Objective: The aim of this study was to investigate the relationship between primary monosymptomatic enuresis nocturna (PMNE) and vitamin D deficiency in children. Patients and Methods: This retrospective case-control study included 307 PMNE patients aged 5-18 years and 254 age- and sex-matched healthy control subjects. Demographic data and biochemical parameters of the participants were obtained from hospital records. Serum 25(OH)D3 levels were measured using the chemiluminescence immunoassay method. The Mann-Whitney U test, Chi-square test, Pearson correlation and multivariate logistic regression analysis were used for statistical analyses. Results: Serum 25(OH)D3 levels were significantly lower in the PMNE group compared to the control group (p < 0.001). The rate of vitamin D deficiency was higher in the PMNE group. Vitamin D deficiency (OR: 3.164, 95% CI: 1.195-8.378, p = 0.02) and family history of enuresis (OR: 2.790, 95% CI: 1.01-5.8, p = 0.04) were found to be independent associated factors for PMNE. A significant negative correlation was found between serum vitamin D level and weekly bedwetting frequency (r = -0.377, p < 0.001). Conclusions: Serum 25(OH)D3 levels were significantly lower in the PMNE group (p < 0.001, Cohen's d = 0.89). It is recommended that vitamin D levels should be routinely evaluated in children with PMNE and the potential benefits of vitamin D supplementation should be investigated in prospective studies.

Vitamin D is a prohormone necessary for the optimal functioning of the locomotor and circulatory systems in humans. As a caveat, vitamin D metabolism is crucial for maintaining musculoskeletal and cardiovascular health for overexercising people, like athletes. Our study intended to explore the relationship between serum 25-hydroxy vitamin D (25(OH) D) levels and left ventricle/right ventricle (LV/RV) systolic and diastolic function in adolescent athletes using 2D Doppler studies.

In our cross-sectional study, 100 adolescent athletes were divided into two groups: vitamin D insufficiency (25(OH)D<20 ng/mL) and vitamin D sufficiency (25(OH)D>20 ng/mL) with 30 males and 20 females in both groups. A detailed physical examination and basic biochemical tests were performed; serum 25(OH)D levels were determined, and an echocardiographic evaluation was performed.

We found that decreased serum 25(OH)D levels were associated with impairment in many indicators of cardiac function, such as left ventricular-right ventricular-interventricular septum peak systolic velocity (Sm) and Tei index, inflow peak early diastolic velocity and inflow peak late diastolic velocity ratio (E/A), annulus early diastolic myocardial peak velocity (E'), and E/E' ratio.

To protect cardiac functions in adolescent athletes, we suggest screening serum 25(OH) D levels during certain periods, such as fall and winter, and vitamin D supplementation if necessary.

Snijders Blok-Campeau syndrome (SNIBCPS, OMIM#618205) is an autosomal dominant neurodevelopmental disorder attributed to pathogenic variants in the chromodomain helicase DNA binding protein 3 (CHD3) gene. To date, more than 100 individuals have been diagnosed with SNIBCPS. The syndrome is characterized by intellectual disability, global developmental delay, speech or language impediments, and dysmorphic features associated with macrocephaly. Additionally, affected individuals may exhibit behavioral issues, hypotonia, and autistic traits. A novel splicing variant (c.5590+1G > T) in the C-terminal 2 region of the CHD3 gene was identified in a patient predominantly exhibiting autistic characteristics. In vitro minigene splicing experiments conducted in HEK293 cells revealed that aberrant splicing resulted in the formation of a cryptic site 46 nucleotides downstream of the 5' splice site. This alteration was predicted to disrupt the reading frame by eliminating the physiological stop codon, consequently causing an extension in protein translation. Furthermore, an additional patient presenting with hypotonia, dysmorphic features, and global developmental delay was documented. This patient harbored a missense variant in the helicase C-terminal domain, c.3505C > T (p. Arg1169Trp). The pathogenic variant was anticipated to impact chromatin remodeling capacity and enzyme activity. Given the high prevalence of arginine residue pathogenic variants in the CHD3 protein and its notable propensity for binding and storing ATP molecules, intriguing insights into the potential effects of arginine residue pathogenic variants on phenotypes are provided. These findings contribute to a more comprehensive understanding of the genetic landscape of SNIBCPS while elucidating potential molecular mechanisms underlying the syndrome.

The importance of vitamin D for a well-functioning immune system is becoming increasingly evident. Nevertheless, the other fat-soluble vitamins A, E and K also seem to play a central role regarding the adequate function of immune cells and to counteract excessive immune reactions and inflammatory processes. However, recognizing hidden hunger, particularly micronutrient deficiencies in vulnerable groups like the elderly, is crucial because older adults often lack sufficient micronutrients for various reasons. This review summarizes the latest findings on the immune modulating functions of fat-soluble vitamins in a physiological and pathophysiological context, provides a graphical comparison of the Recommended Daily Allowances between Deutschland, Austria, Confoederatio Helvetica (D-A-CH; eng. GSA, Germany, Switzerland, Austria), Deutsche Gesellschaft für Ernährung (DGE; eng. German Nutrition Society) and National Institutes of Health (NIH) across all age groups and, in particular, addresses the question regarding the benefits of supplementation of the respective micronutrients for the aging population of industrialized nations to strengthen the immune system. The following review highlights the importance of fat-soluble vitamins A, D, E and K which play critical roles in maintaining immune system function and, in some cases, in preventing excessive immune activation. Therefore, a better understanding of the relevance of adequate blood levels and consequently potential supplementation strategies may contribute to the prevention and management of infectious diseases as well as better overall health of the elderly.

Immune function is affected by vitamin D status, but the optimal serum 25-hydroxy vitamin D [25(OH)D] concentration for immune function is not known.

We hypothesized that 25(OH)D would be associated with markers of inflammation and immune activation.

We identified associations between 25(OH)D and immune markers from 361 healthy adults using polynomial regression. Linear regression was used to define the slope (β) of significant linear associations, and piecewise regression identified inflection points (IPs) for curvilinear associations with P < 0.05. IPs with a slope difference (SD) P < 0.05 before and after were significant.

