25OHD <20 ng/mL (<50 nmol/L). A total of 243 patients were evaluated (HF group: 161, control group: 82). Lower serum 25OHD levels were observed in the HF group (25.2±9.4 vs. 30.0±7.7ng/mL; p<0.001), as well as a higher prevalence of VDD (27.3% vs. 9.8%; prevalence ratio, 2.80; 95% confidence interval, 1.38-5.67; p=0.002). In patients with HF, VDD was associated with diabetes mellitus (65.9% vs. 41.0%; p=0.005) and female sex (65.9% vs. 44.4%; p=0.015). In the subgroup with VDD, higher values of hemoglobin A1c (7.9% [6.0-8.9] vs. 6.2% [5.7-7.9]; p=0.006) and dyslipidemia were also observed. We found higher rates of VDD in patients hospitalized for HF and this was associated with deleterious laboratory metabolic parameters.

Confirming the association between low serum 25OHD levels in girls with central precocious puberty and its severity

BackgroundTo assess the differences in vitamin D levels in girls with rapidly progressive (RP) or slowly progressive (SP) central precocious puberty (CPP) and to compare whether the factors related to RP-CPP influenced the vitamin D status. A cross-sectional study was performed among girls with CPP classified as RP-CPP or SP-CPP.MethodsThe baseline data, gonadotropin-releasing hormone (GnRH) stimulation test results, serum 25-hydroxyvitamin D (25OHD) levels, and season of sample collection were analyzed.ResultsThe mean 25OHD level in 340 girls was 15.89 ± 6.87 ng/mL, of whom only 10 (2.9%) had normal levels (≥ 30 ng/mL). A total of 114 girls in the SP-CPP group and 226 in the RP-CPP group had similar chronological age, disease course, height SDS, bone mineral density, baseline follicle-stimulating hormone (FSH), peak FSH, and 25OHD levels. Developmental age, body mass index (BMI), BMI SDS, peak luteinizing hormone (LH)/FSH, insulin-like growth factor 1 (IGF-1), and IGF-1 SDS were independent risk factors for RP-CPP. Significant differences were observed among the different serum 25OHD levels in terms of season, disease course, IGF1 level, and BMI SDS (P < 0.05). Moreover, the sampling season was strongly correlated with serum 25OHD levels (r = 0.402, P < 0.001).ConclusionThe vitamin D levels were generally deficient or insufficient in girls with CPP, but were not related to the different types of CPP. High BMI levels, IGF1 levels, or peak LH/FSH ratio, but not vitamin D levels, could promote the progression of RP-CPP. Seasonal factors mainly influenced the vitamin D levels.

Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene.

Vitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele. A cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups. Participants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035). Individuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

Serum 25-hydroxyvitamin D level is associated with short-term glycemic variability metrics derived from continuous glucose monitoring in T2DM

This study aims to investigate the association between 25-hydroxyvitamin D (25OHD) and continuous glucose monitoring-assessed short-term glycemic variability (GV) and HbA1c among patients with type 2 diabetes mellitus (T2DM). We conducted a cross-sectional study recruiting 325 patients. The association between 25OHD and GV metrics (mean amplitude of glycemic excursions [MAGE], coefficient of variation [CV], standard deviation of sensor glucose [SD], and TIR) and HbA1c were analyzed using multivariable linear and logistic regression analyses. The 25OHD level and GV metrics showed significant differences among HbA1c groups (P < 0.01). CV, MAGE, SD and HbA1c decreased, and TIR increased with ascending 25OHD tertiles (P < 0.05). Serum 25OHD was inversely associated with CV (β = − 0.211 [− 0.350 to − 0.071], P < 0.01) and HbA1c (β = − 0.061 [− 0.114 to − 0.031], P < 0.01), and further multivariable analyses confirmed these results (P < 0.05). However, no association of HbA1c and 25OHD was found with the highest tertile of CV. These findings revealed that increased GV and HbA1c were both associated with lower 25OHD, and the relationship between HbA1c and 25OHD was attenuated with higher glucose CV in T2DM. Taken together, the analyses suggest that increasing vitamin D status has effects on improvements in long-term glycemic control and low glycemic variability.

Obstructive sleep apnea and vitamin D: an updated systematic review and meta-analysis.

We pooled data from 18 observational studies involving 5592 individuals. Baseline parameters that might have contributed to the significant differences observed were also analyzed. Patients with OSA had significantly lower serum 25-OHD levels (pooled d + - 0.74 [95% CI: - 1.19 to - 0.28], p < 0.01) and higher prevalence of vitamin D deficiency (pooled log (odds ratio) 0.98 [95% CI: 0.30 to 1.67], p < 0.01) compared to those without OSA. Subgroup analysis demonstrated that these differences were significant only in moderate OSA and severe OSA. Neither age nor BMI nor geographical latitude contributed significantly to the differences observed in serum 25-OHD levels. The use of CPAP did not lead to significant changes in serum 25-OHD levels. Patients with OSA have lower serum 25-OHD levels with a higher prevalence of vitamin D deficiency, regardless of age or BMI, pointing to an independent association between vitamin D and OSA.

