The effect of bone and analytical methods on the assessment of bone mineralization response to dietary phosphorus, phytase, and vitamin D in nursery pigs.

A total of 360 pigs (DNA 600 × 241, DNA; initially 11.9 ±â€…0.56 kg) were used in a 28-d trial to evaluate the effects of different bones and analytical methods on the assessment of bone mineralization response to dietary P, vitamin D, and phytase in nursery pigs. Pens of pigs (six pigs per pen) were randomized to six dietary treatments in a randomized complete block design with 10 pens per treatment. Dietary treatments were designed to create differences in bone mineralization and included: (1) 0.19% standardized total tract digestibility (STTD) P (deficient), (2) 0.33% STTD P (NRC [2012] requirement) using monocalcium phosphate, (3) 0.33% STTD P including 0.14% release from phytase (Ronozyme HiPhos 2700, DSM Nutritional Products, Parsippany, NJ), (4) 0.44% STTD P using monocalcium phosphate, phytase, and no vitamin D, (5) diet 4 with vitamin D (1,653 IU/kg), and (6) diet 5 with an additional 50 µg/kg of 25(OH)D3 (HyD, DSM Nutritional Products, Parsippany, NJ) estimated to provide an additional 2,000 IU/kg of vitamin D3. After 28 d on feed, eight pigs per treatment were euthanized for bone (metacarpal, 2nd rib, 10th rib, and fibula), blood, and urine analysis. The response to treatment for bone density and ash was dependent upon the bone analyzed (treatment × bone interaction for bone density, P = 0.044; non-defatted bone ash, P = 0.060; defatted bone ash, P = 0.068). Thus, the response related to dietary treatment differed depending on which bone (metacarpal, fibula, 2nd rib, or 10th rib) was measured. Pigs fed 0.19% STTD P had decreased (P < 0.05) bone density and ash (non-defatted and defatted) for all bones compared to 0.44% STTD P, with 0.33% STTD P generally intermediate or similar to 0.44% STTD P. Pigs fed 0.44% STTD P with no vitamin D had greater (P < 0.05) non-defatted fibula ash compared to all treatments other than 0.44% STTD P with added 25(OH)D3. Pigs fed diets with 0.44% STTD P had greater (P < 0.05) defatted second rib ash compared to pigs fed 0.19% STTD P or 0.33% STTD P with no phytase. In summary, bone density and ash responses varied depending on bone analyzed. Differences in bone density and ash in response to P and vitamin D were most apparent with fibulas and second ribs. There were apparent differences in the bone ash percentage between defatted and non-defatted bone. However, differences between the treatments remain consistent regardless of the analytic procedure. For histopathology, 10th ribs were more sensitive than 2nd ribs or fibulas for the detection of lesions.

Lameness is defined as impaired movement or deviation from normal gait. There are many factors that can contribute to lameness, including but not limited to: infectious disease, genetic and conformational anomaly, and toxicity that affects the bone, muscle, and nervous systems. Metabolic bone disease is another cause of lameness in swine production and can be caused by inappropriate levels of essential vitamins or minerals. To understand and evaluate bone mineralization, it is important to understand the differences in diagnostic results between different bones and analytical techniques. Historically, percentage bone ash has been used as one of the procedures to assess metabolic bone disease as it measures the level of bone mineralization; however, procedures and results vary depending on the methodology and type of bone measured. Differences in bone density and ash in response to dietary P and vitamin D were most apparent in the fibulas and second ribs. There were apparent differences in the percentage of bone ash between defatted and non-defatted bone; however, the differences between the treatments remain consistent regardless of the analytic procedure. For histopathology, 10th ribs were more sensitive than 2nd ribs or fibulas for detection of lesions associated with metabolic bone disease.

Metabolomics assessment of vitamin D impact in Pam3CSK4 stimulation.