25(OH)D had linear, negative associations with interleukin (IL)-6 (β: -0.126; P = 0.009) and macrophage-derived chemokine (MDC) (β: -0.108; P = 0.04) and a linear, positive association with matrix metalloproteinase (MMP)-1 (β: 0.108; P = 0.04). Among the significant curvilinear associations, 2 showed negative associations below but positive associations above an IP with nearly significant SD P values, including percentage of effector-memory CD8 T cells (IP: 56.2 nmol/L; SD P = 0.067) and platelet concentration (IP: 38.9 nmol/L; SD P = 0.058). The opposite associations, positive below and negative above an IP, were seen for eotaxin (IP: 49.5 nmol/L; SD P = 0.049); interferon (IFN)-γ-induced protein-10 (IP-10) (IP: 71.8 nmol/L; SD P = 0.02); percentage of CD4 T cells expressing programmed cell death protein (PD)-1 (IP: 71.2 nmol/L; SD P = 0.01); percentage of Tregs expressing human leukocyte antigen, DR isotype (HLA-DR) (IP: 67.5 nmol/L; SD P < 0.0001); percentage of memory Tregs (IP: 68.8 nmol/L; SD P = 0.002); and percentage of memory Tregs expressing HLA-DR (IP: 68.8 nmol/L; SD P = 0.0008).

These findings are consistent with low vitamin D status allowing and higher vitamin D status dampening inflammation and immune activation. IP analysis identified possible thresholds for vitamin D effects on immune function. Two of 3 IPs at ∼50 nmol/L show higher inflammation below this concentration, suggesting 50 nmol/L as a minimum target for dampening inflammation. IPs at ∼70 nmol/L identify a threshold for CD4 T-cell activity, including Treg activation and IFN-γ-driven production of the T-cell chemokine IP-10, suggesting an optimal concentration for regulating adaptive immunity. This study was registered at clinicaltrials.gov as NCT02367287.

To investigate the prevalence of vitamin D deficiency (VDD) in children/adolescents in extreme southern China.

This multicenter, cross-sectional study included 21,811 children aged 0-18 years from 18 districts in Hainan Province, using a multistage stratified random sampling method from January 2021 to March 2022.

Serum 25(OH)D levels decreased with age (p trend <0.001). VDD prevalence increased significantly from 3.7% (95% CI: 3.2, 4.3) in children aged 0-3 years to 43.5% (95% CI: 42.1, 45.0) in those aged 13-18 years. Girls and urban residents showed higher deficiency rates. Adolescents (13-18 years) had the highest prevalence of VDD (43.5%), while toddlers (0-3 years) had the lowest (3.7%). Factors influencing vitamin D status included gender, urban residency, and breastfeeding duration. Seasonal variations showed higher deficiency rates in autumn, particularly among preschoolers. Regional differences were noted, with the highest deficiency in semiarid and subhumid zones for various age groups.

A significant increase in VDD with age, particularly among adolescents, urban girls, and during autumn, emphasizing the need for targeted strategies.

This study evaluated the causal relationship between childhood obesity and vitamin D levels by performing a Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) summary statistics. To mitigate bias stemming from confounding and reverse causation, we conducted an MR analysis to assess the causal impact of childhood obesity on the major circulating form of vitamin D, 25-hydroxyvitamin D (25(OH)D).

Vitamin D is present in the blood in the form of 25(OH)D; childhood obesity and 25(OH)D levels data were obtained from the IEU open GWAS project, which were subjected to MR analyses. The IVW method was used as the predominant analysis method and was complemented by MR-Egger, simple mode, weighted median, and weighted mode methods. The MR-PRESSO method was utilized to identify horizontal pleiotropy and potential outliers.

This study indicated that childhood obesity affects the serum of 25(OH)D, which was significant in the IVW (OR [95%CI], 0.977 [0.966-0.989], p = 0.0001), and weighted-median (OR [95%CI], 0.983 [0.969-0.997], p = 0.015) analyses, but nonsignificant in the MR-Egger (OR [95%CI], 0.985 [0.897-1.082], p = 0.784), simple mode (OR [95%CI], 0.985 [0.965-1.005], p = 0.233), and weighted mode (OR [95%CI], 0.985 [0.967-1.004], p = 0.214) analyses.

In summary, we found a potential inverse association between elevated childhood obesity and 25(OH)D levels, which suggested that obese children need to pay attention to their 25(OH)D levels, and vitamin D supplementation may be necessary when needed.

Numerous observational studies have demonstrated a significant inverse association between vitamin D status and the risk of major chronic disease, including type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. However, findings from Mendelian randomization (MR) studies and randomized controlled trials (RCTs) suggest minimal or no benefit of increased vitamin D levels. We provide an overview of recent literature linking vitamin D to major chronic diseases. Because emerging evidence indicates a potential threshold effect of vitamin D, future well-designed studies focused on diverse populations with vitamin D deficiency or insufficiency are warranted for a more comprehensive understanding of the effect of maintaining sufficient vitamin D status on the prevention of major chronic diseases.

The timeline of alteration of vitamin D and calcium levels in those receiving anti-seizure medication (ASM) remains to be elucidated. To determine the changes in vitamin D levels over a period of 6 months among children receiving monotherapy with commonly used ASM.

The baseline serum levels of vitamin D, parathyroid hormone (PTH), calcium, alkaline phosphatase (ALP), phosphorus were measured in 32 children (median age 8 years) with newly diagnosed epilepsy. An appropriate ASM monotherapy was started. Those found to be deficient were treated with vitamin D supplementation. Children were reassessed after 90 days and 180 days for drug compliance and drug side-effects. All the baseline investigations were repeated.

At baseline, 21.9% of children were vitamin D-deficient, with a median serum level of 19.8 ng/mL. For children who were not vitamin D-deficient (VDD) at baseline (n=25), the median (interquartile range [IQR]) vitamin D levels were found to be significantly lower than baseline after 90 days of ASM use (23.0 [18.0 to 28.9] vs. 22.0 [12.0 to 24.0]; p<0.001). After 90 days, ASMs caused notable decreases in vitamin D levels from baseline for children who were not VDD at baseline (n=25) (23.0 [18.0 to 28.9] vs. 22.0 [12.0 to 24.0]; p<0.001), alongside changes in calcium, phosphorus, PTH and ALP levels. Similarly, in children who were non-deficient at 90 days follow-up (n=20), median (IQR) vitamin D levels were found to be significantly lower at 180 days than at 90 days (24.5 [21.0 to 28.9] vs. 18.4 [13.6 to 20.6]; p<0.001).

