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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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

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., Competing Interests: Declaration of Competing Interests All authors declare no conflicts of interest related to this work., (Copyright © 2022. Published by Elsevier B.V.)

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 H 2 O. 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., (© 2020. Belgian Neurological Society.)

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 STATEMENT What 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.

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'.

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 6 th and 12 th 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., Competing Interests: The authors have no conflict of interest.

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 (PaO 2 , SO 2 , PaCO 2 , PaO 2 /FiO 2 ), 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 PaO 2 ( p = 0.03), SO 2 ( p = 0.05), PaO 2 /FiO 2 ( 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 O 2 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.

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., (© Congress of Neurological Surgeons 2020.)

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., Competing Interests: Conflict of interest All authors have no conflict of interest to disclose regarding the present study., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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 (R Pearson : 0.298; P < 10 -4 ). The general linear (GLM) models assessing the relationship between OS, VAT and vitamin D concentrations showed that "Log 10 OS = (0.003 × VAT) + 3.911 (R 2 adjusted : 0.083; P-value < 10 -4 )"; "Log 10 OS = (0.003 × VAT) - (0.156 × log 10 vitamin D) + 4.110 (R 2 adjusted : 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 cm 2 ), a 10 cm 2 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., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 90 th 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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Zheng Liu et al.)

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.

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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., (© 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

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., (© 2018 Wiley Periodicals, Inc.)

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 (β=- 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Vitamin D deficiency and quantitative ultrasound measurements are associated with bone fragility. We assessed these parameters and their correlates. 87.7% of the population has vitamin D inadequacy and this correlated with lifestyle factors. These results contribute to epidemiological data needed for population guidelines for bone health., Purpose: Vitamin D deficiency and quantitative ultrasound (QUS) parameters are among the most important clinical risk factors of bone fragility. Few data are available for Greek population. The aim of the study was to evaluate the serum 25-hydroxyvitamin D [25(OH)D] level and their determinants, as well as QUS parameters in Greek population., Methods: OSTEOS is an observational cross-sectional study conducted from June 2010 to July 2012. Nine hundred seventy adults were recruited from rural and urban areas throughout Greece and completed the appropriate questionnaire. Serum 25(OH)D measured by enzyme immunoassay, QUS parameters, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), was assessed with an Achilles device. Univariate Analysis of Variance was used for the assessment of serum 25(OH)D determinants., Results: Mean serum 25(OH)D of the total population was 20,00 ± 8,00 ng/mL. Females had lower levels than males. The negative determinants of serum 25(OH)D in the total population were the female sex and the winter-spring season of sampling while age proved negative association solely in obese subjects. Positive determinants of vitamin D status were summer sun exposure and organized physical activity as expected. Urban had lower SOS and SI than rural residents. Individuals with 25(OH)D ≥ 20 ng/mL had higher SOS than those with 25(OH)D < 20 ng/mL. BUA, SOS, and SI are positively correlated with organized physical activity and negatively with PTH., Conclusions: This study reports that vitamin D deficiency is highly prevalent among healthy Greek men and women, demonstrates the multifactorial causation of 25(OH)D levels, and points out that further research is required to determine more factors related to vitamin D status and bone health.

