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Abstract Objective: To estimate the prevalence of vitamin D deficiency and severe deficiency in children and adolescents, in a large Brazilian sample. Methodology: Results of 413,988 25(OH)D measurements in children and adolescents aged 0 to 18 years collected between 01/2014 and 10/2018 were obtained from the database of a Clinical Laboratory. In this population, 25 hydroxyvitamin D concentrations below 20 ng/mL are considered deficient, and below 12 ng/mL as severe deficiency. All measurements were performed by immunoassay and the results were distributed by gender, age group, seasonality, and latitude. Results: The mean of 25(OH)D levels was 29.2 ng/mL with a standard deviation of 9.2 ng/mL. Of the total samples, 0.8% had a concentration < 12 ng/mL, and 12.5% of the samples had a concentration < 20 ng/mL, with a higher prevalence in females. Children under 2 years of age had the lowest prevalence. The effects of latitude and seasonality were quite evident. In samples of female adolescents from the southern region in winter, 36% of vitamin D deficiency and 5% of severe deficiency were found. Conclusion: In this large number of measurements of 25(OH)D in children and adolescents, 12.5% had a deficiency and 0.8% had severe deficiency. A greater deficiency was observed among adolescents, especially females, which raises questions about the need for supplementation during this period of life.

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BACKGROUND: Vitamin D may prevent the development of hypertension through down-regulation of renin-angiotensin system. However, epidemiologic studies assessing the interrelation of vitamin D-related biomarkers with hypertension are sparse. METHODS: We examined the prospective associations between vitamin D-related biomarkers and risk of hypertension in a nested case-control study. In each of the Women's Health Study (WHS) and Physicians' Health Study (PHS) II, 500 incident hypertension cases and 500 age and race matched controls were randomly selected. Baseline plasma 25(OH)-vitamin D [25(OH)D], parathyroid hormone (PTH), and total renin concentrations were measured. RESULTS: Among controls, 25(OH)D and PTH were inversely correlated, but neither was correlated with total renin. In the crude model, there was a trend of association between increasing quintiles of 25(OH)D and lower risk of hypertension in women, with relative risks and 95% CIs of 1.00, 1.24 (0.84-1.83), 0.82 (0.53-1.25), 0.75 (0.48-1.16), and 0.81 (0.52-1.27) (p, trend: 0.07). Adjustment for body mass index and other hypertension risk factors eliminated this association (RR of 5th quintile: 1.03). No associations were found in men. Baseline PTH and ratio of 25(OH)D to PTH were not associated with risk of hypertension in women or men. When men and women were included in the same model, vitamin D insufficiency (defined as 25(OH)D <20 ng/mL) also was not associated with increased risk of hypertension. No interactions were found across subgroups. CONCLUSIONS: Our study found no association of baseline plasma 25(OH)D or PTH with risk of hypertension or total renin concentration in middle-aged and older men and women.

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The aim of this study was to validate an HPLC-UV method to assess vitamin D status by determining the linearity and precision of the 25-hydroxyvitamin D3 (25(OH)D3) calibration curve, the limits of detection, quantitation and robustness of the method, and its accuracy. A second stock solution of 25(OH)D3 was prepared (500 ng/mL), and working dilutions (5, 10, 20, 30, 40, and 50 ng/mL) were prepared for a calibration curve. The HPLC equipment had a UV-Vis diode-array detector and utilized an AcclaimTM 120 C18 column (5 µm, 4.6 × 250 mm) with a flow rate of 1.2 mL/min, a column temperature of 30 °C, and the standards and samples were maintained at 4 °C, with an injection volume of 100 µL. Detection of 25(OH)D3 was determined at 265 nm, with a retention time of 4.0 min. The validation was conducted according to the FDA Validation of Analytical Procedures: Guidance for Industry. Vitamin D was extracted from plasma samples using acetonitrile (ACN)-0.1% formic acid (2:1 v/v), and the percentage of recovery was calculated. The proposed method conditions gave excellent linearity (R2 = 0.9989) and the linearity coefficient was R2 > 0.99 for 25(OH)D3. The detection and quantification limits were 1.1703 ng/mL and 3.5462 ng/mL, respectively. Decreasing or increasing the reading temperature by 1 °C decreased the response units (AU) of vitamin D, 25(OH)D3. When the current flow rate decreased by 0.2 mL/min (1.0 mL/min), the retention time increased to 4.913 min, whereas an increase of 0.2 mL/min of the proposed flow rate (1.4 mL/min) decreased the retention time to 3.500 min. The percentage of recovery varied from 92.2% to 97.1%. The proposed method to quantify a vitamin D metabolite (25(OH)D3) in human plasma samples was reliable and validated.