The study noted vitamin D deficiency in children on ASM monotherapy for 3-6 months, emphasizing regular monitoring by clinicians.

In December 2019, the so-called "coronavirus disease 2019" (COVID-19) began. This disease is characterized by heterogeneous clinical manifestations, ranging from an asymptomatic process to life-threatening conditions associated with a "cytokine storm". This article (narrative review) summarizes the epidemiologic characteristics and clinical manifestations of COVID-19 and multi-system inflammatory syndrome in children (MIS-C). The effect of the pandemic confinement on vitamin D status and the hypotheses proposed to explain the age-related difference in the severity of COVID-19 are discussed. The role of vitamin D as a critical regulator of both innate and adaptive immune responses and the COVID-19 cytokine storm is analyzed. Vitamin D and its links to both COVID-19 (low levels of vitamin D appear to worsen COVID-19 outcomes) and the cytokine storm (anti-inflammatory activity) are detailed. Finally, the efficacy of vitamin D supplementation in COVID-19 is evaluated, but the evidence supporting vitamin D supplementation as an adjuvant treatment for COVID-19 remains uncertain.

Vitamin D deficiency is linked to poor cancer outcomes but the impact of its consequence, elevated parathyroid hormone (PTH), remains understudied. PTH receptor activation influences cancer progression in vitro, yet the effect of elevated PTH on pediatric cancer survival is unexamined.

This retrospective study examines associations between PTH, 25-OH vitamin D (25OHD), and event-free survival (EFS) and overall survival (OS) in patients with pediatric cancer. Laboratory data from 4,349 patients (0-18 years) at a tertiary pediatric cancer unit were analyzed for the highest PTH and lowest 25OHD levels at diagnosis and the following 5 years. Data on relapse, secondary malignancies, and mortality were stratified by PTH levels above/below the cohort median (47 pg/mL) and 25OHD levels ≤30 nmol/L. EFS and OS were analyzed and hazard ratios (HR) were calculated for the entire cohort and six cancer subgroups.

PTH and 25OHD values were available for 1,286 patients (731 male). Higher PTH associated with inferior EFS in primary malignant brain tumors [HR, 1.80 (1.19-2.72)], embryonal malignancies [HR, 2.20 (1.1-4.43)], and lymphatic malignancies [HR 1.98 (1.05-3.72)]. Vitamin D deficiency associated with inferior EFS in embryonal malignancies [HR 2.41 (1.24-4.68)]. In a multivariate Cox model, only higher PTH remained significant for inferior EFS.

Elevated PTH may indicate adverse outcomes in certain pediatric cancers.

This study identifies elevated parathyroid hormone as a potential marker for poor outcomes in patients with pediatric cancer, emphasizing the need for adequate vitamin D and calcium management.

Compare the efficacy and safety of daily versus fortnightly oral vitamin D3 in treating symptomatic vitamin D deficiency in children aged 1-10 years.

Open labelled randomized controlled trial.

Eighty children with symptomatic vitamin D deficiency were randomized into group daily (D) and group bolus (B) [40 in each group] to receive oral vitamin D3, 4000 IU daily or 60,000 IU fortnightly for 12 weeks respectively. Both groups received daily oral calcium of 500 mg/day.

Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol (25(OH)D), parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 weeks and 12 weeks. At the end of 12 weeks, 74 children were available for evaluation of the efficacy and safety of both regimens.

Both regimens led to a significant increase in Ca and P levels and a fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no intergroup difference. At 4- and 12-week assessments, all children in both treatment arms achieved 25(OH)D level in sufficiency range, with no significant difference in their geometric mean. Both regimens were associated with asymptomatic transient hypercalcemia [group D-51.4% vs. group B-34.3%; p -0.14] and hypercalciuria (5.7%) in group D that resolved spontaneously on follow-up.

Daily and fortnightly oral vitamin D3 in similar cumulative doses are efficacious for treating symptomatic vitamin D deficiency in children (1-10 years). Treated children should be monitored for serum 25(OH)D, Ca and urinary calcium creatinine ratio.

Background: the relationship between vitamin D deficiency and carotid intima-media thickness (CIMT) in children and adolescents with obesity is unknown. The aim of this study was to investigate the correlation between vitamin D levels and CIMT in children and adolescents with obesity. Methods: a total of 440 children and adolescents aged 6-16 with obesity were included in the study. Anthropometric measurements, blood pressure measurements, blood lipids, blood glucose, and vitamin D levels were measured. Bilateral carotid ultrasound was performed to assess CIMT. The relationships between vitamin D levels and CIMT were assessed using multivariate linear regression with Generalized Linear Models and restricted cubic splines. Binary logistic regression analyses were conducted to explore the association between vitamin D status and the risk of abnormal CIMT. Results: vitamin D levels were inversely correlated with CIMT in subjects with serum 25-hydroxyvitamin D [25(OH)D] levels less than or equal to 50 nmol/L (ß = -0.147, 95 % CI [-0.263, -0.030], p = 0.013), but this correlation was not significant in subjects with serum 25(OH)D levels above 50 nmol/L. After correcting for various confounders, the risk of abnormal CIMT was significantly higher in the vitamin D deficiency group (OR = 2.080, 95 % CI [1.112, 3.891], p = 0.022). Conclusions: vitamin D deficiency is an independent risk factor for abnormal CIMT, and vitamin D deficiency may play a promoting role in the atherosclerotic process in children and adolescents with obesity.

The osteological paradox recognizes that the presence of lesions is not always directly related with increased mortality. When combined with the clinical, historical, and epidemiological literature on scurvy, survivorship analysis, a form of statistical analysis to assess the relationship between the presence of diseases in the archeological record and survival, helps determine the overall burden of the disease both in terms of morbidity and mortality. This article explores the relationship between scurvy and survivorship in 26 adults from Man Bac, a Neolithic site from northern Vietnam together with prepublished evidence of scurvy in the nonadult population (n = 44).