25-Hydroxyvitamin D (25(OH)D) deficiency is a frequent condition in patients who suffer acute ischemic stroke (AIS), and several studies suggested that it may be associated with a poorer prognosis. Whether this association is affected by hypertension is unclear. Our aim was to investigate the association between 25(OH)D levels and both clinical severity and outcome after 3 months in AIS patients stratified by the history of hypertension. Consecutive first-ever AIS patients admitted to the Third Affiliated Hospital of Sun Yat-sen University, China were identified. Clinical information was collected. Serum 25(OH)D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome was evaluated after 3 months of onset using the modified Rankin Scale (mRS). Multivariate analyses were performed using logistic regression models. During the study period, 377 patients were diagnosed as AIS and were included in the analysis. 25(OH)D deficiency was not associated with the risk of NIHSS at admission and 3 months mRS both in total patients and the hypertension subgroup. Among AIS without hypertension, 25(OH)D deficiency subjects had a significantly higher of NIHSS at admission and 3 months mRS compared with those with 25(OH)D ≥ 50 nmol/L. The odds ratios (95% confidence interval) were 5.51(1.83-16.60) and 4.63(1.53-14.05) in the multivariable adjusted model (P for linear trend < 0.05). Serum lower 25(OH)D levels can be seen as an independent prognostic factor of functional outcome in AIS without hypertension. Additional studies about improving prognosis of AIS by vitamin D supplementation could be first applied to these patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Data describing the effect of in vivo B cell depletion on general bone loss in patients with rheumatoid arthritis (RA) are limited. Given the pathogenetic role of B cells in RA, it is tempting to speculate that B cell depletion might have a beneficial effect on bone loss. We prospectively investigated the changes in bone mineral density (BMD), bone turnover, inflammation and disease activity before and after rituximab in 45 RA patients over a 12 month period, 36 patients of whom completed the study and were included in the analysis. There was no significant change in our primary endpoint; lumbar spine BMD after 12 months. However, we found a significant decrease in neck of femur (mean -0.017 g/cm2, 95% CI -0.030, -0.004 p = 0.011) and total femur BMD (mean -0.016 g/cm2, 95% CI -0.025, -0.007 p = 0.001). Additionally, there was a significant increase in procollagen type 1 amino-terminal propeptide (P1NP) and bone specific alkaline phosphatase (BAP); biomarkers of bone formation (median change from baseline to 12 months; P1NP 11.3 μg/L, 95% CI -1.1, 24.8 p = 0.025; BAP 2.5 μg/L, 95% CI 1.2, 3.6 p = 0.002), but no significant change in bone resorption or osteocyte markers. The fall in BMD occurred despite improvement in disease control. Post-menopausal women had the lowest mean lumbar spine, femoral and forearm BMD at baseline and after 12 months, additionally they had a higher level of bone turnover throughout the study. In conclusion, BMD was maintained at the lumbar spine and forearm, but fell at the femur sites. A high prevalence of vitamin D deficiency was observed and these patients had lower BMD and evidence of higher bone turnover., Competing Interests: JMvL has received honoraria from Roche, Eli Lilly, MSD, Pfizer, Arthrogen and BMS, consultancy fees from Janssen, plus funding from Astra Zeneca, MSD and Genentech. GW, ME, KN, SPT and HKD declare that they have no conflict of interest. The company Roche provided funding for the study (no salaries) and also viewed the article prior to sending for review, but did not change it and had no input into the conduction of the study, analysis or writing up. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.

Context: Accurate preoperative localization of abnormal parathyroid tissue aids importantly in minimally invasive parathyroidectomy in patients with primary hyperparathyroidism. Vitamin D deficiency may possibly influence the success and characteristics of pre-operative localization because it is associated with more active disease and possibly larger adenomas. This could increase the sensitivity of the sestamibi to identify abnormal parathyroid tissue, but earlier reports are conflicting. Vitamin D deficiency could also influence the nature of preoperative localization because it could lead to multi-gland stimulation of parathyroid tissue giving an appearance of multi-gland disease, which may lower accuracy of preoperative localization with sestamibi., Objective: To examine the relationship between vitamin D deficiency and correct parathyroid tissue localization by four-pole thyroid quadrant analysis., Design: Retrospective study., Setting: Referral center., Participants: A total of 138 patients were divided into three groups according to the level of 25OHD; <20 ng/mL (vitamin D deficient), ≥20 to <30 ng/mL (vitamin D insufficient) and ≥30 ng/mL (vitamin D replete)., Main Outcomes: Quadrant localization using 99m Tc-sestamibi/SPECT., Results: Among those with single-gland disease, the proportion of patients with correct quadrant localization were 60.0, 68.3 and 63.5% (p = 0.778), and the accuracy of sestamibi was 89.3, 90.6 and 89.9% for the deficient, insufficiency and replete groups, respectively. Among those with multi-gland disease, the proportion of patients with correct quadrant localization were 50.0, 25.0 and 18.2% (p = 0.619) while the accuracy was 50.0, 50.0 and 45.5%, respectively. Multi-gland disease did not occur more frequently in any of the three groups (p = 0.296)., Conclusions: Vitamin D levels do not affect the accuracy of preoperative localization with sestamibi.

