Brain changes in neuroimaging of adult patients with vitamin D deficiency: systematic review protocol.

INTRODUCTION: Brain abnormalities detected through neuroimaging are described in patients with vitamin D deficiency, however, it is still not clear which cerebral alterations are more frequent and characteristic in this population. Thus, this review aims to identify and classify which are the main and most frequent brain changes found by neuroimaging in patients with vitamin D deficiency. METHODS AND ANALYSIS: The study protocol was constructed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the leading research question was formulated through Population, Intervention, Comparator, Outcome, Setting. The evidence will be researched at the following electronic databases: PubMed, PsycINFO, Scopus, Web of Science and EMBASE. Two researchers will work in the selection, analysis and inclusion phases of the articles. In the case of divergence, a third-party reviewer will be contacted. The following studies will be included: (1) cohort studies, case-control studies and cross-sectional studies; (2) studies carried out on patients with serum 25-hydroxyvitamin D levels below 30 ng/mL; (3) studies conducted with an adult population; (4) studies using neuroimaging methods. Articles considered eligible will be analysed by the Newcastle-Ottawa Quality Assessment Scale/cross-section studies to evaluate study quality. The survey will be conducted from June to December 2022. ETHICS AND DISSEMINATION: The identification of the main and most frequent brain alterations found through neuroimaging in patients with vitamin D deficiency can guide professionals as to the identification which of the main cerebral pathologies detected through neuroimaging are related to vitamin D deficiency, in choosing more sensitive and specific neuroimaging tests to detect these brain changes, in addition to emphasising the importance of monitoring and maintaining adequate serum levels of vitamin D, in order to reduce possible cognitive sequelae. Results will be announced at national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42018100074.

The effects of vitamin D deficiency on mandibular bone structure: a retrospective radiological study.

OBJECTIVE: The aim of the study was to evaluate the effects of vitamin D deficiency on the mandibular bone structure by fractal analysis and panoramic morphometric indices. METHODS: Ninety participants were divided into three groups as 30 individuals with severe vitamin D deficiency, 30 individuals with vitamin D deficiency, and 30 individuals with vitamin D sufficiency. Fractal dimension analysis (FD), panoramic mandibular index (PMI), mandibular cortical index (MCI), and mandibular cortical thickness measurement (CTM) were evaluated on panoramic radiographs. RESULTS: FD values of the patients with vitamin D deficiency were found to be statistically lower than the patients with vitamin D sufficiency (p < 0.05). FD value of supracortical area above the angulus mandible (FD2) in patients with severe vitamin D deficiency was significantly lower than FD values (p = 0.002). There was no statistically significant difference between the groups in the CTM (p > 0.05). PMI was significantly lower in patients with severe vitamin D deficiency (p < 0.001). There was a significant difference in MCI values between the groups (p < 0.05). CONCLUSION: Vitamin D deficiency causes a decrease in bone mineral density in the mandible, and an increase in alveolar porosity. FD analysis and radiomorphometric indices in panoramic radiographs can be used to assess osteoporotic changes in patients with vitamin D deficiency.

Vitamin D deficit is associated with accelerated brain aging in the general population.

Vitamin D deficiency has been associated with reduced neurocognitive functioning and the neurodegenerative processes. However, existing evidence on brain structural correlates of vitamin D deficiency is controversial. We sought to investigate associations of vitamin D levels with imaging patterns of brain aging. In addition, we investigated whether low vitamin D levels were associated with gray matter volumes, whole brain volumes and hippocampus volumes. Structural MRI data and vitamin D levels were obtained in 1,865 subjects from the general population. Linear regressions were applied to investigate the association of vitamin D levels and vitamin D deficiency with imaging derived brain age, total brain, gray matter and hippocampal volumes. Different sets of covariates were included. Vitamin D deficiency was significantly associated with increased brain age. Also, linear vitamin D levels were significantly associated with total brain and gray matter volumes, while no significant association with hippocampal volume was found. Further interaction analyses showed that this association was only significant for male subjects. Our results support previous findings suggesting that vitamin D-deficient individuals have an accelerated brain aging. In addition, associations between vitamin D levels and total brain/ gray matter volumes suggest neuroprotective effects of vitamin D on the brain.

Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients.

BACKGROUND: Several immune mechanisms activate in COVID-19 pathogenesis. Usually, coronavirus infection is characterized by dysregulated host immune responses, interleukine-6 increase, hyper-activation of cytotoxic CD8 T lymphocytes. Interestingly, Vitamin D deficiency has been often associated with altered immune responses and infections. In the present study, we evaluated Vitamin D plasma levels in patients affected with different lung involvement during COVID-19 infection. METHODS: Lymphocyte phenotypes were assessed by flow cytometry. Thoracic CT scan involvement was obtained by an image analysis program. RESULTS: Vitamin D levels were deficient in (80%) of patients, insufficient in (6.5%) and normal in (13.5%). Patients with very low Vitamin D plasma levels had more elevated D-Dimer values, a more elevated B lymphocyte cell count, a reduction of CD8 + T lymphocytes with a low CD4/CD8 ratio, more compromised clinical findings (measured by LIPI and SOFA scores) and thoracic CT scan involvement. CONCLUSIONS: Vitamin D deficiency is associated with compromised inflammatory responses and higher pulmonary involvement in COVID-19 affected patients. Vitamin D assessment, during COVID-19 infection, could be a useful analysis for possible therapeutic interventions. TRIAL REGISTRATION: 'retrospectively registered'.

Vitamin D and Lung Outcomes in Elderly COVID-19 Patients.

Background and aim: Vitamin D deficiency is frequently reported in patients with SARS-CoV-2 infection. The aim of this study was to correlate the 25OH-Vitamin D serum concentrations with clinical parameters of lung involvement, in elderly patients hospitalized for SARS-CoV-2 infection. Methods: Sixty-five consecutive COVID-19 patients (mean age 76 ± 13 years) and sixty-five sex- and age-matched control subjects (CNT) were analyzed. The following clinical parameters, including comorbidities, were collected at admission: type of pulmonary involvement, respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein). Results: Significantly lower vitamin D serum levels were found in COVID-19 patients than in CNT (median 7.9 vs 16.3 ng/mL, p = 0.001). Interestingly, a statistically significant positive correlation was observed between vitamin D serum levels and PaO2 (p = 0.03), SO2 (p = 0.05), PaO2/FiO2 (p = 0.02), while a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p = 0.04), C-reactive protein (p = 0.04) and percentage of O2 in a venturi mask (p = 0.04). A negative correlation was also observed between vitamin D serum levels and severity of radiologic pulmonary involvement, evaluated by computed tomography: in particular, vitamin D was found significantly lower in COVID-19 patients with either multiple lung consolidations (p = 0.0001) or diffuse/severe interstitial lung involvement than in those with mild involvement (p = 0.05). Finally, significantly lower vitamin D serum levels were found in the elderly COVID-19 patients who died during hospitalization, compared to those who survived (median 3.0 vs 8.4 ng/mL, p = 0.046). Conclusions: This study confirms that 25OH-vitamin D serum deficiency is associated with more severe lung involvement, longer disease duration and risk of death, in elderly COVID-19 patients. The detection of low vitamin D levels also in younger COVID-19 patients with less comorbidities further suggests vitamin D deficiency as crucial risk factor at any age.

Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?

OBJECTIVE: We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week's post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT). METHODS: Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6th and 12th week on the fractured side. RESULTS: 39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss. CONCLUSION: Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.

The effect of maternal vitamin D levels on placental shear wave elastography findings in the first trimester.