Vitamin D Deficiency and Cardiovascular Mortality: Retrospective Analysis "Siena Osteoporosis" Cohort.

Vitamin D is a fat-soluble vitamin that plays a key role in bone metabolism, particularly concerning the regulation of calcium and phosphate homeostasis. Cardiovascular disease (CVD) is the main cause of morbidity and mortality in Western countries. Knowledge of the role of vitamin D in CVD arose from evidence of the vitamin D receptor (VDR) inside the cardiovascular system. In this retrospective analysis, we investigated the relationships between vitamin D status and hospitalization for heart failure (HF), overall mortality and cardiovascular mortality. Between 2004 and 2009, age-stratified, random sampling of elderly men and postmenopausal women in the primary care registers of Siena residents was performed. In total, 174 males (mean ± SD, 65.9 ± 6 years) and 975 females (62.5 ± 6 years) were enrolled in the study. We investigated the association between 25OHD status and hospitalization for HF or causes of mortality. A total of 51 subjects (12 males and 39 females) had been hospitalized for acute HF. At the end of the survey, 931 individuals were alive, while 187 had died (43 males and 144 females). A greater proportion of deceased patients showed low 25OHD (particularly patients with levels below 20 ng/mL). A similar trend was observed concerning the prevalence of patients with 25OHD levels below 20 ng/mL who died from stroke (RR = 2.15; 95% CIs 0.98-4.69; p = 0.06). Low 25OHD levels may be predictive of cardiovascular mortality. Whether vitamin deficiency represents a primitive cause or is a simple bystander in increased cardiovascular mortality should be further investigated in prospective large cohort studies specifically designed to assess CVD risk, including a detailed assessment of cardiac dysfunction and the characterization of atherosclerotic lesions.

Kolekalsiferol sonrası endotel disfonksiyonu ve damar sertliğinin diyaliz modalitesine göre değerlendirilmesi

ABSTRACT&#x0D; Objective: The risk of developing cardiovascular disease (CVD) increases significantly in children with chronic kidney disease (CKD) especially with low serum 25- hydroxyvitamin D (25OHD) levels. Herein; we aimed to compare the effects of vitamin D deficiency and the impact of cholecalciferol treatment on endothelial functions and vascular stiffness in children with CKD receiving hemodialysis (HD), peritoneal dialysis (PD) and non- dialysis(ND).&#x0D; Methods: 7 HD, 7 PD and 27 ND patient groups consisting of 41 children totally with low 25OHD levels were compared among each other in regards of biochemical parameters, flow-mediated dilatation(FMD) and local arterial stiffness before and after a single dose of 300.000 units of cholecalciferol treatment.&#x0D; Results: There was no difference in FMD and local arterial stiffness values between HD, PD and ND patient groups before vitamin D supplementation. Significant increase in endothelium-dependent FMD was observed in all patient groups after intervention with cholecalciferol; however the improvement in endothelium-independent FMD and local arterial stiffness measurements was demonstrated in patients with PD and ND. Baseline parathormon level was higher in patients on dialysis; at the end of the study, significant decrease was detected only in patient group not receiving diaysis.&#x0D; Conclusions: Endothelial dysfunction and impaired vascular stiffness were determined in children with CKD with low 25OHD levels regardless of the disease severity.. Recovery with cholecalciferol therapy revealed that vitamin D deficiency should be corrected even in early stages of CKD to prevent the development of CVD

Thoroughbred Racehorses in Hong Kong Require Vitamin D Supplementation to Mitigate the Risk of Low Vitamin D Status.

There is a paucity of data relating to the vitamin D status of racehorses. We hypothesised that the management of racehorses in Hong Kong (HK) predisposes to low vitamin D status unless they receive dietary supplementation. Serum concentrations of 25-hydroxyvitamin D2 (25OHD2), 25-hydroxyvitamin D3 (25OHD3) and total 25-hydroxyvitamin D (total 25OHD) for 79 non-grazing HK racehorses were compared with those for 22 racehorses training in the United Kingdom (UK) that grazed for ≥1 h/d, and for which published data exists. A nested group of 41 HK horses was sampled twice to determine the effect of the duration in HK on vitamin D status. The HK horses had significantly lower serum concentrations of total 25OHD and 25OHD2 than the UK horses; 25OHD2 was undetectable in 15/79 HK sera and serum concentrations of 25OHD2 declined with the duration in HK. The main determinants of vitamin D status were assessed using linear regression; the retained variables were the 25OHD3 concentration and the duration in HK. The inverse relationship between the serum concentrations of 25OHD2 and 25OHD3, previously identified in humans, was observed for the first time in horses. In conclusion, HK racehorses have low serum 25OHD2 and total 25OHD concentrations and rely on D3 supplementation to maintain adequate vitamin D status. Further study is required to determine the optimal form of dietary vitamin D supplementation for Thoroughbred racehorses.

Pediatric Fractures: Does Vitamin D Play a Role?