We present the case of a 32-year-old male patient complaining of recurrent mandibular pain for 3.5 years. Panoramic radiography indicated increased cortical density of the mandibular lower border. Scintigraphy and single-photon emission computed tomography revealed metabolic hyperactivity in that region without pathologic lymph nodes. A bone biopsy specimen of the mandibular lower border did not have inflammation or cytologic atypia. Endocrinologic investigation confirmed secondary hyperparathyroidism as a result of hypovitaminosis D. Several weeks after starting therapy with oral vitamin D supplements, the symptoms completely disappeared. Increased cortical density is a rare manifestation of secondary hyperparathyroidism, which normally causes the lamina dura to vanish and produces a ground-glass appearance as a result of blurring of the trabecular bone pattern. Because focal hyperostosis can have multiple benign or malignant causes, radiologic examination of the jaw bones is indispensable for evaluating orofacial pain. Increased cortical density may be caused by metabolic diseases, requiring further investigations, including biopsy and blood analysis., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study is to investigate whether 25-hydroxyvitamin D [25(OH) D] is associated with initial stroke severity and infarct volume, using diffusion-weighted imaging (DWI) in patients with acute ischemic stroke., Methods: We studied a total of 235 patients who were admitted within 24 hours of acute ischemic stroke onset. Initial stroke severity was assessed using the NIH Stroke Scale (NIHSS) score. Infarct volume was measured using DWI. Multivariable linear and logistic regression analyses were used to test whether 25(OH) D represents an independent predictor of infarct volume and stroke severity (NIHSS score of ≥6)., Results: Among 235 study patients, the median age was 64 years (IQR 56-75 years), and 125 (53.2%) were women. In multivariable models adjusted for other significant risk factors, 25(OH) D levels in the lowest and second interquartiles were associated with an increased risk of a NIHSS≥6 (with highest 25 (OH) D quartile as reference) with odd ratios (OR) 3.02(95% confidence interval [CI]:1.59-6.34) and 5.85(2.90-11.54). The median DWI infarct volumes for the serum 25(OH) D level quartiles (lowest to highest) were 12.35, 6.55, 2.44, and 1.59 ml. The median DWI infarct volume in the lowest serum 25(OH) D level quartile was larger than that in the other 3 quartiles (P<0.001). The median adjusted DWI infarct volume in the lowest serum 25(OH) D level quartile was statistically significantly larger than that in the other 3 quartiles (P<0.01)., Conclusion: In conclusion, reduced serum 25(OH) D levels in acute ischemic stroke are an early predictor of larger volumes of ischemic tissue and worse neurological deficit (assessed by the NIHSS)., Competing Interests: The authors report no declarations of interest.

Introduction: Pneumosinus dilatans (PSD) is a rare disorder of undetermined etiology characterized by expansion of the paranasal sinuses without bony erosion. Of the few cases of PSD described in indexed pediatric literature, there has been no reported case of this disorder presenting with optic canal stenosis in the setting of a vitamin deficiency., Case Material: A 12-year-old girl presented with a 3-month history of progressive, painless, and asymmetric visual deterioration in her eyes. MRI showed prominent perioptic CSF spaces bilaterally and mild atrophy of both the optic nerves. CT head showed hyperpneumatization of the sphenoethmoidal air cells and both anterior clinoid processes with the optic nerves contained within narrowed intact bony canals. Blood investigations showed reduced vitamin D levels, and a subsequent skeletal survey showed diffuse osteopenia. She underwent endoscopic sphenoidotomy and bilateral decompression of the optic nerves. Following surgery, she reported improvement of vision in her left eye. She was started on vitamin D supplements for the endocrine abnormality. At a follow-up visit 6 months later, her visual acuity in both her eyes had improved., Conclusion: Pneumosinus dilatans is an unusual cause of progressive optic nerve dysfunction in the pediatric population. In the absence of any associated intracranial pathologies, conditions like hypovitamosis D should be ruled out.

Patients with osteoporosis have a low bone mass resulting in an increased risk for bone fractures, morbidity and mortality. One hundred thirty-one female pre-menopausal participants (98 Turkish immigrants living in Germany in comparison with 33 age-matched healthy Germans) were recruited for this study which explored vitamin D deficiency and specific genetic modifications of bone metabolism. The subjects were investigated for their femoral and lumbar bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) of the right total femur and the lumbar spine. Serum levels of osteologic parameters were determined: parathormone (PTH), calcium (Ca), osteocalcin (OC), phosphate (P), alkaline phosphatase (AP), beta-crossLaps (CL), tartrate-resistant acid phosphatase isoform 5b (TRAP5b), and 25-vitamin D 3 (25-OH D 3 ). The Bsml- and Fokl-polymorphisms of the vitamin D receptor (VDR) gene and the collagen type I alpha 1 (COLIA1)-gene polymorphism were also genotyped. An extremely high prevalence of vitamin D deficiency could be found in the immigrant cohort (87.8 %). Osteoporosis but not osteopenia was more prevalent in this group. Among immigrants with osteoporosis, TRAP5b was elevated in 42.9 % and beta-CL in 28.6 %. Only the Fokl FF-genotype of the VDR polymorphism was significantly more prevalent among the Turkish women, Ff-genotyped immigrants showed significantly decreased BMD. A significant correlation between the COLIA1-gene polymorphism and BMD could not be identified in the two groups. Vitamin D deficiency and osteoporosis appear to be dominant and unrecognized problem among female Turkish immigrants in Germany. Therefore, in this population, osteologic parameters and BMD should be routinely analyzed and deficiencies be treated immediately.

Stress fractures and other bony stress injuries occur along a spectrum of severity which can impact treatment and prognosis. When treating these injuries, it should be borne in mind that no two stress fractures behave exactly alike. Given that they are not a consistent injury, standardized treatment protocols can be challenging to develop. Treatment should be individualized to the patient or athlete, the causative activity, the anatomical site, and the severity of the injury. A holistic approach to the treatment of the most difficult stress fractures should be taken by orthopedists and sports medicine specialists. This approach is necessary to obtain optimal outcomes, minimize loss of fitness and time away from sports participation, and decrease the risk of recurrence.