Bacteria are amongst the leading causes of mortality worldwide. Although several studies have proposed the possible therapeutic role of vitamin D in bacterial infection, the exact mechanism through which vitamin D functions in antibacterial immunity remains elusive. The metabolic reconfigurations induced by vitamin D in bacterial infection can therefore be explored through metabolomics, a multidisciplinary 'omics' science that evaluates the metabolic changes of a biological system by identifying and quantifying metabolites under specific conditions. In the present study, cultured U937 macrophages were treated with Pam3CSK4/mL, 1,25(OH)2D3 and a combination of Pam3CSK4/mL and 1,25(OH)2D3. These treatment/stimulated U937 cells were compared to untreated cells in order to measure the metabolic effect of vitamin D (1,25(OH)2D3). Intracellular metabolomics was performed using nuclear magnetic resonance. The obtained data were subjected to chemometric modelling and statistical analyses, which revealed a clear distinction between the metabolic profiles of Pam3CSK4 stimulated cells, 1.25(OH)2D3 supplemented cells and cells supplemented with a combination of Pam3CSK4/1.25(OH)2D3 as compared to the untreated cells. Significant differences (p < 0.05) were identified in 32 metabolites linked to bioenergy production, redox reaction regulation, inflammation and protein synthesis. The generated results illustrate that 1.25(OH)2D3 reprogrammes the metabolic profile of U937 cells stimulated with Pam3CSK4.

Assessment of the Effects of Dietary Vitamin D Levels on Olanzapine-Induced Metabolic Side Effects: Focus on the Endocannabinoidome-Gut Microbiome Axis.

Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The gut microbiota and endocannabinoidome (eCBome) are significant regulators of both metabolism and mental health, but their role in the development of atypical antipsychotic drug metabolic side-effects and their interaction with vitamin D status is unknown. We studied the effects of different combinations of vitamin D levels and atypical antipsychotic drug (olanzapine) exposure on whole-body metabolism and the eCBome-gut microbiota axis in female C57BL/6J mice under a high fat/high sucrose (HFHS) diet in an attempt to identify a link between the latter and the different metabolic outputs induced by the treatments. Olanzapine exerted a protective effect against diet-induced obesity and insulin resistance, largely independent of dietary vitamin D status. These changes were concomitant with olanzapine-mediated decreases in Trpv1 expression and increases in the levels of its agonists, including various N-acylethanolamines and 2-monoacylglycerols, which are consistent with the observed improvement in adiposity and metabolic status. Furthermore, while global gut bacteria community architecture was not altered by olanzapine, we identified changes in the relative abundances of various commensal bacterial families. Taken together, changes of eCBome and gut microbiota families under our experimental conditions might contribute to olanzapine and vitamin D-mediated inhibition of weight gain in mice on a HFHS diet.

Balancing Altered Calcium Metabolism with Bone Health in Sarcoidosis.

Abnormal calcium metabolism in sarcoidosis patients can lead to hypercalcemia, hypercalciuria, and kidney stones. Hypercalcemia in sarcoidosis is usually due to increased activity of 1α-hydroxylase in macrophages of pulmonary granulomata, resulting in low levels of 25-hydroxyvitamin D and high levels of calcitriol. Vitamin D supplementation may be dangerous for some sarcoidosis patients and is recommended only for those with decreased 25-hydroxyvitamin D and reduced or normal calcitriol level. Diagnosis, treatment of osteoporosis, and maintenance of bone health are complex issues for sarcoidosis patients. An approach to diagnosis and treatment of bone fragility is presented.

Assessment of eldecalcitol and alendronate effect on postural balance control in aged women with osteoporosis.

INTRODUCTION: Older people aged over 75 are more prone to falls because physical functions become deteriorated along with aging, and also fracture risk is strongly correlated with age. We evaluated the effects of anti-osteoporosis agents, eldecalcitol (ELD) and alendronate (ALN) on physical functions by assessing dynamic and static postural balance in aged patients with osteoporosis. MATERIALS AND METHODS: A randomized, open-label, controlled clinical trial has been conducted with 124 female patients aged 65 or over with osteoporosis. Patients were randomly assigned to receive either 0.75 µg of ELD once-a-day or 35 mg of ALN once-a-week for 24 weeks. The primary endpoint was the change in a postural balance index, adjusted composite equilibrium score (CES) of sensory organization test (SOT). The SOT equilibrium scores, leg muscle strength, and other physical functions were also evaluated. RESULTS: The Adjusted CES increased from baseline by 6.10% in the ELD group and 6.28% in the ALN group. There was no statistically significant difference between the two groups. The static postural balance at fixed platform were maintained in the ELD group, but declined in the ALN group. The dynamic postural balance at swaying platform and knee extension power increased from baseline in both groups. CONCLUSIONS: These results suggest that ELD and ALN treatments may each be beneficial to improve postural balance control in older patients with osteoporosis via different mechanisms of action.