The aim of this study was to investigate the effect of maternal serum Vitamin D levels on the elasticity of placenta. Seventy-four spontaneously conceived singleton pregnancies in their first trimester were enrolled into this study. Fifty-one of them had Vitamin D deficiency (<20 ng/mL), while 23 pregnancies had Vitamin D levels ≥20 ng/mL. The placental elasticity was measured by the transabdominal Point Shear Wave Elastography (pSWE) method. In each case, the mean of 10 consecutive measurements was accepted as the mean placental elasticity value. The mean pSWE values did not significantly differ between the Vitamin D deficient group and the control group (p > .05). Placental elasticity was not found to be different in the pregnancies with Vitamin D deficiency during the first trimester.IMPACT STATEMENTWhat is already known on this subject? The pSWE technique provides opportunity to determine the elasticity of any interested tissue. Placental elasticity has been found to be changed in inflammatory and fibrotic conditions such as in preeclampsia, intrauterine growth restriction or diabetes. On the other hand, Vitamin D deficiency is linked with several comorbidities such as autoimmune disorders, cancer and cardiovascular disorders. Vitamin D also plays a role in placental angiogenesis in the first trimester. Maternal Vitamin D levels are shown to be related with adverse pregnancy outcomes.What do the results of this study add? To the best of our knowledge, this study is the first assessing the association between Vitamin D levels and placental elasticity. Placental elasticity was not found to be changed by Vitamin D deficiency.What are the implications of these findings for clinical practice and/or further research? Our pilot study revealed that Vitamin D deficiency does not have any impact on placental elasticity in the first trimester. However, longitudinal studies concerning placental elasticity in subsequent trimesters are needed to support our findings.

Clinical features and the role of magnetic resonance imaging in pediatric patients with intracranial hypertension.

Increased intracranial hypertension (IIH) is a defined clinical condition; however, an unsolved pathophysiologic background usually creates problems in its diagnosis and proper approach. The aim of this study was to emphasize the clinical conditions and brain magnetic resonce imaging (MRI) clues of pediatric patients, especially this clinical entity with high morbidity. Here, we review the etiology, clinical presentation, brain MRI findings, and prognosis of IIH in children. The symptoms' onset age ranged from 9 months to 16 years. Headache (81%), vomiting (37%), and diplopia (33.3%) were the most frequent symptoms. The most common etiologic factors were found to be obesity and dural venous sinus thrombosis. Cerebrospinal fluid (CSF) opening pressure had mean a mean value of 615.2 ± 248 mm H2O. A significant relationship was found between visual field impairment and height of CSF pressure (p < 0.001). Optic nerve sheath enlargement (88.8%) and optic nerve tortuosity (85.1%) were found as the most common brain MRI findings. Slit-like ventricle (37%), venous sinus thrombosis (29.6%), posterior globe sclera flattening (29.6%), empty sella (25.9%), and intraocular protrusion of the optic nerve (14.8%) were the other findings. A significant relationship was found between CSF opening pressure and the presence of optic nerve tortuosity (p = 0.002), and distension of the optic nerve sheath (p = 0.006). All patients received acetazolamide, only one patient underwent lumboperitoneal shunt, and only one received steroids. In children, IIH can present with different etiologies and symptoms. Brain MRI provides crucial clues in diagnosis. Urgent diagnosis and treatment planning are required to protect vision functions.

Associations of vitamin D deficiency with MRI markers of brain health in a community sample.

BACKGROUND & AIM: Vitamin D deficiency has been linked to an increased risk of dementia. To strengthen this evidence and establish whether vitamin D can indeed play a role in early prevention of neurodegeneration, knowledge on underlying pathways is crucial. Therefore, we aimed to investigate the association of vitamin D status with brain tissue volumes, hippocampus volume, white matter integrity, and markers of cerebral small vessel disease (CSVD) in a dementia-free population. METHODS: In this cross-sectional analysis, 2,716 participants free of dementia from the population-based Rotterdam Study underwent serum 25(OH)D concentration assessment and brain magnetic resonance imaging (MRI) scanning between 2006 and 2009. Outcomes of interest included brain tissue volume (total, white matter, grey matter and hippocampus volume), white matter integrity (fractional anisotropy (FA) and mean diffusivity (MD)), and markers of CSVD (white matter hyper intensity (WMH) volume, presence of lacunes and microbleeds). Associations between vitamin D status, both in categories and continuous, and these brain measurements were assessed using multivariable linear and logistic regression models, adjusting for lifestyle and other disease risk factors. RESULTS: We observed that vitamin D deficiency (25(OH)D < 30 nmol/L) was independently associated with smaller brain tissue volume, smaller white matter volume and smaller hippocampus volume as compared to a sufficient vitamin D status (≥50 nmol/L). Vitamin D per 10 nmol/L increment and an insufficient (30-50 nmol/L) as compared to sufficient vitamin D status were not associated with the brain measures of interest. Moreover, vitamin D status was not associated with grey matter volume, white matter integrity or CSVD markers. CONCLUSIONS: In this dementia-free population, vitamin D deficiency was associated with a smaller brain tissue volume and hippocampus volume. More research, in particular with a longitudinal design, is needed to further elucidate the role of vitamin D in neurodegeneration.

Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm.

BACKGROUND: Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology. OBJECTIVE: To explore the vitamin D system as a potential treatment for CVS. METHODS: 25-vitamin D3 levels tested between 2007 and 2015 and data of SAH patients admitted during the months with a peak vs nadir of VitD3 values were analyzed, retrospectively. We prospectively correlated VitD3 and vasospasm/outcome data in SAH patients admitted in 2017. An experimental mice SAH model and cell culture model were used to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25-VitD3). Additionally, the mediators acting in the VitD mechanism were researched and detected. RESULTS: Based on the retrospective analysis demonstrating an increased frequency of vasospasm in SAH patients during the low vitamin D period in winter, we started basic research experiments. Active 1,25-VitD3 hormone attenuated CVS, neurological deficit, and inflammation after intrathecal blood injection in mice. Deletion of the vitamin D receptor in the endothelium or in myeloid cells decreased the protective 1,25-VitD3 effect. Co-culture experiments of myeloid and endothelial cells with blood confirmed the anti-inflammatory 1,25-VitD3 effect but also revealed an induction of stroma-cell-derived factor 1α (SDF1α), vascular endothelial growth factor, and endothelial nitric oxide synthase by 1,25-VitD3. In mice, SDF1α mimicked the protective effect of 1,25-VitD3 against CVS. From bench to bedside, CVS severity was inversely correlated with vitamin D plasma level, prospectively. Patients with more severe CVS exhibited attenuated expression of SDF1α and 1,25-VitD3-responsive genes on circulating myeloid cells. CONCLUSION: 1,25-VitD3 attenuates CVS after SAH by inducing SDF1α. However, VitD administration should be tested as optional treatment to prevent CVS.

Relationship of oxidative stress to visceral adiposity in youth and role played by vitamin D.

BACKGROUND: Visceral adipose tissue (VAT) accumulation is a major cardiometabolic risk factor, associated with increased inflammation. Oxidative stress (OS) is also associated with inflammation and cardiometabolic issues, yet mainly through general obesity. Both OS and obesity were linked to vitamin D deficiency. OBJECTIVES: To investigate whether OS increase is associated with VAT accumulation in youth, and whether in the presence of VAT accumulation, a higher vitamin D status is associated with lower OS. METHODS: One hundred and fifty-eight youth with overweight/obesity, 7 to 17 years old, were recruited (Pediatric Clinic, Luxembourg). We assessed visceral and subcutaneous abdominal adipose tissues by magnetic resonance imaging, OS by DNA/RNA oxidative damage with ELISA and vitamin D by high-performance liquid chromatography. RESULTS: VAT was the body fat compartment the most strongly associated with OS (RPearson : 0.298; P < 10-4 ). The general linear (GLM) models assessing the relationship between OS, VAT and vitamin D concentrations showed that "Log10 OS = (0.003 × VAT) + 3.911 (R2adjusted : 0.083; P-value < 10-4 )"; "Log10 OS = (0.003 × VAT) - (0.156 × log10 vitamin D) + 4.110 (R2adjusted : 0.101; P-value < 10-4 )". After back-transformation of the log-values into normal values, the GLM showed that, for a person with an average value of VAT (40.7 cm2 ), a 10 cm2 increase in VAT would increase OS by approx. 771.833 pg/mL, after age, gender, Tanner stage and physical activity adjustment. An approximate increase of 9 ng/mL of vitamin D would counterbalance this negative effect of increased VAT. CONCLUSION: Dietary strategies improving vitamin D status should be investigated to tackle VAT and OS increase.