Diabetes is an established risk factor for erectile dysfunction (ED). The pathophysiology of ED in diabetic men is multifactorial, but it mainly involves a vascular disorder related to a reduction of endothelial function. Recently, several studies have correlated ED risk factors with vitamin D deficiency. In this study, we evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] levels, erectile dysfunction, and vascular disease, in type 2 diabetes mellitus men (T2DM). In this observational study, 92 T2DM males (58.83 ± 9.73 years) underwent medical history collection, International Index of Erectile Function (IIEF-5) questionnaire, that allows the identification and grading of DE, physical examination, biochemical/hormonal blood tests, and penile echo-color Doppler ultrasonography. T2DM patients with lower 25(OH)D levels (<25 nmol/l) showed higher penile IMT (p < 0.05), waist circonference (p < 0.05), glucose concentrations (p < 0.05), and lower IIEF-5 score (p < 0.005), testosterone concentrations (p < 0.05), and cavernous peak systolic velocity (PSV) (p < 0.05), compared to patients with 25(OH)D >50 nmol/l. 25(OH)D levels were directly correlated with IIEF-5 (R = 0.39; p = 0.0001), testosterone (R = 0.24; p = 0.02), and PSV (R = 0.24; p = 0.04) and inversely with waist (R = -0.33; p = 0.002), HbA1c (R = -0.22; p = 0.03), triglyceride (R = -0.21; p = 0.06), and penile IMT (R = -0.30; p = 0.009). At multivariate analysis, 25(OH)D deficiency remained an independent predictor of DE. We demonstrate a significant association between 25(OH)D deficiency and erectile dysfunction in T2DM men. This association may be due to the influence of 25(OH)D deficiency on cardiovascular risk factor (glycaemia, HDL cholesterol, and triglycerides), testosterone plasma levels and endothelial dysfunction.

Unlabelled: Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents., Introduction: The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents., Methods: Three hundred thirty-three girls and 230 boys (12-16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed., Results: Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D < 25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels., Conclusion: Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

There is currently insufficient information on serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and bone mineral status in healthy adolescents to allow reference values to be set. This study aimed to provide comparable data on vitamin D status in Japanese adolescents and to assess sex differences in susceptibility to vitamin D insufficiency. Serum 25OHD and PTH concentrations were measured in 1,380 healthy adolescents (aged 12-18 years). Subjects completed a questionnaire on exercise history, diet, and lifestyle factors. Calcaneal stiffness was evaluated by quantitative ultrasound. Serum 25OHD concentrations in boys and girls were 60.8 ± 18.3 and 52.8 ± 17.0 nmol/L, respectively. Approximately 30 % of boys and 47 % of girls had suboptimal 25OHD concentrations (<50 nmol/L). Serum PTH concentration was negatively correlated with serum 25OHD concentration in boys, but negatively correlated with calcium intake rather than serum 25OHD in girls. In contrast, the increment in calcaneal stiffness as a result of elevation of serum 25OHD was higher in girls than in boys. As vitamin D deficiency is common in Japanese adolescents, it was estimated that intakes of ≥12 and ≥14 μg/day vitamin D would be required to reach 25OHD concentrations of 50 nmol/L in boys and girls, respectively. Moreover, the results of the present study indicate that vitamin D deficiency has a greater association with calcaneal stiffness in girls than in boys.

Vitamin D deficiency is common among African Americans in the United States and is associated with increased cardiovascular disease risk. In this study, prediabetic African American males who were found to be vitamin D-deficient were randomized to vitamin D supplementation and assessed for changes in left atrial (LA) volume. Prediabetic African American males who were vitamin D-deficient (25(OH)D: 5.0-29 ng/mL) were randomized to high-dose ergocalciferol or placebo. Echocardiography was performed at baseline and at 1 year. Ejection fraction (EF), septal and posterior wall thickness, LA area, LA length, LA volume, E, A, septal and lateral e' and a', deceleration time, and isovolumetric relaxation time were collected. Eighty-one of 158 (51%) subjects received vitamin D2 . Baseline characteristics were similar among both groups. In the placebo group, left atrial volume significantly increased on follow-up (LA volume increased 6.3 mL, P = 0.0025). Compared with placebo group, the treatment group with ergocalciferol had attenuated increases in left atrial volume (LA volume increased 2.6 mL, P = 0.29). Changes in left atrial volume persisted when indexed to body surface area. There was no significant difference in other diastolic parameters and blood pressure between groups. In conclusion, vitamin D-deficient prediabetic African American males who were treated with high-dose vitamin D2 were found to have attenuated increases in left atrial volume compared with controls over 12-month follow-up., (© 2015, Wiley Periodicals, Inc.)