Effects of vitamin D in an animal model of Alzheimer's disease: behavioral assessment with biochemical investigation of Hippocampus and serum.

Regulatory role of vitamin D (VitD) in cognitive memory and learning has been proposed. Here, we examine the behavioral and biochemical effects of VitD in Alzheimer's disease (AD), as the most common form of dementia, in male Wistar rats. Animals (n = 48) were randomly divided into six groups: control, sham solvent, sham surgery, VitD (by intraperitoneal injection), AD (receiving intrahippocampal injection of amyloid-beta peptide, Aß), and combination of VitD and Aß. Learning and memory functions were investigated through the passive avoidance and the Morris water maze (MWM) tasks. Moreover, oxidative stress biomarkers including total antioxidant capacity (TAC), total thiol groups (TTG), lipid peroxidation (LPO), and DNA damage were assessed in hippocampus and serum. In passive avoidance task, Aß significantly impaired the step-through latency and time in dark compartment. It also increased escape latency and time spent in the target quadrant in the MWM. VitD administration attenuated the Aß-induced memory impairment in passive avoidance and MWM tests. Furthermore, VitD reduced deleterious biochemical effect of Aß by enhancing the levels of TAC and TTG in addition to decreasing LPO and DNA damage levels in both hippocampus and serum. We showed, for the first time, that VitD administration improves the impaired Aß-induced memory and that, by acting as a strong antioxidant, it can attenuate the stress oxidative biomarkers in hippocampus and serum of rats with AD. Altogether, our results provide evidence for further application of VitD in neurodegenerative disorders such as AD to enlighten the involved mechanisms.

Is vitamin D-fortified yogurt a value-added strategy for improving human health? A systematic review and meta-analysis of randomized trials.

Yogurt is a good source of probiotics, calcium, and proteins, but its content of vitamin D is low. Therefore, yogurt could be a good choice for vitamin D fortification to improve the positive health outcomes associated with its consumption. The primary aim of this systematic review and meta-analysis was to investigate the effect of vitamin D-fortified yogurt compared with plain yogurt on levels of serum 25-hydroxy vitamin D (25OHD). The secondary aim was to evaluate the effect of fortified yogurt on parathyroid hormone, anthropometric parameters, blood pressure, glucose metabolism, and lipid profile. We searched PubMed, Scopus, and Google Scholar for eligible studies; that is, randomized controlled trials (RCT) that compared vitamin D-fortified yogurt with control treatment without any additional supplement. Random-effects models were used to estimate pooled effect sizes and 95% confidence intervals. Findings from 9 RCT (n = 665 participants) that lasted from 8 to 16 wk are summarized in this review. The meta-analyzed mean differences for random effects showed that vitamin D-fortified yogurt (from 400 to 2,000 IU) increased serum 25OHD by 31.00 nmol/L. In addition, vitamin D-fortified yogurt decreased parathyroid hormone by 15.47 ng/L, body weight by 0.92 kg, waist circumference by 2.01 cm, HOMA-IR by 2.18 mass units, fasting serum glucose by 22.54 mg/dL, total cholesterol by 13.38 mg/dL, and triglycerides by 30.12 mg/dL compared with the controlled treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes. Vitamin D-fortified yogurt may be beneficial in improving serum 25OHD, lipid profile, glucose metabolism, and anthropometric parameters and decreasing parathyroid hormone level in pregnant women and adult and elderly subjects with or without diabetes, prediabetes, or metabolic syndrome.

Assessment of Vitamin D Supplementation on Articular Cartilage Morphology in a Young Healthy Sedentary Rat Model.