Combined Effect of Maternal Vitamin D Deficiency and Gestational Diabetes Mellitus on Trajectories of Ultrasound-Measured Fetal Growth: A Birth Cohort Study in Beijing, China.

OBJECTIVE: Few studies have examined whether maternal 25(OH)D deficiency and gestational diabetes mellitus (GDM) jointly affect fetal growth. We aimed to examine the separate and combined effects of maternal 25(OH)D deficiency and GDM on trajectories of fetal growth. METHODS: We established a birth cohort (2016-2017) with 10,913 singleton pregnancies in Tongzhou Maternal and Child Health Hospital of Beijing, China. Maternal 25(OH)D deficiency (serum 25(OH)D concentration < 20.0 ng/mL) was detected, and GDM was diagnosed at 24~28 gestational weeks. Fetal growth was assessed by longitudinal ultrasound measurements of estimated fetal weight (EFW) and abdominal circumference (AC) from 28 gestational weeks to delivery, both of which were standardized as gestational-age-adjusted Z-score. A k-means algorithm was used to cluster the longitudinal measurements (trajectories) of fetal growth. Logistic regression models were used for estimating exposure-outcome associations and additive interactions. RESULTS: We identified two distinct trajectories of fetal growth, and the faster one resembling the 90th centile curve in the reference population was classified as excessive fetal growth. Maternal 25(OH)D deficiency and GDM were independently associated with an increased risk of excessive fetal growth. The combination of maternal 25(OH)D deficiency and GDM was associated with an increased risk of excessive fetal growth assessed by EFW Z-score (odds ratio (OR): 1.36; 95% confidence interval (CI): 1.15~1.62) and AC Z-score (OR (95% CI): 1.32 (1.11~1.56)), but the relative excess risks attributable to interaction were nonsignificant (P > 0.05). CONCLUSION: Maternal 25(OH)D deficiency and GDM may jointly increase the risk of excessive fetal growth. Interventions for pregnancies with GDM may be more beneficial for those with 25(OH)D deficiency than those without regarding risk of excessive fetal growth, if confirmed in a large sample.

Rachitic change and vitamin D status in young children with fractures.

OBJECTIVE: To examine the association between rachitic changes and vitamin D levels in children less than 2 years old with fractures. METHODS: Children less than 2 years old who were admitted to a large children's hospital for a fracture and underwent a skeletal survey were included. Two pediatric radiologists blinded to the children's vitamin D levels independently reviewed the skeletal surveys for the following rachitic findings: demineralization, widened sutures, rachitic rosary, Looser zones, and metaphyseal changes. Kappa coefficients were calculated to assess inter-rater agreement. Logistic regression was used to test the association between vitamin D level and rachitic findings. RESULTS: There were 79 subjects (40 female and 39 male) with a median age of 4 months. Vitamin D levels ranged from 11.6 to 88.9 ng/ml and were low in 27. Questionable demineralization was noted in seven subjects; mild to moderate demineralization was observed in four subjects. Widened sutures were noted in seven subjects, many also with concurrent intracranial hemorrhage. Lower vitamin D levels were associated with increased odds of demineralization after adjusting for age, gender, and prematurity (P < 0.015). An association was not found between the vitamin D level and suture widening (P = 0.07). None of the cases demonstrated Looser zones, rachitic rosary, or metaphyseal changes of rickets. CONCLUSIONS: Infants and toddlers with fractures frequently have suboptimal vitamin D levels, but radiographic evidence of rickets is uncommon in these children.

Serum Vitamin D and Cingulate Cortex Thickness in Older Adults: Quantitative MRI of the Brain.