Objective: We evaluated the utility of the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency., Methods: This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the WHO FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures., Results: We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between -1 and -2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant., Conclusion: We found a high prevalence of subclinical vertebral fractures among vitamin D-deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population.

Objectives: To evaluate the bone health and vitamin D levels of a cohort of patients with relapses of multiple sclerosis (MS) and to propose an algorithm for the management of bone health in this patient group., Methods: We prospectively studied 56 consecutive patients from our acute relapse clinic. 3 patients were excluded from analysis as they were not deemed to have experienced an acute MS relapse. Bone health was assessed with vitamin D levels and Dual Energy X-ray Absorptiometry (DEXA) scanning (10 patients failed to attend for DEXA). Statistical analyses were used to compare groups and identify predictive variables. A review of the literature led to a proposed management protocol., Results: Pre-relapse the baseline EDSS was ≤6.5 in all subjects, and <4.0 in the majority (66%). Most received corticosteroids. 51% had low bone mineral density (BMD) as defined by a T-score less than -1.0 on DEXA scanning. Three were osteoporotic (T-score less than -2.5). Thirty one of fifty (62%) subjects were Vitamin D deficient (25(OH)D less than 50nmol/L). A range of variables, including previous corticosteroid usage, were not significantly predictive of reduced BMD., Conclusions: There was a high frequency of both low BMD and Vitamin D deficiency in this cohort of relatively young and largely ambulatory patients experiencing MS relapses. Current tools, such as the WHO FRAX algorithm, are inadequate in assessing bone status and fracture risk in this patient group, predominantly as they are focused on older age groups. We propose a simple clinical management algorithm., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background and Objectives: Gastrointestinal dysfunction is a common non motor symptom in Parkinson's disease (PD). However, the potential association between vitamin D and gastroparesis in PD has not been previously investigated. The aim of this study was to compare vitamin D levels between drug-naive de novo PD patients with normal gastric emptying and those with delayed gastric emptying., Methods: Fifty-one patients with drug-naive de novo PD and 20 age-matched healthy controls were enrolled in this study. Gastric emptying time (GET) was assessed by scintigraphy, and gastric emptying half-time (T1/2) was determined. The PD patients were divided into a delayed-GET group and a normal-GET group., Results: The serum 25-hydroxyvitamin D3 levels were decreased in the delayed-GET group compared with the normal-GET and control groups (11.59 ± 4.90 vs. 19.43 ± 6.91 and 32.69 ± 4.93, respectively, p < 0.01). In the multivariate model, the serum 25-hydroxyvitamin D3 level was independently associated with delayed gastric emptying in PD patients., Conclusions: Vitamin D status may be an independent factor for gastric dysmotility in PD. Although the underlying mechanism remains to be characterized, vitamin D status may play a role in the pathogenesis of delayed gastric emptying in drug-naive PD., (© 2016 S. Karger AG, Basel.)

There is evidence of a role of vitamin D in cognitive functioning, but little is known about the type of functions involved. To describe vitamin D status in a population of old patients with memory complaints and its relationships with cognitive performance and white matter lesions. A retrospective single-centre observational study from the medical records of 244 patients who had a measurement of serum 25OHD together with a battery of neuropsychological tests during a complete geriatric and memory assessment in a day care hospital. The results of the 10 neuropsychological tests considered in this study were analysed as binary variables, opposing patients with results within the highest two tertiles to patients with the worse results or unable to perform the test. Mean age of people included was 80.2 ± 8.1 years and 64% of patients were women. Severe deficiency in vitamin D (25OHD <10 ng/mL) was found in 34 patients (13.9%) and moderate deficiency (10 ≤ 25OHD < 30 ng/mL) in 148 (60.7%). Compared to subjects with sufficient concentrations in vitamin D, patients with severe deficiency performed significantly worse on a global test, the Mini mental state examination, and two tests of verbal memory, the 5 words and the 16-item free and cued recall, independently from age, gender, education, body mass index and autonomy (OR = 2.85 [1.04-7.85], 4.31 [1.42-13.07], and 3.04 [1.01-9.19] respectively). Levels of vitamin D did not differ according to the extent of white matter lesions, visualized semi-quantitatively on magnetic resonance imaging of 115 subjects. This study confirms the high prevalence of vitamin D deficiency in elderly population and suggests a link between vitamin D deficiency and memory.

Oral retinoids are being increasingly used to treat ichthyotic disorders in children. We report on two children with ichthyotic disorders who developed unusual manifestations after they were started on oral retinoids. The first case is a 10-year-old girl with nonbullous ichthyosiform erythroderma and the second is a 2-year-old girl with lamellar ichthyosis. The child with ichthyosiform erythroderma developed features of rickets within months of initiation of systemic retinoids. Her baseline examination before initiation of oral retinoids was normal. The second patient with lamellar ichthyosis was found to have low vitamin D levels after 6 months of retinoid therapy, and prompt supplementation reversed the levels in 2 months. These cases are being reported to bring attention to the probable need for initiation of vitamin D supplementation with systemic retinoid therapy in ichthyotic disorders in children., (© 2015 Wiley Periodicals, Inc.)