Diagnosis of scurvy included differential diagnosis combined with the Snoddy, A. M. E., Buckley, H. R., Elliott, G. E., Standen, V. G., Arriaza, B. T., & Halcrow, S. E. (2018). Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide. American Journal of Physical Anthropology, 167(4), 876-895. https://doi.org/10.1002/ajpa.23699 threshold criteria and the Brickley, M. B., & Morgan, B. (2023). Assessing diagnostic certainty for scurvy and rickets in human skeletal remains. American Journal of Biological Anthropology, 181, 637-645 diagnostic certainty approaches. Kaplan-Meier survival curves were produced to assess the relationship between the presence of probable scurvy and age-at-death.

The prevalence of probable scurvy in adults (35%) was considerably lower than reported for the nonadults (80%). Almost all lesions observed in the adults were in a mixed stage of healing. Kaplan-Meier analysis demonstrated no difference in survivorship between infants and children (<15 years) with or without probable scurvy, whereas a meaningful difference was observed for the adults and adolescents (15+ years).

The findings demonstrate that scurvy considerably decreased survivorship to older age categories. The degree of lesion remodeling, however, indicates that scurvy was not necessarily the direct cause of death but contributed to an overall disease burden that was ultimately fatal.

An adequate vitamin D level is essential for optimal bone mass formation during growth. The present study aimed to assess (i) the sex-specific, age-specific, and potential seasonal (spring, summer, winter) influences on the pediatric circulating levels of 25-hydroxyvitamin D (25(OH)D); (ii) determine the frequency of pediatric patients with vitamin D deficiency (VDD) or insufficiency (VDI); and (iii) quantify the association between age category, sex, and season types and susceptibility to VDD and VDI, respectively. Laboratory data were collected on serum 25(OH)D levels in children aged between 2 and 18 years (n = 1674) who underwent blood sampling following admission to a university pediatric hospital in Cluj-Napoca (Romania) between January and June 2023. VDD (<20 ng/mL) was observed in 27% of pediatric patients. Among toddlers and preschoolers (2-5 years), VDD was 11%, while it was 33% among school-aged children (6-11 years) and 39% among adolescents (12-18 years). We found a significant difference in the frequencies of vitamin D status between females and males (p = 0.006). Also, we found significant associations of vitamin D status with age categories (p < 0.0001) and seasonal variations (p = 0.03). After adjusting for season of blood collection, the multinomial logistic regression model showed that children aged 6-11 years old (adjusted OR = 7, 95% CI: (4.9, 9.4)), children aged 12-18 years old (adjusted OR = 14, 95% CI: (9.3, 19.6)), and females (adjusted OR = 1.43, 95% CI: (1.10, 1.86)) were significantly associated with higher odds of VDD. In conclusion, the study revealed a significant difference in the frequency of VDD and VDI among pediatric patients older than six years, with a significant difference according to sex and season, being more pronounced among girls and during the winter and spring seasons.

Vitamin D3 (VD3) deficiency among children in Saudi Arabia remains a pressing concern due to its poor bioavailability and the limitations of current pediatric formulations. To address this challenge, we developed a groundbreaking pediatric self-nanoemulsifying drug delivery system (Bio-SNEDDS) for VD3, fortified with black seed oil and moringa seed oil for dual therapeutic benefits. Through meticulous formulation optimization using ternary phase diagrams and comprehensive testing, our Bio-SNEDDS demonstrated exceptional performance.

Bio-SNEDDS were manufactured by incorporating Black seed oil and moringa seed oil as bioactive nutraceutical excipients along with various cosurfactant and surfactants. Bio-SNEDDS were systematically optimized through ternary phase diagrams, visual tests, droplet size analysis, drug solubilization studies, dispersion assessments, and pharmacokinetic testing in rats compared to Vi-De 3®.

Pseudoternary phase diagrams identified oil blends producing large nanoemulsion regions optimal for SNEDDS formation. The optimized F1 Bio-SNEDDS showed a mean droplet diameter of 33.7 nm, solubilized 154.46 mg/g VD3 with no metabolite formation, and maintained >88% VD3 in solution during 24 h dispersion testing. Notably, in vivo pharmacokinetic evaluation at a high VD3 dose demonstrated an approximately two-fold greater relative bioavailability over Vi-De 3®, validating the superb oral delivery performance of Bio-SNEDDS even under challenging high-dose conditions.

The Bio-SNEDDS provides an effective VD3 delivery strategy with established in vivo superiority over marketed products, along with offering additional health benefits from the natural oils.

A 15-month-old African American male patient presented to the pediatric clinic to establish care. The patient had been seen and treated by a previous pediatrician who had diagnosed him with failure to thrive, anemia, and hepatosplenomegaly, according to the patient's parents. Upon physical examination, the patient was determined to be less than the first percentile for height and in the eighth percentile for weight. Frontal bossing was also observed. The patient's hemoglobin level was measured in the office to help confirm the previous anemia diagnosis and was determined to be 6.3 g/dL (normal: 10.5-13.0 g/dL). At this point, the patient was sent to a pediatric emergency department for continued treatment and workup. At the emergency department, the patient received an extensive laboratory workup for the evaluation of anemia, revealing iron deficiency anemia (hemoglobin: 5.6 g/dL (normal: 10.5-13 g/dL), mean corpuscular volume: 51.4 fl (normal: 70-84 fl), iron: 18 mcg/dL (normal: 30-70 mcg/dL), total iron binding capacity: 598 mcg/dL (normal: 100-400 mcg/dL), and hematocrit: 23.7% (normal: 33-38%)) and decreased levels of vitamin D (<6 ng/mL, normal: >30 ng/mL), ionized calcium (1.17 mg/dL, normal: 4.4-5.2 mg/dL), and phosphorus (2.4 mg/dL, normal: 2.9-5.9 mg/dL). These studies, paired with X-ray images of the patient's shoulders and wrists, further confirmed the diagnosis of rickets. Rickets is a disease in pediatric patients defined as a condition in which the mineralization of epiphyseal plates is defective. A nutritional deficiency in vitamin D, calcium, or phosphate causes acquired rickets. This condition is most commonly found in developing countries; some predisposing factors include poor sun exposure, high altitude, and breastfeeding. The patient was seen in the outpatient pediatric setting after the hospitalization, in which he received a blood transfusion, where he was managed on supplementation of calcium carbonate suspension, polysaccharide iron complex/novaferrum drops, and cholecalciferol drops with referral to endocrinology, hematology, and dietetics. This case serves as an example of how the diagnosis of nutritional deficiencies, such as rickets, can also be found in developed countries like the United States. Other conditions considered in the differential diagnosis were cystic fibrosis, necrotizing enterocolitis, metabolic disorders, inadequate absorption, and mechanical feeding difficulties, each of which must be ruled out to ensure that even an unlikely finding was not missed.