Deficiency in vitamin D (Vit D) has been widely associated with several musculoskeletal diseases. However, the effects of the exogenous Vit D supplementation are still unclear in the prevention of the latter, especially in the cartilage developmental period. The aim of this study was to compare the effects of Vit D supplementation and restriction on the articular cartilage development in healthy young sedentary rats. To this aim, twelve nine-week-old healthy Sprague-Dawley male rats were subjected to Vit D-based experimental diets: R, with a content in Vit D of 1400 IU/kg; R-DS, with a Vit D supplementation (4000 IU/kg); R-DR, with a Vit D restriction (0 IU/kg) for 10 weeks. The morphology, thickness and expression of cartilage-associated molecules such as collagen type II/X, lubricin and Vit D receptor (VDR), were assessed. Histological, histomorphometric and immunohistochemical evaluations were made on rat tibial cartilage samples. In the present experimental model, restriction of Vit D intake induced: The lower thickness of cartilage compared both to R (p = < 0.0001) and R-DS (p = < 0.0001); reduction of proteoglycans in the extracellular matrix (ECM) compared both to R (p = 0.0359) and R-DS (p = < 0.0001); decreased collagen II (Col II) with respect both to R (p = 0.0076) and R-DS (p = 0.0016); increased collagen X (Col X) immunoexpression when compared both to R (p = < 0.0001) and R-DS (p = < 0.0001), confirming data from the literature. Instead, supplementation of Vit D intake induced: Higher cartilage thickness with respect both to R (p = 0.0071) and R-DR (p = < 0.0001); increase of ECM proteoglycan deposition compared both to R (p = 0.0175) and R-DR (p = < 0.0001); higher immunoexpression of lubricin with respect both to R (p = 0.001) and R-DR (p = 0.0008). These results suggest that Vit D supplementation with diet, already after 10 weeks, has a favorable impact on the articular cartilage thickness development, joint lubrication and ECM fibers deposition in a young healthy rat model.

The effect of vitamin D on cognitive functions in young female patients: a prospective controlled study using the Montreal Cognitive Assessment.

AIM: Our aim was to determine whether there is a relationship between vitamin D [25(OH)D] and cognitive functioning in women with low 25(OH)D levels. METHODS: Ninety female patients, 25-45 years of age, who attended our outpatient clinic and had 25(OH)D levels < 30 ng/mL, were included. The Montreal Cognitive Assessment (MoCA) scale was used to determine cognitive functioning; the scale is divided into seven subgroups. Patients were divided into three subgroups according to their 25(OH)D levels. After a three-month period of 25(OH) D replacement, the patients underwent a re-evaluation using the MoCA scale. RESULTS: The total MoCA score before treatment was significantly different from the score after treatment (p < 0.05). Language and delayed recall functions were significantly different before and after treatment (p < 0.05). CONCLUSION: Vitamin D levels were related to cognitive functioning in our study group.

The effect of vitamin D on cognitive functions in young female patients: a prospective controlled study using the Montreal Cognitive Assessment / O efeito da vitamina D nas funções cognitivas em pacientes jovens do sexo feminino: um estudo prospectivo controlado usando a avaliação cognitiva de Montreal

ABSTRACT Aim: Our aim was to determine whether there is a relationship between vitamin D [25(OH)D] and cognitive functioning in women with low 25(OH)D levels. Methods: Ninety female patients, 25-45 years of age, who attended our outpatient clinic and had 25(OH)D levels < 30 ng/mL, were included. The Montreal Cognitive Assessment (MoCA) scale was used to determine cognitive functioning; the scale is divided into seven subgroups. Patients were divided into three subgroups according to their 25(OH)D levels. After a three-month period of 25(OH) D replacement, the patients underwent a re-evaluation using the MoCA scale. Results: The total MoCA score before treatment was significantly different from the score after treatment (p < 0.05). Language and delayed recall functions were significantly different before and after treatment (p < 0.05). Conclusion: Vitamin D levels were related to cognitive functioning in our study group.