Objective: Subclinical hypothyroidism and vitamin D deficiency are common. The diastolic function of patients with both subclinical hypothyroidism and vitamin D deficiency remains unknown. This study aimed to investigate diastolic dysfunction in patients with both subclinical hypothyroidism and vitamin D deficiency., Subjects and Methods: This study included 254 patients. All patients underwent standard Doppler echocardiography. Patients who had risk factors for diastolic dysfunction or had used L-thyroxine and vitamin D within the previous 3 months were excluded. Vitamin D deficiency was defined as a 25-OH-vitamin D level lower than 20 ng/ml, and vitamin D sufficiency was defined as a 25-OH-vitamin D level ≥ 30 ng/ml. Subclinical hypothyroidism was defined as a TSH level of 4.5-10 mU/l when the free T4 concentration was normal., Results: The patients were divided into 4 groups. Group 1 (n=71) included patients with subclinical hypothyroidism and vitamin D deficiency; Group 2 (n=66) included patients with subclinical hypothyroidism and vitamin D sufficiency; Group 3 (n=65) included euthyroid patients with vitamin D deficiency; and Group 4 (n=52) included euthyroid patients with vitamin D sufficiency. LAVI (31.3 ± 3.2, 28.7 ± 3.0, 28.4 ± 3.4, and 27.9 ± 3.9; p<0.001) and E/E' values (11.2 ± 2.7, 8.9 ± 2.7, 9.1 ± 2.9, 8.8 ± 2.5; p<0.001) were significantly higher in Group 1 than in Groups 2, 3 and 4. E' values were significantly lower in Group 1 than in Groups 2, 3 and 4., Conclusion: The coexistence of subclinical hypothyroidism with vitamin D deficiency can lead to further deterioration in the LV diastolic function via the regulation of intracellular calcium and induction of inflammatory activity. Therefore, close follow-up of the diastolic functions of these patients could be beneficial.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease with high prevalence of osteoporosis. Previous evidence indicates an association between vitamin D deficiency and autoimmune diseases. The aim of this study was to evaluate serum 25 hydroxyvitamin D [25(OH)D] levels, bone mineral density (BMD) and disease activity in RA patients living in Argentina. We studied 34 RA women and 41 healthy women as a control group. RA patients had lower 25(OH)D levels (20.4 ± 0.9 ng/ml) than controls (26.3 ± 1.9 ng/ml; p < 0.05). No significant differences were found in lumbar spine BMD between premenopausal (preM) or postmenopausal (postM) patients, but femoral neck BMD was significantly lower in postM RA patients (T score -2.5 ± 0.4) than in postM control subjects (T score -0.9 ± 0.3, p = 0.014). Although no linear correlation between 25(OH)D levels and disease activity (DAS-28) was found, patients with moderate-high disease activity had lower 25(OH)D levels than those with low disease activity: DAS-28 >3.2: 19.5 ± 0.88 ng/ml; DAS-28 ≤3.2: 23.7 ± 2.8 ng/ml (p = 0.047). After 1 year of vitamin D treatment 25(OH)D levels were increased while DAS-28 were decreased (n = 25; p < 0.05). We conclude that patients with RA had lower 25(OH)D levels than the control group. Low levels of 25(OH)D were associated with moderate-high disease activity suggesting the importance of optimal 25(OH)D levels in RA patients. Femoral neck BMD was lower in postM RA patients. No differences in lumbar BMD were found between preM and postM RA patients, suggesting that bone mass evaluation in RA patients should include femoral neck BMD regardless of age.

This study aims to investigate the association between vitamin D levels and distal femoral cartilage thickness in healthy subjects. Eighty patients who were admitted to our outpatient clinic between May and July 2013 were classified into three subgroups according to their 25-OH vitamin D levels of <10, 10-20, and ≥20 ng/mL. Distal femoral cartilage thickness was measured from the midpoints of the right medial condyle (RMC), right lateral condyle (RLC), right intercondylar area (RIA), left medial condyle (LMC), left lateral condyle (LLC), and left intercondylar area (LIA) by using musculoskeletal ultrasound (US). The group with severe vitamin D deficiency (<10 ng/mL) had thinner femoral cartilage thickness at LMC (p = 0.005). Positive correlations were determined only between vitamin D levels and US measurements in the severe vitamin D deficiency group at RLC (r = 444, p = 0.020), LMC (r = 357, p = 0.067), and LLC (r = 568, p = 0.002). Low levels of vitamin D seem to affect the femoral cartilage thickness, adversely. Further studies are necessary to ascertain the clinical relevance of this change in cartilage thickness and whether vitamin D supplementation can reverse the cartilage thinning process or the allied clinical symptoms in the course of knee osteoarthritis.