International and observational epidemiological studies provide evidence that vitamin D deficiency may confer increased risk of influenza and respiratory tract infection. This study was undertaken to evaluate the prevalence of vitamin D deficiency in pneumonia in children, and to assess its relationship with the severity.

Study group included children aged between 2 months to 5 years of age admitted as inpatients who presented with clinical features of pneumonia as per WHO Classification. Detailed clinical assessment and physical examination was done at the time of admission and patients were enrolled and relevant findings were noted in prestructured proforma. Vitamin D levels <30 nmol/L (<12 ng/mL) were defined as deficient, 30-50 nmol/L (12-20 ng/mL) as insufficient, and >125 nmol/L (>50 ng/mL) as sufficient. Outcomes of the patients admitted were recorded in terms of duration of hospitalization, Intensive Care Unit (ICU) stay, oxygen requirement, antibiotic need and duration, need for upgradation of antibiotics, nebulization need with drugs used, ventilator need and other parameters. Statistical analysis was performed using statistical package for social sciences software (SPSS Inc., Chicago, IL, USA). A P value of <0.05 was considered statistically significant.

Out of 101 patients, 100% presented with fever, cough and fast breathing, 42.6% with grunting, 41 (40.5%) with noisy breathing, 5.7% with bluish discoloration, and 4.3% with apnea. Forty-one (40.5%) patients had crepitation, 53 (52.4%) patients had rhonchi, while 7 (6%) presented with bronchial breathing. Chest radiography features at admission helped to differentiate between presumed viral and presumed bacterial infection. Vitamin D deficient patients had significantly longer duration of hospital stay as compared to vitamin D sufficient group (P<0.001). The need for upgradation of antibiotics between the three groups were found to be significant (P<0.001). This showed that vitamin D deficiency is directly proportional to the need of upgradation of antibiotics. Bacterial pneumonia presents mostly as alveolar infiltrates and/or pleural effusion while viral pneumonia presents as interstitial infiltrates and/or hyperinflation. Cases with presumed bacterial pneumonia (based on X-ray, 38 out of 48, 79.1%) were more often vitamin D deficient as compared to case with presumed viral pneumonia (32 out of 52, 61.5%, P=0.05).

Vitamin D is widely prevalent in Indian children with pneumonia. Vitamin D deficient patients needed a longer duration of hospitalization, more upgradation of antibiotics, and PICU admissions; moreover, it had more CPAP requirement, longer duration of PICU stay and longer duration of CPAP requirements as compared to vitamin D sufficient group.

Vitamin D deficiency is a common problem in exclusively breastfed infants, with supplementation recommended by various international medical organizations. However, in Thailand, no advice for routine vitamin D supplementation is available. Thus, this study investigated the prevalence of vitamin D deficiency and its associated factors in exclusively breastfed infants in Bangkok, Thailand.

To investigated the prevalence of vitamin D deficiency and its associated factors in exclusively breastfed infants in Bangkok, Thailand.

This descriptive observational cross-sectional study assessed 109 4-month-old infants at Charoenkrung Pracharak Hospital from May 2020 to April 2021. The 25-OH vitamin D level of the infants was measured using an electrochemiluminescence binding assay. Vitamin D deficiency was defined as 25-OH level < 20 ng/mL, with vitamin D insufficiency 20-30 ng/mL. The sun index and maternal vitamin D supplementation data were collected and analyzed using the independent t-test, univariate logistic regression, and multivariate logistic regression to identify the associated factors.

The prevalences of vitamin D deficiency and vitamin D insufficiency were 35.78% and 33.03%, respectively with mean serum 25-OH vitamin D levels in these two groups 14.37 ± 3.36 and 24.44 ± 3.29 ng/mL. Multivariate logistic regression showed that the main factors associated with vitamin D status were maternal vitamin D supplementation and birth weight, with crude odds ratios 0.26 (0.08-0.82) and 0.08 (0.01-0.45), respectively. The sun index showed no correlation with the 25-OH vitamin D level in exclusively breastfed infants (r = -0.002, P = 0.984).

Two-thirds of healthy exclusively breastfed infants had hypovitaminosis D. Vitamin D supplementation prevented this condition and was recommended for both lactating women and their babies.

Congenital ichthyoses (CI) comprise a heterogeneous group of monogenic genetic skin diseases characterized by diffuse scaling, often associated with skin inflammation. Diagnosis of the individual form of ichthyosis is complex and is guided by clinical expertise. CI usually has a major impact on quality of life (QOL) and thus requires lifelong treatment. To date, there are no curative therapies, although various symptomatic treatment options exist. The present protocol for the management of CI has been drawn up in accordance with the recommendations published in 2012 by the French National Authority for Health, based on a literature review, with the help and validation of members of the French network for rare skin diseases (FIMARAD). It provides a summary of evidence and expert-based recommendations and is intended to help clinicians with the management of these rare and often complex diseases.

Vitamin D deficiency may cause adverse effects on the cardiovascular system as well as many other systems. The risk of vitamin D deficiency increases during adolescence, when the growth rate is high, due to reasons such as limited sun exposure, inadequate dietary calcium, and vitamin D intake.

To evaluate the effect of daily 2000 IU vitamin D supplementation for 12 weeks on cardiac function in non-obese adolescent girls with vitamin D deficiency.