RESUMO Objetivo: Nosso objetivo foi determinar se existe uma relação entre a vitamina D [25(OH)D] e o funcionamento cognitivo em mulheres com baixos níveis de 25(OH)D. Métodos: Noventa pacientes do sexo feminino (25-45 anos de idade) que se apresentaram ao nosso ambulatório e tinham níveis de 25(OH)D <30 ng/mL foram incluídas. A escala de avaliação cognitiva de Montreal (MoCA) foi usada para determinar o funcionamento cognitivo; a escala é dividida em sete subgrupos. As pacientes foram divididas em três subgrupos de acordo com seus níveis de 25(OH)D. Após um período de três meses de reposição de 25(OH)D, as pacientes foram submetidas a uma reavaliação de acordo com a escala MoCA. Resultados: O escore total da MoCA antes do tratamento foi significativamente diferente do escore após o tratamento (p <0,05). As funções de idioma e recordação atrasada foram mais significativamente diferentes entre antes e depois do tratamento (p <0,05). Conclusão: O nível de vitamina D foi relacionado ao funcionamento cognitivo em nosso grupo de estudo.

Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial.

Importance: Previous randomized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence. Objective: To examine whether high-dose vitamin D supplementation received monthly, without calcium, is associated with a reduction in cancer incidence and cancer mortality in the general population. Design, Setting, and Participants: This is a post hoc analysis of data from the Vitamin D Assessment (ViDA) study, a randomized, double-blind, placebo-controlled trial that recruited participants from family practices and community groups in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up completed December 31, 2015. Participants were adult community residents aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants withdrew consent, and all others (n = 5108) were included in the primary analysis. Data analysis was by intention to treat. Interventions: Oral vitamin D3, in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). Main Outcomes and Measures: Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms (excluding nonmelanoma skin cancers) diagnosed from randomization until the study medication was discontinued on July 31, 2015. Results: Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 58.1% were male, and 4253 (83.3%) were of European or another race/ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 (9.0) ng/mL. In a random sample of 438 participants, the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of cancer comprised 328 total cases of cancer (259 invasive and 69 in situ malignant neoplasms) and occurred in 165 of 2558 participants (6.5%) in the vitamin D group and 163 of 2550 (6.4%) in the placebo group, yielding an adjusted hazard ratio of 1.01 (95% CI, 0.81-1.25; P = .95). Conclusions and Relevance: High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer. This study suggests that daily or weekly dosing for a longer period may require further study. Trial Registration: anzctr.org.au Identifier: ACTRN12611000402943.

Current concepts regarding calcium metabolism and bone health in sarcoidosis.

PURPOSE OF REVIEW: Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. RECENT FINDINGS: Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. SUMMARY: Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

Vitamin D status correction in Saudi Arabia: an experts' consensus under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (ESCEO).

BACKGROUND: Vitamin D deficiency is common in the Middle East and in Saudi Arabia, in particular. While several international recommendations on the management of vitamin D deficiency have been documented and practiced globally, these recommendations should be adapted to the conditions of the Middle Eastern region. To address this challenge, the Prince Mutaib Chair for Biomarkers of Osteoporosis (PMCO) in King Saud University (KSU), Riyadh, KSA, together with local experts and in cooperation with the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), organized a panel that formulated unified recommendations in the diagnosis and treatment of vitamin D deficiency in the region. METHODS: The selection of local and international experts commenced during the 2nd International Vitamin D Symposium conducted in Riyadh, Saudi Arabia, last January 20--21, 2016. Reviews of the most recent literature were done, and face-to-face meetings were conducted for revisions and final recommendations. RESULTS: Vitamin D sufficiency is defined as circulating serum 25(OH)D ≥50 nmol (≥20 ng/ml) for the general population and vitamin D adequacy as serum 25(OH)D >75 nmol/L l (>30 ng/ml) for the frail and osteoporotic elderly. Despite overwhelming prevalence of vitamin D deficiency, universal screening is not recommended. Recommendations for the general population, children, pregnant/lactating women, post-menopausal women, the elderly, and those with subsequent metabolic diseases were provided. RESULTS: Vitamin D sufficiency is defined as circulating serum 25(OH)D ≥50 nmol (≥20 ng/ml) for the general population and vitamin D adequacy as serum 25(OH)D >75 nmol/L l (>30 ng/ml) for the frail and osteoporotic elderly. Despite overwhelming prevalence of vitamin D deficiency, universal screening is not recommended. Recommendations for the general population, children, pregnant/lactating women, post-menopausal women, the elderly, and those with subsequent metabolic diseases were provided. CONCLUSION: Vitamin D supplementation/correction is advised in all persons whose serum 25(OH)D falls below 50 nmol/l (20 ng/ml), and achieving a target of 75 nmol/l (30 ng/ml) is particularly suited for frail, osteoporotic, and older patients. Conducting well-designed clinical trials in the region that will address economic implications and investigations on the treatment persistence and compliance to vitamin D treatment in the region are encouraged.