Objective: Deficiency of 25-hydroxyvitamin D [25(OH)D] is reported to be common in patients with rheumatoid arthritis (RA); data in patients with juvenile idiopathic arthritis (JIA) are inconsistent. We assessed serum 25(OH)D in children, adolescents and young adults with JIA, in order to identify the risk factors for vitamin D deficiency in patients with JIA., Methods: We evaluated 152 patients with JIA: 115 female, 37 male, mean age 16.2 ± 7.4 yrs; evaluated by onset type, 96 had oligoarticular, 35 polyarticular, 7 systemic, and 14 enthesitis-related arthritis (ERA). Patients were compared with a control group matched for sex and age. All patients and controls underwent laboratory tests of plasma 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, and bone alkaline phosphatase levels, and dual-energy x-ray absorptiometry examination., Results: Patients with JIA showed significantly reduced 25(OH)D levels compared to controls (p < 0.001), even divided into subtypes (oligoarticular, p < 0.05; polyarticular, p < 0.005; systemic, p < 0.001; ERA, p < 0.005). Patients with active disease and/or frequent relapses had significantly reduced 25(OH)D levels compared to patients with no active disease and no frequent flares (p < 0.005, respectively). Nevertheless, JIA patients had significantly higher PTH levels compared to controls (p < 0.0001). JIA patients with 25(OH)D deficiency showed a significantly lower bone mineral apparent density than those with normal 25(OH)D levels (p < 0.001)., Conclusion: JIA patients have reduced 25(OH)D and higher PTH values. This may explain at least in part why JIA patients, despite more effective current drugs, do not achieve bone-normal condition over time. JIA patients with more severe disease could require higher supplementation of vitamin D to maintain normal 25(OH)D serum levels. Longterm studies are needed to investigate the relationship between serum 25(OH)D levels and disease activity in JIA.

Context: Vitamin D (25OHD) deficiency may be a modifiable cardiovascular (CV) risk factor. 25OHD insufficiency (20-29 ng/mL) and deficiency (<20 ng/mL) are common in primary hyperparathyroidism (PHPT), but their association with CV disease in PHPT has not been systematically investigated., Objective: This study evaluated whether low 25OHD is associated with subclinical CV disease in PHPT., Design: This is a cross-sectional analysis of PHPT patients with and without low 25OHD., Settings and Participants: We studied 110 PHPT patients in a university hospital setting., Outcome Measures: We measured carotid intima-media thickness; carotid plaque presence/thickness; carotid strain and stiffness; left ventricular mass index; cardiac systolic and diastolic function; and mitral annular calcification., Results: Low 25OHD levels (<30 ng/mL) were observed in 28%, but only 9% had 25OHD deficiency (<20 ng/mL). In the whole group, 25OHD levels negatively correlated with body mass index (r = -0.33, P = .0005), PTH (r = -0.30, P = .001), calcium (r = -0.29, P = .002), renal function, and PHPT duration. CV indices were normal except for carotid intima-media thickness, stiffness, and plaque thickness, which were increased, regardless of 25OHD status. Isovolumic relaxation time was the only CV measure associated with 25OHD (r = -0.26, P = .01). Those with 25OHD less than 20 ng/mL had more severe PHPT and a higher rate of nephrolithiasis. Those with 25OHD less than 30 ng/mL were younger, had higher body mass index, had lower serum phosphate, and were more likely to be male, nonwhite, and Hispanic. Other than lower tissue Doppler e' and higher isovolumic relaxation time within normal range in those with 25OHD less than 30 vs greater than 30 ng/mL, there were no differences in CV indices using either 25OHD threshold., Conclusions: Patients with mild PHPT have subclinical carotid abnormalities, but low 25OHD is not associated with abnormal carotid or cardiac measures. To the extent that PTH levels differentiated those with 25OHD less than 20 but not 30 ng/mL, these data support a 25OHD threshold of 20 ng/mL as clinically relevant in PHPT.

Background: Vitamin D deficiency is associated with cardiovascular disease such as coronary artery disease, heart failure, and hypertension. Vitamin D deficiency activates the renin-angiotensin-aldosterone system, which affects the cardiovascular system. For this reason, it could be suggested that there is a relationship between vitamin D deficiency and atrial fibrillation (AF). In our study, we compared 25-hydroxyvitamin D (25-OHD) levels between nonvalvular AF, valvular AF, and control groups in sinus rhythm., Method: A total of 102 patients with nonvalvular chronic AF without any other cardiovascular disease (mean age 62.51 ± 5.88; group I) and 96 patients with AF, which is associated with mitral valve disease (mean age 61.51 ± 5; group II) were included in our study. Of all, 100 age-matched healthy people with sinus rhythm were accepted as control groups (mean age 61.35 ± 5.44). Routine biochemical parameters, 25-OHD and parathormone levels were performed., Results: Baseline characteristics of the study groups were comparable. Group I patients had a lower vitamin D level than group II and the control group (6.51 ± 4.89, 9.24 ± 7.39, and 11.18 ± 6.98 ng/mL, P < .001, respectively). In groups I and II, the patients' left atrium diameter and systolic pulmonary artery pressure are higher than the control group., Conclusion: As a result, our study revealed a relationship between vitamin D deficiency and nonvalvular AF.