BACKGROUND: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults. OBJECTIVE: Our objective was to investigate in older adults whether vitamin D insufficiency<50nmol/L was associated with thinner cingulate cortex, a brain area related to cognitive functions influenced by vitamin D. METHODS: Two hundred and fifteen Caucasian older community-dwellers (mean±SD, 72.1±5.5years; 40% female) received a blood test and brain MRI. The thickness of perigenual anterior cingulate cortex, midcingulate cortex and posterior cingulate cortex was measured using FreeSurfer from T1-weighted MR images. Age, gender, education, BMI, mean arterial pressure, comorbidities, use of vitamin D supplements or anti-vascular drugs, MMSE, GDS, IADL, serum calcium and vitamin B9 concentrations, creatinine clearance were used as covariables. RESULTS: Participants with vitamin D insufficiency (n=80) had thinner total cingulate thickness than the others (24.6±1.9mm versus 25.3±1.4mm, P=0.001); a significant difference found for all 3 regions. Vitamin D insufficiency was cross-sectionally associated with a decreased total cingulate thickness (ß=- 0.49, P=0.028). Serum 25OHD concentration correlated positively with the thickness of perigenual anterior (P=0.011), midcingulate (P=0.013) and posterior cingulate cortex (P=0.021). CONCLUSION: Vitamin D insufficiency was associated with thinner cingulate cortex in the studied sample of older adults. These findings provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.

Relationship between 25-Hydroxyvitamin D, bone density, and Parkinson's disease symptoms.

OBJECTIVES: Vitamin D deficiency is widespread in patients with Parkinson's disease (PD). Our aim was to determine whether serum vitamin D levels correlated with bone mineral density (BMD) and non-motor symptoms in patients with PD. MATERIALS & METHODS: A consecutive series of 182 patients with PD and 185 healthy controls were included. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured by immunoassay, while BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Associations between serum vitamin D levels and clinical data were evaluated using partial correlation analysis. RESULTS: Patients with PD had significantly lower serum 25(OH)D levels relative to healthy controls (49.75 ± 14.11 vs 43.40 ± 16.51, P < 0.001). Furthermore, PD patients with lower vitamin D levels had a significantly higher frequency of falls (P = 0.033) and insomnia (P = 0.015). They also had significantly higher scores for the Pittsburgh Sleep Quality Index (PSQI; P = 0.014), depression (P = 0.020), and anxiety (P = 0.009). Finally, patients with PD also had a significantly lower mean BMD of the lumbar spine (P = 0.011) and femoral neck (P < 0.001). After adjusting for age, sex, and body mass index, vitamin D levels significantly correlated with falls, insomnia, and scores for the PSQI, depression, and anxiety. CONCLUSIONS: In patients with PD, vitamin D levels significantly correlated with falls and some non-motor symptoms. However, no associations were found between BMD and the serum 25(OH)D levels in patients with PD. Thus, vitamin D supplementation is a potential therapeutic for non-motor PD symptoms.

Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE).

OBJECTIVE: To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS). METHODS: In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (<75 nmol/L), a treatment with interferon beta-1a 44 µg (SC 3 times per week) 4 months ± 2 months before randomization, and at least one documented relapse during the previous 2 years. Patients received high-dose oral cholecalciferol 100,000 IU or placebo every other week for 96 weeks. Primary outcome measure was the change in the annualized relapse rate (ARR) at 96 weeks. Secondary objectives included safety and tolerability of cholecalciferol and efficacy assessments (ARR, MRI parameters, and Expanded Disability Status Scale [EDSS]). RESULTS: The primary end point was not met. In patients who completed the 2-year follow-up (45 with cholecalciferol and 45 with placebo), all efficacy parameters favored cholecalciferol with an ARR reduction (p = 0.012), less new hypointense T1-weighted lesions (p = 0.025), a lower volume of hypointense T1-weighted lesions (p = 0.031), and a lower progression of EDSS (p = 0.026). The overall rate of adverse events was well balanced between groups. CONCLUSIONS: Although the primary end point was not met, these data suggest a potential treatment effect of cholecalciferol in patients with RRMS already treated with interferon beta-1a and low serum 25OHD concentration. Together with the good safety profile, these data support the exploration of cholecalciferol treatment in such patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01198132. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS and low serum 25OHD, cholecalciferol did not significantly affect ARRs.

Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment.