This cross-sectional study was carried out between September 2021 and June 2022. A total of 108 non-obese adolescent girls having 25-hydroxyvitamin D [25(OH)D] levels below 12 ng/mL were given daily 2000 IU vitamin D orally for 12 weeks. Serum levels of 25(OH)D, alkaline phosphatase, parathormone, calcium, phosphate, and cardiac function were determined before and after treatment.

After treatment, the 25(OH)D levels were above 20 ng/mL in 90.8% of the adolescents. The parathormone and alkaline phosphatase levels decreased, while the phosphate levels increased. Echocardiographic tissue Doppler studies showed positive changes in some systolic and diastolic function indicators. In addition, the myocardial performance index decreased from 0.42 ± 0.03 to 0.40 ± 0.03 (P < 0.001) in the left ventricle, from 0.43 ± 0.03 to 0.38 ± 0.03 (P < 0.001) in the right ventricle, and from 0.41 ± 0.04 to 0.38 ± 0.02 (P < 0.001) in the interventricular septum after vitamin D treatment as compared to pretreatment.

It was observed that administration of 2000 IU vitamin D treatment for a period of 12 weeks to non-obese adolescent girls with vitamin D deficiency contributed positively to cardiac systolic and diastolic function.

The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed.

This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals.

The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained.

Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (β: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (β: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (β: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 μg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (β: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 μg/L) and vitamin D (25(OH)D <75 nmol/L) (β: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients.

A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy.

The aim of this study was to evaluate the influence of serum 25-hydroxyvitamin D [25(OH)D] levels at birth in postnatal growth at discharge and 12 mo of corrected age in preterm infants.

This prospective cohort included 63 preterm newborns born before 34 gestational weeks evaluated from birth until 12 mo of corrected age. The serum 25(OH)D levels in umbilical cord blood and from their mothers were evaluated at delivery.

The mean 25(OH)D levels in preterm newborns were higher than maternal levels (24.8 ± 13.3 ng/mL versus 21 ± 10.2 ng/mL, P < 0.001) and showed a moderate correlation between (r = 0.548; P < 0.001). Considering the body mass index Z-score at 12 mo, 3 (10%), 25 (83%), and 2 (7%) of the preterm infants were thin, had normal body mass index, and were overweight, respectively. The 25(OH)D levels in the umbilical cord did not influence the anthropometric indicators at hospital discharge and 12 mo of corrected age. We observed improvement in all anthropometric indicators assessed over the months, and there was no difference between preterm infants with 25(OH)D levels >20 ng/mL and <20 ng/mL in the umbilical cord.

The results of this study suggested that the 25(OH)D serum levels in the umbilical cord did not influence postnatal growth from birth to the first year of life in preterm infants. There was a direct association between maternal and umbilical cord serum 25(OH)D levels.

Postnatally, severe vitamin D deficiency commonly results in rickets as well as potential defects in tooth mineralization. The effects of milder deficiency on oral health outcomes later in life are still unclear. This study used micro-computed tomography (μCT), energy dispersive X-ray analysis (EDX), and Raman spectroscopy to investigate mineral density, total density, and elemental composition of enamel and dentine in 63 exfoliated primary incisors from participants with known 25-hydroxyvitamin D levels (25-OHD) at birth. No differences in mineralization and chemical composition using μCT and EDX analysis were observed irrespective of 25-OHD status. Subtle structural differences were observed via Raman spectroscopy, with more crystalline enamel observed in those with sufficient 25-OHD at birth. Although subtle, the differences seen suggest further attention should be given to children with known milder levels of vitamin D deficiency in early life. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Rickets is a disorder caused by a lack of vitamin D, calcium or phosphate. It leads to softening and weakening of the bones. Dental manifestation of rickets includes enamel hypoplasia and delayed tooth eruption. The most important oral findings are characterised by spontaneous gingival and dental abscesses occurring without a history of trauma or caries. Radiographic examination revealed large pulp chambers, short roots, poorly defined lamina dura and hypoplastic alveolar ridge. These dental abscesses are common, and therefore, extraction and pulpectomy are the treatment of choice. Oral manifestations of rickets should be diagnosed early by both physicians and dentists to prevent severe dental complications. This article aims to report a case of rickets in a 3-year-old girl, describing the dental findings and the treatment to be performed in these cases.

The growing years are paramount for bone growth and mineral accrual. Children with long-term neurological condition (LTNC) have multiple risk factors for poor bone health and fragility fractures. In Singapore, this has not been studied systematically. Therefore, we aimed to evaluate the risk factors associated with fragility fractures in children with LTNC.

In this study, the search for fragility fractures was done by a retrospective review of patients with LTNC on follow-up in the paediatric neurology clinic and patients who presented with fracture to the paediatric orthopaedic clinic. Information on patients' demographics, medical history, intervention, biochemical bone markers and fracture history was collected.

In a tertiary clinic population of 136 patients with LTNC, 65% were dependent on mobility (Gross Motor Function Classification System [GMFCS] V), 60% were underweight and 60% were fed via gastrostomy or nasogastric tube, or were on oral pureed diet. Furthermore, 60% were on anticonvulsants. The fracture rate was 3% in this population and was associated with low-impact activities such as transfer and dressing. Only 7.4% and 33% of the patients had undergone measurements of vitamin D and calcium levels, respectively.

The local prevalence of fragility fractures in children with LTNC on follow-up at the neurology clinic was found to be 3%. Risk factors identified were limited ambulation and compromised nutritional status associated with feeding difficulty. Recommendations to optimise bone health in children with LTNC were made. These include promoting weight-bearing activities, looking out for underweight children, avoiding vitamin D deficiency and ensuring adequate calcium intake.