Vitamin D (25-OHD) deficiency and insufficiency are reported in about half of all children. The literature on low 25-OHD and pediatric fracture risk presents inconsistent results. This study evaluates the association between pediatric fractures and 25-OHD, parathyroid hormone (PTH), and calcium. This is a prospective case-control study in 2 urban pediatric emergency departments (2014-2017). Patients aged 1 to 17 requiring intravenous access were enrolled. Demographics, nutrition, and activity information were recorded and levels of 25-OHD, calcium, and PTH were measured. Two hundred forty-five subjects were enrolled: 123 fractures and 122 controls. Overall, the mean 25-OHD level was 23ng/mL±8.5: 52 (21%) of patients were 25-OHD sufficient; 193 (79%) were not. Ninety-six percent of patients with lower extremity fractures had low 25-OHD versus 77% of patients with upper extremity fractures (P=0.024). The fracture cohort was younger (P=0.002), included more males (P=0.020), and spent more time playing outdoor sports (P=0.011) than the control cohort. The 25-OHD level (fracture 22.8ng/mL±7.6 vs. nonfracture 23.5ng/mL±9.3, P=0.494) and median calcium level (fracture 9.8mg/dL vs. nonfracture 10.0mg/dL, P=0.054) were similar between cohorts. The median PTH level was higher in the fracture than the control cohort (33 vs. 24.5pg/mL; P<0.0005); PTH was elevated to hyperparathyroidism (>65pg/mL) in 13% of fractures and 2% of controls (P=0.006). Matched subgroup analysis of 81 fracture patients and 81 controls by age, gender, and race showed that PTH was the only variable independently associated with increased odds of fracture (odds ratio=1.10, 95% CI, 1.01-1.19, P=0.021) in a model adjusted for vitamin D sufficiency and time spent playing outdoor sports. Low 25-OHD is common in children with fractures but we found no difference in 25-OHD levels between fracture and nonfracture cohorts. This research can impact evidence-based guidelines on vitamin D level screening and/or supplementation after fracture. Diagnostic level IV-case-control study.

Vitamin D testing in children and adolescents in Victoria, Australia: are testing practices in line with global recommendations?

ObjectiveTo describe changing primary care ordering of serum 25-hydroxyvitamin D (25OHD) tests in Australian children.DesignLongitudinal, population-based descriptive study of 25OHD testing using a large administrative dataset of pathology orders and...

Abstract #1404780: Implementing a Screening Protocol for Endocrinopathies in Patients with Secondary Hemochromatosis due to Sickle Cell Anemia

Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by hemolytic anemia, intermittent small vessel occlusion, and organ dysfunction. Red blood cell transfusions are a therapeutic mainstay in SCD, which can lead to iron overload and endocrine disease. However, due to diagnostic difficulties and lack of data, there is not a wide consensus in approach. This has led to many practitioners screening for endocrinopathies only once patients are symptomatic. In this study, we implemented a standardized protocol for screening of iron overload and certain endocrinopathies in a single-study cohort of patients with SCD to assess viability in real-world practice and to detect disease prior to significant burden. We studied 19 patients diagnosed with SCD or sickle-cell trait (SCT) at a single institution. Patients had serum testing for ferritin and a metabolic panel at usual clinical visits. Iron overload was diagnosed with serum ferritin levels of at least 1000 ng/mL. If iron overload was detected, additional testing for 25-Hydroxyvitamin D (OHD), Thyroid Stimulating Hormone (TSH), Parathyroid Hormone (PTH), and Insulin-Like Growth Factor-1 (IGF-1) was obtained. Nineteen patients (12 men and 7 women) were included with a mean age of 32 years old. Twelve patients and seven patients were diagnosed with SCD and SCT, respectively. The average ferritin levels of SCD and SCT patients were 4874 and 270 ng/mL, respectively. Nine patients had ferritin levels greater than 1000 ng/mL, eight of which were diagnosed with SCD, one was diagnosed with SCT, and seven of which were prescribed iron chelation therapy. Of these nine patients, the average random glucose was 103 ng/mL. The average serum calcium corrected for albumin levels was 9.3 ng/mL. Seven of eight patients were found to have low 25-OHD levels with two of four patients showing elevated serum PTH. One of six patients had abnormal thyroid testing, with an elevated TSH and normal free thyroxine. Three of five patients showed abnormal IGF-1 testing, with low IGF-1 levels and low IGF-1 binding protein levels. This study successfully implemented a protocol for screening for endocrinopathies in a cohort of SCD and SCT patients at a single institution. We showed evidence that many patients with iron overload demonstrated abnormalities in 25-OHD, PTH, TSH, and IGF-1. The few studies that have been done to analyze this topic have shown findings of growth failure, osteopenia, hypogonadism, hypothyroidism, and glucose intolerance in SCD and SCT patients. This study did not explore bone disease or sex hormone function due to difficulty in performing these tests and obtaining insurance payor coverage. An additional limitation includes low sample size. However, this study replicates real-world care for these patients due to these barriers, making these methods easily translatable to other clinical settings. Our findings suggest implementation of a standardized protocol for iron overload and endocrinopathy screening in SCD and SCT patients is not only viable but could also detect disease before symptom onset when intervention is more effective.