Vitamin D deficiency may exacerbate adverse neurocognitive outcomes in the progression of diseases such as Parkinson's, Alzheimer's, and other dementias. Mild cognitive impairment (MCI) is prodromal for these neurocognitive disorders and neuroimaging studies suggest that, in the elderly, this cognitive impairment is associated with a reduction in hippocampal volume and white matter structural integrity. To test whether vitamin D is associated with neuroanatomical correlates of MCI, we analyzed an existing structural and diffusion MRI dataset of elderly patients with MCI. Based on serum 25-OHD levels, patients were categorized into serum 25-OHD deficient (<12 ng/mL, n = 27) or not-deficient (>12 ng/mL, n = 29). Freesurfer 6.0 was used to parcellate the whole brain into 164 structures and segment the hippocampal subfields. Whole-brain structural connectomes were generated using probabilistic tractography with MRtrix. The network-based statistic (NBS) was used to identify subnetworks of connections that significantly differed between the groups. We found a significant reduction in total hippocampal volume in the serum 25-OHD deficient group especially in the CA1, molecular layer, dentate gyrus, and fimbria. We observed a connection deficit in 13 regions with the right hippocampus at the center of the disrupted network. Our results demonstrate that low vitamin D is associated with reduced volumes of hippocampal subfields and connection deficits in elderly people with MCI, which may exacerbate neurocognitive outcomes. Longitudinal studies are now required to determine if vitamin D can serve as a biomarker for Alzheimer's disease and if intervention can prevent the progression from MCI to major cognitive disorders.

Vitamin D, bone mineral density and risk of fracture in people with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors. METHOD: We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment. Blood sample were taken for vitamin D and related analytes. dual-energy X-ray absorptiometry for BMD was performed. RESULTS: Of 51 study participants (mean [standard deviation, SD] age 51.5 [13.6] years, 57% male), 41 (80.4%) were taking vitamin D and 10 were not. Mean [SD] serum vitamin D was 81.3 [21.3] vs. 25.2 [10.2] nmol/L (P < 0.0001), respectively. Thirty-six participants underwent a dual-energy X-ray absorptiometry scan, which showed osteoporosis in 23.7% and osteopenia in 52.6%. Participants on vitamin D had higher BMD than those who were not, a statistically significant difference when confounders (lack of mobility and hypogonadism) were removed. BMD was significantly different according to mobility, particularly in wheelchair users, in whom hip BMD was 33% lower (P < 0.0001) than in participants with normal mobility. Participants still taking vitamin D showed a 6.1% increase in BMD at the spine (P = 0.003) after mean [SD] 7.4 [1.5] years vitamin D treatment. CONCLUSIONS: In people with IDs and previous vitamin D deficiency, BMD increases on long-term vitamin D supplementation. However, additional strategies must be considered for osteoporosis and fracture prevention in this population.

The rachitic tooth: The use of radiographs as a screening technique.

This study investigates morphological changes in pulp chambers of living and archaeological individuals with past vitamin D deficiency. Living individuals (n=29), four with detailed medical and dental records and three groups of archaeological individuals (n=25) were radiographed; selected individuals were further evaluated histologically for the presence of incremental interglobular dentin (IIGD), indicative of deficiency (28 living; 17 archaeological). Measurements of pulp horns/chambers from radiographs were conducted to quantify morphological observations. One group had clear skeletal evidence of rickets from St. Matthew, Quebec (n=1) and St. Jacques, France (n=4); a second group had slight skeletal indicators from Bastion des Ursulines, Quebec (n=6); and a third group lacked both skeletal and radiological evidence of deficiency from St. Antoine (n=6) and Pointe-aux-Trembles (n=4). Results showed archaeological individuals with clear and slight skeletal evidence of past deficiency displayed constricted or chair shaped pulp horns. Living individuals with deficiency exhibited similar pulp chamber morphology. Radiographic pulp horn/chamber measurements corroborated morphological findings and significant differences were found in pulp horn/chamber measurements between those with and without deficiency. Results suggest that radiograph assessment of teeth can be used as a screening technique to elucidate patterns of deficiency and select individuals for microCT or histological assessment.