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PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

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OBJECTIVE: To estimate the prevalence of vitamin D deficiency and severe deficiency in children and adolescents, in a large Brazilian sample. METHODOLOGY: Results of 413,988 25(OH)D measurements in children and adolescents aged 0 to 18 years collected between 01/2014 and 10/2018 were obtained from the database of a Clinical Laboratory. In this population, 25 hydroxyvitamin D concentrations below 20 ng/mL are considered deficient, and below 12 ng/mL as severe deficiency. All measurements were performed by immunoassay and the results were distributed by gender, age group, seasonality, and latitude. RESULTS: The mean of 25(OH)D levels was 29.2 ng/mL with a standard deviation of 9.2 ng/mL. Of the total samples, 0.8% had a concentration < 12 ng/mL, and 12.5% of the samples had a concentration < 20 ng/mL, with a higher prevalence in females. Children under 2 years of age had the lowest prevalence. The effects of latitude and seasonality were quite evident. In samples of female adolescents from the southern region in winter, 36% of vitamin D deficiency and 5% of severe deficiency were found. CONCLUSION: In this large number of measurements of 25(OH)D in children and adolescents, 12.5% had a deficiency and 0.8% had severe deficiency. A greater deficiency was observed among adolescents, especially females, which raises questions about the need for supplementation during this period of life.

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Individuals with low levels of vitamin D are associated with cardiovascular risks, such as elevated blood pressure (BP), and are; therefore, more likely to develop hypertension. Patients with vitamin D deficiency may face an increased risk of cardiovascular events. In this study, a multicenter, cross-sectional, and school-based investigation was conducted as part of the ERICA project. The sample comprised 1152 adolescents aged 12-17 years from 4 Brazilian cities. Anthropometric variables, BP measurements, and hydroxyvitamin D concentrations were assessed. A 2-level linear regression was fitted to examine the relationship between each level of BP and independent variables. Our findings indicate that movement behaviors were not associated with BP levels, with the exception of sleep time, which demonstrated a positive association. However, after adjustment, this association was found to be nonsignificant. Our study's mediation analysis revealed that vitamin D mediates up to 12.9% of the association between physical activity and systolic BP. Vitamin D is inversely associated with BP in adolescents. In addition to mediating the physical activity and systolic BP association, engaging in physical activity, particularly outdoors, can provide a dual benefit for adolescents by increasing serum vitamin D levels and assisting in the control of BP levels.

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ABSTRACT Purpose: This study aimed to investigate the correlation between serum vitamin D levels and disease activity in patients with noninfectious uveitis. Methods: We conducted a prospective case-control study, assessing 51 patients with noninfectious uveitis, categorized into active (n=22) and inactive (n=29) groups, along with 51 healthy controls. Serum 25-hydroxy vitamin D [25(OH)D] levels were measured. The uveitis group also completed a questionnaire regarding sunlight exposure habits and vitamin D supplementation. Results: Patients with inflammation-related uveitis exhibited low serum 25(OH)D levels in 68% of cases. The median 25(OH)D level in patients with active uveitis was 17.8 ng/mL (interquartile range [IQR], 15-21 ng/mL), significantly lower compared to the 31.7 ng/mL (IQR, 25-39 ng/mL) in patients with inactive uveitis (p<0.001) and the 27 ng/mL (IQR, 23-31 ng/mL) in the Control Group (p<0.001). Significantly, nearly all patients with uveitis taking vitamin D supplementation were in the Inactive Group (p<0.005). Moreover, reduced sunlight exposure was associated with active uveitis (p<0.003). Furthermore, patients with 25(OH)D levels below 20 ng/mL had ten times higher odds of developing active uveitis (p=0.001). Conclusions: This study revealed a prevalent 25(OH)D deficiency among patients with noninfectious uveitis and suggested a link between low 25(OH)D levels and disease activity. To prevent future episodes of intraocular inflammation, vitamin D supplementation and controlled sunlight exposure could be viable options.

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Recent scientific evidence suggests a close relationship between estrogen deficiency and vitamin D- related genes. Estrogen and vitamin D were involved with alterations in odontogenesis and tooth eruption process. Objective: The aim of the present study was to evaluate the influence of estrogen deficiency on the expression of genes related to the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model. Material and Methods: This is an experimental clinical study that used female Wistar Hannover rats. The animals were randomly divided into two groups according to the intervention received: Hypoestrogenism Group ­ animals submitted to estrogen deficiency by ovariectomy surgery and Control Group ­ animals submitted to sham surgery. Surgical intervention was performed in the prepubertal period; the animals were followed throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the mRNA expression of the vitamin D-related genes AMDHD1, CYP24A1, NADSYN1 and SEC23A in the odontogenic region of incisors through real time PCR. Student's t test was used to compare means. Kruskal-Wallis test and Dunn's posttest were also used. The level of significance was 5%. Results: SEC23A was overexpressed in the estrogen deficiency condition in the odontogenic region (p=0.021). Conclusion: Estrogen deficiency may influence the expression of the SEC23A gene involved in the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model(AU)