Our objective was to determine the prevalence of osteomalacia in low-energy hip fracture patients over the age of 45, based on biochemical and histological measures. This cross-sectional study included 72 patients over 45 with low-energy mechanism hip fractures. Samples of fasting venous blood were taken for hemograms and serum biochemistry analyses. Bicortical biopsies of the iliac crest were obtained, processed, and evaluated by an expert pathologist for osteomalacia. Biochemical osteomalacia (b-OM) is defined according to a distinct criterion. A low level of serum calcium, phosphorus, albumin, and 25OHD was found in 43.1, 16.7, 73.6, and 59.7% of patients, respectively. 50.0% of patients had high serum alkaline phosphatase (ALP) levels. b-OM was found in 30 (41.7%), and no significant association was found with PTH, Cr, Alb, age, sex, fracture type, side of the trauma, and season were not associated with osteomalacia. Osteomalacia was diagnosed on histopathological analysis in 19/72 (26.7%), and 54/72 (75.0%) of all cases fulfilled b-OM criteria. In the histologic evaluation, osteoid seam width, osteoid surface, and osteoid volume were 28.5 µm, 25.6, and 12.1%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the biochemical test for detecting osteomalacia were 73.6, 64.2, 42.4, 87.2, and 66.7%, respectively. Up to 30% of elderly patients with low-energy hip fractures are affected by osteomalacia. A biochemical screening along with a bone biopsy and histopathologic evaluation may be logical in a high-risk population for osteomalacia diagnosis.

Association of vitamin D (25(OH)D) deficiency with obesity and diabetes has been well-established in paediatric and adult populations. This study aims to report the association of 25(OH)D deficiency with body composition and prevalence of 25(OH)D deficiency in Emirati children and adolescents, who attended a diabetes centre in the United Arab Emirates.

Using Abu Dhabi Diabetes and Obesity Study cohort, type 1 diabetes (T1D) and normoglycaemic (NG) participants between 4-19 years of age were selected. WHO criteria were used to define 25(OH)D cut-offs: deficient (< 30 nmol/L), insufficient (30-50 nmol/L) and sufficient (> 50 nmol/L). Based on CDC recommendations, BMI percentile was categorised as underweight, normal weight, overweight and obesity.

After age and sex matching, 148 T1D cases and 296 NG controls were identified. 25(OH)D deficiency was observed in 22.3% (n = 33) T1D and 40.5% (n = 120) NG participants. 25(OH)D levels were lower in adolescents (15 - 19 years) than children (4 - 7 years) in both T1D and NG groups (p = 0.018 vs p < 0.001). Females were more likely to be 25(OH)D deficient in both groups. Children and adolescents with BMI ≥ 95^th percentile were more likely to be 25(OH)D deficient than those with normal weight (OR: 2.69; 95% CI: 1.56, 4.64). Adiposity measures and 25(OH)D levels correlated negatively in both groups (T1D p < 0.01, NG p < 0.001).

Vitamin D 25(OH)D deficiency is notably prevalent in Emirati children and adolescents despite adequate sunlight throughout the year. The prevalence was lower in those with T1D which may be indicative of treatment compliance in this population. This study also confirms important negative association of serum 25(OH)D levels with body mass and obesity in this population.

Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre-post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4-41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: -0.18 (95% CI: -0.36 to -0.01; I² = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.

Vitamin D deficiency in patients with cholestasis is due to impaired intestinal vitamin D absorption, which results from decreased intestinal bile acid concentration. Patients with cholestasis usually do not achieve optimal vitamin D status when a treatment regimen for children without cholestasis is used. However, data on high-dose vitamin D treatment in patients with cholestasis are limited.

This study is a prospective study that included pediatric patients with cholestasis (serum direct bilirubin > 1 mg/dL) who had vitamin D deficiency (serum 25-hydroxyvitamin D, 25-OHD, < 20 ng/mL). In Phase 1, single-day oral loading of 300,000 IU (or 600,000 IU if weight ≥ 20 kg) of vitamin D2 was administered, followed by an additional loading if serum 25-OHD < 30 ng/mL, and 4-week continuation of treatment using a vitamin D2 dose calculated based on the increment of 25-OHD after first loading. In Phase 2, oral vitamin D2 (200,000 IU/day) was administered for 12 days, followed by 400,000 IU/day of vitamin D2 orally for another 8 weeks if serum 25-OHD < 30 ng/mL.

Phase 1: Seven patients were enrolled. Three out of seven patients had a moderate increase in serum 25-OHD after loading (up to 20.3-27.2 ng/mL). These patients had conditions with partially preserved bile flow. The remaining four patients, who had biliary atresia with failed or no Kasai operation, had low increments of serum 25-OHD. Phase 2: Eleven patients were enrolled. Eight out of 11 patients had a moderate increase in serum 25-OHD after 200,000 IU/day of vitamin D2 for 12 days. Serum 25-OHD continued increasing after administering 400,000 IU/day of vitamin D2 for another 8 weeks, with maximal serum 25-OHD of 15.7-22.8 ng/mL.

Very high doses of vitamin D2 (200,000 and 400,000 IU/day) partly overcame poor intestinal vitamin D absorption and resulted in moderate increases in serum 25-OHD in pediatric patients with cholestasis, particularly when cholestasis was caused by uncorrectable bile duct obstruction.

Vitamin D plays a vital role in regulating calcium and phosphate metabolism and maintaining bone health. A state of prolonged or profound vitamin D deficiency (VDD) can result in rickets in children and osteomalacia in children and adults. Recent studies have demonstrated the pleiotropic action of vitamin D and identified its effects on multiple biological processes in addition to bone health. VDD is more prevalent in chronic childhood conditions such as long-standing systemic illnesses affecting the renal, liver, gastrointestinal, skin, neurologic and musculoskeletal systems. VDD superimposed on the underlying disease process and treatments that can adversely affect bone turnover can all add to the disease burden in these groups of children. The current review outlines the causes and mechanisms underlying poor bone health in certain groups of children and young people with chronic diseases with an emphasis on the proactive screening and treatment of VDD.

Compare the efficacy and safety of daily vs. monthly oral vitamin D₃ in treating symptomatic vitamin D deficiency in infants.

90 infants with symptomatic vitamin D deficiency were randomized into Daily (D) [46 infants] and Bolus (B) [44 infants] groups to receive oral vitamin D₃, daily (2000 IU/day) and bolus (60,000 IU/month) for three months respectively. Both groups received daily oral calcium @50 mg/kg/day. Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol [25(OH)D], parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 and 12 weeks. At the end of 12 weeks, 78 infants were available for evaluation of efficacy and safety of both regimens.