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial.

BACKGROUND: Some observational studies have suggested that higher prenatal Vitamin D intake may be associated with improved health outcomes in childhood. However there have been mixed results in this area with some negative studies, especially for effects on atopic and respiratory outcomes. We examined the effect of prenatal Vitamin D on healthcare utilisation in the first three years of life. METHODS: In an ethnically stratified randomised controlled trial conducted at St Mary's Hospital London, 180 women at 27 weeks gestation were allocated to no Vitamin D, 800 IU ergocalciferol daily until delivery, or a single oral bolus of 200,000 IU cholecalciferol. Participants were randomised in blocks of 15 using computer-generated numbers and investigators were blinded to group assignment. Supplementation increased maternal and cord blood 25(OH) vitamin D concentrations, but levels remained lower than current recommendations. Primary health economic outcome was overall cost of unscheduled healthcare utilisation in the first three years of life as documented in the child's electronic health record. Secondary outcomes included cost attributable to: primary and secondary healthcare visits, respiratory and atopic complaints, cost in years 1, 2 and 3 of life and cost and frequency of prescribed medication. All costs were calculated as pounds sterling. Differences between groups were analysed using unpaired t-test or Mann-Whitney U test, and analysis of variance for adjusted analyses. RESULTS: We assessed 99/180 (55%) complete electronic health records, control (n = 31), daily (n = 36) and bolus (n = 32). We found no difference in total healthcare utilisation costs between the control and daily (mean difference in costs in pounds sterling 1.02, 95%CI -1.60, 1.65; adjusted 1.07, 95%CI -1.62, 1.86) or control and bolus groups (mean difference -1.58, 95%CI -2.63, 1.06; adjusted -1.40, 95%CI -2.45, 1.24). There were no adverse effects of supplementation reported during the trial. CONCLUSIONS: We found no evidence that prenatal vitamin D supplementation from 27 weeks gestation to delivery, at doses which failed to completely correct maternal vitamin D deficiency, influence overall healthcare utilisation in children in the first 3 years. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN68645785.

Comparison of cost-effectiveness of vitamin D screening with that of universal supplementation in preventing falls in community-dwelling older adults.

OBJECTIVES: To compare the cost-effectiveness of population screening for vitamin D insufficiency with that of universal vitamin D supplementation in community-dwelling older adults. DESIGN: A Markov decision model simulating follow-up over a 36-month period. Published data were used to estimate values for the model, including costs (measured in 2011 U.S. dollars), utilities (measured in quality-adjusted life years (QALYs)), and probabilities. SETTING: Decision analysis simulation from a societal perspective. PARTICIPANTS: Hypothetical cohort of community-dwelling women and men aged 65 to 80. MEASUREMENTS: Net monetary benefit (NMB) was calculated by subtracting the incremental cost of the strategy from the product of incremental QALYs and willingness-to-pay threshold. A higher NMB indicates greater cost-effectiveness. RESULTS: In women aged 65 to 80, population screening was slightly more cost-effective than universal supplementation, with an incremental NMB of $224 compared with $189 (P < .001). Population screening in men was also more cost-effective than universal supplementation (incremental NMB $298 vs $260, P < .001). Results differed according to age group. In those aged 65, population screening had cost-effectiveness similar to that of universal supplementation in women ($59 vs $71) and men ($114 vs $120), whereas in those aged 80, population screening was substantially more cost-effective than universal supplementation in women ($563 vs $428) and men ($703 vs $571). CONCLUSION: Population screening and universal supplementation for vitamin D insufficiency are cost-effective strategies in community-dwelling older women and men. In the oldest old, population screening may be more cost-effective than universal supplementation.