Background: High resolution μCT, and combined μPET/CT have emerged as non-invasive techniques to enhance or even replace dual energy X-ray absorptiometry (DXA) as the current preferred approach for fragility fracture risk assessment. The aim of this study was to assess the ability of µPET/CT imaging to differentiate changes in rat bone tissue density and microstructure induced by metabolic bone diseases more accurately than current available methods., Methods: Thirty three rats were divided into three groups of control, ovariectomy and vitamin-D deficiency. At the conclusion of the study, animals were subjected to glucose ((18)FDG) and sodium fluoride (Na(18)F) PET/CT scanning. Then, specimens were subjected to µCT imaging and tensile mechanical testing., Results: Compared to control, those allocated to ovariectomy and vitamin D deficiency groups showed 4% and 22% (significant) increase in (18)FDG uptake values, respectively. DXA-based bone mineral density was higher in the vitamin D deficiency group when compared to the other groups (cortical bone), yet μCT-based apparent and mineral density results were not different between groups. DXA-based bone mineral density was lower in the ovariectomy group when compared to the other groups (cancellous bone); yet μCT-based mineral density results were not different between groups, and the μCT-based apparent density results were lower in the ovariectomy group compared to the other groups., Conclusion: PET and micro-CT provide an accurate three-dimensional measurement of the changes in bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity. As osteomalacia is characterized by impaired bone mineralization, the use of densitometric analyses may lead to misinterpretation of the condition as osteoporosis. In contrast, µCT alone and in combination with the PET component certainly provides an accurate three-dimensional measurement of the changes in both bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity.

Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Fracture susceptibility in the context of low vitamin D has been primarily associated with defective mineralization of collagenous matrix (osteoid). However, bone's fracture resistance is due to toughening mechanisms at various hierarchical levels ranging from the nano- to the microstructure. Thus, we hypothesize that the increase in fracture risk with vitamin D deficiency may be triggered by numerous pathological changes and may not solely derive from the absence of mineralized bone. We found that the characteristic increase in osteoid-covered surfaces in vitamin D-deficient bone hampers remodeling of the remaining mineralized bone tissue. Using spatially resolved synchrotron bone mineral density distribution analyses and spectroscopic techniques, we observed that the bone tissue within the osteoid frame has a higher mineral content with mature collagen and mineral constituents, which are characteristic of aged tissue. In situ fracture mechanics measurements and synchrotron radiation micro-computed tomography of the crack path indicated that vitamin D deficiency increases both the initiation and propagation of cracks by 22 to 31%. Thus, vitamin D deficiency is not simply associated with diminished bone mass. Our analyses reveal the aged nature of the remaining mineralized bone and its greatly decreased fracture resistance. Through a combination of characterization techniques spanning multiple size scales, our study expands the current clinical understanding of the pathophysiology of vitamin D deficiency and helps explain why well-balanced vitamin D levels are essential to maintain bone's structural integrity.

Aim: The aim of the study is to establish whether healthy full-term breastfed infants require supplemental vitamin D for proper bone mineralization., Methods: Bone mineralization was studied by performing ultrasound scans of 73 healthy full-term subjects at the age of 3 months. The infants were divided into three groups. Group A: breastfed without supplemental vitamin D (BF); group B: breastfed with supplement of 400 IU/day of vitamin D (BFD); group C: fed with formula (with and without supplemental vitamin D 400 IU/day) (FF). The values of mcSOS (m/sec) and mcBTT (µsec) were assessed in all subjects., Results: A statistically significant difference has been found between group A vs group B both in mcSOS (P=0.03) and in mcBTT (P=0.01) values and also between group A vs group C both in mcSOS (P=0.012) and in mcBTT (P=0.003) values. Significant differences between group B vs group C were not found. In 75% of subjects of group A mcSOS and mcBTT values were ≤ the 10th percentile, while in group B they were between the 10th and 50th percentile. In FF infants given supplemental vitamin D mcSOS and mcBTT values were between the 25th and 75th percentile., Conclusion: Human breast milk is an appropriate source of nutrition for the growth of healthy full-term newborns, but is poor in vitamin D as demonstrated by the impaired bone mineralization in the breastfed infants without supplemental vitamin D. The results presented demonstrate that exclusively breastfed infants require at least 400 IU/day of supplemental vitamin D.