Evidências científicas recentes sugerem uma estreita relação entre a deficiência de estrógeno e os genes relacionados à vitamina D. O estrógeno e a vitamina D estão envolvidos com alterações na odontogênese e no processo de erupção dentária. Objetivo: O objetivo do presente estudo foi avaliar a influência da deficiência de estrógeno na expressão de genes relacionados à ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino. Material e Métodos: Trata-se de um estudo clínico experimental que utilizou ratas Wistar Hannover fêmeas. Os animais foram divididos aleatoriamente em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo ­ animais submetidos à deficiência de estrógeno pela cirurgia de ovariectomia e Grupo Controle ­ animais submetidos à cirurgia simulada. A intervenção cirúrgica foi realizada no período pré-púbere; os animais foram acompanhados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão de mRNA dos genes AMDHD1, CYP24A1, NADSYN1 e SEC23A, relacionados à vitamina D, na região odontogênica de incisivos por meio de PCR em tempo real. O teste t de Student foi utilizado para comparar as médias. Também foram utilizados o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: SEC23A foi superexpresso na condição de deficiência de estrógeno na região odontogênica (p=0,021). Conclusão: A deficiência de estrógeno pode influenciar a expressão do gene SEC23A envolvido na ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino (AU)

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Introduction: Differential diagnoses between essential tremor and Parkinson's disease is challenging in some individuals, with both disorders sharing similarities. Considering these links, we hypothesized that both conditions have a similar profile for some antioxidant molecules, including 25-hydroxyvitamin D and bilirubin. Methods: We performed a cross-sectional study comparing serum levels of 25-hydroxyvitamin D and bilirubin in 31 ET patients, 38 PD, and 65 controls matched for age. We used the Fahn-Tolosa-Marin scale for the severity of tremors in the ET group. We used Hohen-Yahr and MDS-UPDRS part III scales in the PD group. In addition, we evaluated sociodemographic characteristics, including age, sex, ethnicity, years of study, duration of disease, and use of primidone. Results: We found no differences in serum levels for 25-hydroxyvitamin D or bilirubin subtype levels between the ET and PD groups. We found low levels of indirect bilirubin in the PD group compared to the controls. We did not find differences between ET and controls in all biomarkers of the study. Conclusion: ET and PD patients have similar profiles for 25-hydroxyvitamin D and bilirubin serum levels. The discovery of differences in oxidative stress biomarkers in both conditions, mainly low-cost substances available clinically, can assist in the differential diagnosis and, in the future, prognostication and better therapy management (AU).

Introdução: O diagnóstico diferencial entre tremor essencial (TE) e a doença de Parkinson (DP) é desafiador em alguns indivíduos com ambas as afecções apresentando algumas similaridades. Assim sendo, hipotetizamos que ambas têm perfil similar de algumas moléculas antioxidantes, incluindo 25-hidroxivitamina D e bilirrubina. Méto-dos: Realizamos um estudo transversal comparando os níveis séricos de 25-hidroxivitamina D e bilirrubinas em 31 indivíduos com TE, 38 com DP e 65 controles pareados por idade. A escala de Fahn-Tolosa-Marin foi usada para avaliação da gravidade do tremor no grupo com TE e Hohen-Yahr e UPDRS parte III na avaliação do grupo com DP. Também foram avaliadas as características sociodemográficas. Resultados: Não encontramos diferenças nos níveis séricos de 25-hidroxivitamina D ou bilirrubina entre os grupos TE e DP. Encontramos baixos níveis de bilirrubina indireta no grupo DP comparado aos controles. Não encontramos diferenças entre os grupos com TE e controles em nenhum dos biomarcadores do estudo. Conclusão: Pacientes com TE e DP apresentam níveis séricos semelhantes de 25-Hidroxivitamina D e bilirrubinas. Diferenças nos biomarcadores de estresse oxidativo em ambas as condi-ções, principalmente substâncias de baixo custo disponíveis na clínica, pode auxiliar no diagnóstico diferencial e, futuramente, no prognóstico e otimização terapêutica (AU).

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Objective: This study investigated the nutritional status, 25-hydroxyvitamin D (25OHD), albumin and risk factors associated with complications in patients with foot and ankle fragility fractures. Subjects and methods: Prospective study, developed with patients who suffered fractures due to fragility of the foot and ankle (n = 108); the type of fractured bone, fracture mechanisms and classification were studied and also pseudoarthrosis, treatment, surgical dehiscence, anthropometry, 25OHD and albumin. The Chi-square or Fisher's exact test, Mann-Whitney and Kruskal-Wallis tests were used in the statistical analysis and the multiple logistic regression analysis was used to identify the risk factors associated with complications. Results: The factors that, together, were associated with treatment complications were the level of 25OHD (p = 0.0055; OR = 0.868 [1,152]; 95% CI = 0.786; 0.959 [1.043;1.272]) and diabetes (p = 0.0034; OR = 30,181; 95% CI = 3.087; 295.036). The factors that, together, were associated with the presence of any complication, were age (p = 0.0139; OR = 1.058; 95% CI = 1.011; 1,106) and 25OHD level (p = 0.0198; OR = 0.917; 95% CI = 0.852; 0.986). There was a complication probability above 0.40 associated with lower 25OHD levels (values below 20 ng/mL) and older age (over 50 years). Conclusion: Lower or abnormal levels of 25OHD were associated with pseudoarthrosis, and age and 25OHD were both risk factors for treatment complications in patients with foot and ankle fractures.

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