Assessment of the potential role of active vitamin D treatment in telomere length: a case-control study in hemodialysis patients.

BACKGROUND: Telomeres are special chromatin sequences located at the end of eukaryotic chromosomes, protecting these regions from recombination and degradation. Previous studies have reported a decrease in telomere length on white blood cells from hemodialysis (HD) patients, which suggests premature senescence. Active vitamin D treatment has been reported to have an effect on telomere length and beneficial effects on HD patients, but the mechanisms are unknown. OBJECTIVE: Our aim was to assess the potential protective role of active vitamin D treatment on telomere length in peripheral mononuclear cells (PBMC) from HD patients. METHODS: A retrospective case-control study of 62 stable HD patients and 60 healthy sex-matched controls was undertaken. Telomere length was measured in PBMC by Southern blot. After telomere length measurement, 5 control samples that did not reach quality-control standards were excluded. Standard epidemiological and biochemical parameters were recorded. Blood biochemistries were performed at the Biochemistry Department of the University Hospital Arnau de Vilanova in Lleida, Spain, using standard routine techniques. Differences in telomere length were analyzed using Student's t test. Multiple regression analysis examined the independent contribution of the factors that significantly affected telomere length in the bivariate analysis. RESULTS: HD patients presented shorter telomere length in PBMC, independent of age and sex (mean [SD] 8.8 [1.5] kbp vs 10.5 [2.9] kbp; P = 0.0001). Multivariate regression analysis of the HD subgroup suggested that patients under active vitamin D treatment have greater telomere length in PBMC than untreated patients (9.5 [0.2] kbp vs 8.4 [0.2] kbp; P = 0.003). CONCLUSIONS: HD patients were observed to have decreased PBMC telomere length compared with healthy controls. HD patients treated with active vitamin D compounds had greater PBMC telomere length than untreated patients. Prospective studies are required to assess the potential role of active vitamin D treatment in PBMC telomere length.

Effect of eldecalcitol, an active vitamin D analog, on hip structure and biomechanical properties: 3D assessment by clinical CT.

The effects of an active vitamin D analog, eldecalcitol (ELD), on bone mineral density (BMD), bone geometry, and biomechanical properties of the proximal femur were investigated by using clinical CT. The subjects--a subgroup of a recent randomized, double-blind study comparing anti-fracture efficacy of ELD with alfacalcidol (ALF) - constituted 193 ambulatory patients with osteoporosis (189 postmenopausal women and 4 men aged 52-85 years, average ± SD: 70.9 ± 6.92 years) enrolled at 11 institutions. Multidetector-row CT data was acquired at baseline and at completion of 144 weeks' treatment. Cross-sectional densitometric and geometric parameters of the femoral neck were derived from three-dimensional CT data. Biomechanical properties including cross-sectional moment of inertia (CSMI), section modulus (SM) and buckling ratio (BR) of the femoral neck, and CSMI of the femoral shaft were also calculated. We found that, (1) with respect to the femoral neck cross-sectional parameters (total bone), in the ALF group, volumetric BMD (vBMD) decreased but bone mass was maintained and cross-sectional area (CSA) increased. In contrast, ELD maintained vBMD with a significant increase in bone mass and a trend toward increased CSA. (2) With respect to the femoral neck cross-sectional parameters (cortex), cortical thickness decreased in the ALF group, but was maintained in the ELD group. In the ALF group, vBMD and bone mass increased, and CSA was maintained. In the ELD group, vBMD, CSA, and bone mass increased. (3) With respect to the biomechanical properties of the femoral neck, ELD improved CSMI and SM to a greater extent than did ALF. BR increased in both the ALF and ELD groups. (4) With respect to the femoral shaft parameters, overall the results of bone geometry and CSMI of the femoral shaft were very consistent with the results for the femoral neck; however, cortical vBMD of the femoral shaft decreased significantly in both the ELD and ALF groups. In conclusion, our longitudinal analysis of hip geometry by clinical CT revealed the unexpected potential of ELD to increase cortical CSA, vBMD, and bone mass, and to maintain cortical thickness, probably through the more potent effect of ELD in mitigating endocortical bone resorption than ALF. By improving the biomechanical properties of the proximal femur, ELD may have the potential to reduce the risk of hip fractures.

Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans.

Vitamin D regulates the renin-angiotensin system (RAS) in experimental animals, but corresponding human data are limited. We examined the relation between plasma 25-hydroxyvitamin D and elements of the RAS in 184 normotensive individuals in high sodium balance; these included circulating levels of plasma renin activity and angiotensin II (Ang II) and the renal plasma flow response to infused Ang II, which is an indirect measure of the intrinsic RAS activity in the kidney. Compared with individuals with sufficient 25-hydroxyvitamin D levels (> or = 30.0 ng/mL), those with insufficiency (15.0 to 29.9 ng/mL) and deficiency (<15.0 ng/mL) had higher circulating Ang II levels (P for trend=0.03). Moreover, those with vitamin D deficiency had significantly blunted renal plasma flow responses to infused Ang II (mean decrease of 115 mL/min per 1.73 m(2) in renal plasma flow versus 145 mL/min per 1.73 m(2) among those with sufficient vitamin D levels; P for trend=0.009). Although plasma renin activity was higher among individuals with insufficient levels of vitamin D, the result was not statistically significant. These data suggest that low plasma 25-hydroxyvitamin D levels may result in upregulation of the RAS in otherwise healthy humans.

Clinical issues regarding cinacalcet hydrochloride in Japan.

Currently available cinacalcet hydrochloride has a greater advantage over conventional vitamin D therapy, although the ability of cinacalcet to suppress parathyroid hormone (PTH) varies among individuals. This article deals with the clinical issues of cinacalcet. Studies examining the impact of cinacalcet on parathyroid gland cells showed that cinacalcet may cause changes in PTH secretion, reduce the parathyroid gland size, and alter parathyroid gland function, suggesting the possibility that use of cinacalcet can eventually be stopped. Combined cinacalcet and vitamin D can reportedly increase vitamin D receptor expression. In a double-blind, placebo-controlled randomized study involving 1184 previously untreated secondary hyperparathyroidism (SHPT) patients, cinacalcet significantly reduced the likelihood of hospitalization for parathyroidectomy, fractures, and cardiovascular disease. Fibrous osteitis was suppressed in the rat model of renal failure treated with cinacalcet. Considering that the drug price of cinacalcet is lower in Japan than in the USA and Europe, it is highly likely that cinacalcet will be used to suppress PTH in Japan.

Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe.

Vitamin D has important benefits in reducing the risk of many conditions and diseases. Those diseases for which the benefits are well supported and that have large economic effects include many types of cancer, cardiovascular diseases, diabetes mellitus, several bacterial and viral infections, and autoimmune diseases such as multiple sclerosis. Europeans generally have low serum 25-hydroxyvitamin D [25(OH)D] levels owing to the high latitudes, largely indoor living, low natural dietary sources of vitamin D such as cold-water ocean fish, and lack of effective vitamin D fortification of food in most countries. Vitamin D dose-disease response relations were estimated from observational studies and randomized controlled trials. The reduction in direct plus indirect economic burden of disease was based on increasing the mean serum 25(OH)D level to 40 ng/mL, which could be achieved by a daily intake of 2000-3000 IU of vitamin D. For 2007, the reduction is estimated at euro187,000 million/year. The estimated cost of 2000-3000 IU of vitamin D3/day along with ancillary costs such as education and testing might be about euro10,000 million/year. Sources of vitamin D could include a combination of food fortification, supplements, and natural and artificial UVB irradiation, if properly acquired. Additional randomized controlled trials are warranted to evaluate the benefits and risks of vitamin D supplementation. However, steps to increase serum 25(OH)D levels can be implemented now based on what is already known.