Both regimens led to a statistically significant increase in Ca and P levels and fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no inter-group difference. Infants in group D had statistically significant higher mean 25(OH)D levels as compared to group B at 4 weeks (group D 130.89 ± 43.43 nmol/L, group B - 108.25 ± 32.40 nmol/L; p - 0.012) and 12 weeks (group D - 193.69 ± 32.47 nmol/L, group B - 153.85 ± 33.60 nmol/L; p<0.001). Eight infants [group D - 6/41 (14.6 %); group B - 2/37 (5.4 %), p=0.268] developed mild asymptomatic hypercalcemia without hypercalciuria at 12 weeks that corrected spontaneously within a week.

Both daily and monthly oral vitamin D₃ in equivalent doses are efficacious and safe for treating symptomatic vitamin D deficiency in infants.

The term osteomalacia (OM) refers to a series of processes characterized by altered mineralization of the skeleton, which can be caused by various disorders of mineral metabolism. OM can be genetically determined or occur due to acquired disorders, among which the nutritional origin is particularly relevant, due to its wide epidemiological extension and its nature as a preventable disease. Among the hereditary diseases associated with OM, the most relevant is X-linked hypophosphatemia (XLH), which manifests in childhood, although its consequences persist into adulthood where it can acquire specific clinical characteristics, and, although rare, there are XLH cases that reach the third or fourth decade of life without a diagnosis. Some forms of OM present very subtle initial manifestations which cause both considerable diagnosis and treatment delay. On occasions, the presence of osteopenia and fragility fractures leads to an erroneous diagnosis of osteoporosis, which may imply the prescription of antiresorptive drugs (i.e., bisphosphonates or denosumab) with catastrophic consequences for OM bone. On the other hand, some radiological features of OM can be confused with those of axial spondyloarthritis and lead to erroneous diagnoses. The current prevalence of OM is not known and is very likely that its incidence is much higher than previously thought. Moreover, OM explains part of the therapeutic failures that occur in patients diagnosed with other bone diseases. Therefore, it is essential that clinicians who treat adult skeletal diseases take into account the considerations provided in this practical review when focusing on the diagnosis and treatment of their patients with bone diseases.

Vitamin D deficiency remains prevalent, with about 7% of the world's population living with severe vitamin D deficiency and about one third with mild deficiency. We compare the relative merits of calcifediol or 25-hydroxyvitamin D (25OHD) compared to vitamin D itself for supplementation as to prevent or cure vitamin D deficiency. The intestinal absorption of calcifediol is nearly 100% and thus higher than that of vitamin D itself. Moreover, calcifediol is absorbed by the intestinal cells and transported through the portal vein and thus immediately accessible to the circulation, while vitamin D is transported with chylomicrons through the lymph system. Therefore, in case of fat malabsorption or after bariatric surgery, calcifediol is much better absorbed in comparison with vitamin D itself. Serum 25OHD increases linearly with increasing doses of calcifediol, whereas serum 25OHD reaches a plateau when higher oral doses of vitamin D are used. Calcifediol, on a weight basis, is about 3 times more potent than vitamin D in subjects with mild vitamin D deficiency. This potency is even 6-8 times higher than vitamin D when baseline serum 25OHD is higher or when large doses are compared. In conclusion, calcifediol is an alternative option to correct vitamin D deficiency and may even be the preferred strategy in case of intestinal fat malabsorption, after bariatric surgery or in case of other conditions with suspected impaired 25-hydroxylase activity in the liver.

Rickets is the disease of a growing skeleton and results from impaired apoptosis of hypertrophic chondrocytes and mineralization of the growth plate. Nutritionally induced rickets, secondary to vitamin D and/or calcium deficiency, remains a major global problem. In this review, we discuss pathogenesis, clinical signs, investigation and management of nutritional rickets.

For more than two centuries, lack of sunlight has been understood to cause vitamin D deficiency and documented as a primary cause of rickets. As such, evidence of rickets in the archeological record has been used as a proxy for vitamin D status in past individuals and populations. In the last decade, a clinical global consensus has emerged wherein it is recognized that dietary calcium deficiency also plays a role in the manifestation of rickets and classic skeletal deformities may not form if dietary calcium is normal even if vitamin D is deficient. This disease is now clinically called "nutritional rickets" to reflect the fact that rickets can take calcium deficiency-predominant or vitamin D deficiency-predominant forms. However, there are currently no paleopathological studies wherein dietary calcium deficiency is critically considered a primary etiology of the disease. We review here the interplay of calcium, vitamin D, and phosphorous in bone homeostasis, examine the role of dietary calcium in human health, and critically explore the clinical literature on calcium deficiency-predominant rickets. Finally, we report a case of rickets from the late Formative Period (~2500-1500 years ago) of the Atacama Desert and argue the disease in this infant is likely an example of calcium deficiency-predominant rickets. We conclude that most archeological cases of rickets are the result of multiple micronutrient deficiencies that compound to manifest in macroscopic skeletal lesions. For clinicians, these factors are important for implementing best treatment practice, and for paleopathologists they are necessary for appropriate interpretation of health in past communities.

Adolescents with overweight/obesity are at risk for vitamin D insufficiency and deficiency. Both overweight/obesity and vitamin D insufficiency/deficiency may predispose to fractures. We enrolled 103 participants (53.3% females, 15.9 ± 2.2 years) in a retrospective case-control study to determine whether an association exists between fractures and a low 25-hydroxyvitamin D (25[OH]D) among adolescents whose body mass index (BMI) ≥ 85 percentile. Cases (n = 28) sustaining a low/medium impact fracture were matched to controls (n = 75) without a fracture history. A conditional-logistic regression analysis addressing the common vitamin D insufficiency/deficiency cutoffs was used. Overweight, obesity, and significant obesity rates were 10.7%, 53.4%, and 35.9%, respectively. Mean (±SD) 25(OH)D was 16.5 ± 6.4 ng/mL. In all, 25(OH)D insufficiency rates (level <20 ng/mL) were 70.5%. Matched cases and controls had similar 25(OH)D insufficiency/deficiency rates (P > .05). Controlling for race and seasonality showed no association between fractures and 25(OH)D insufficiency/deficiency (P > .05). These data suggest that fractures are not associated with low 25(OH)D levels among adolescents whose BMI ≥ 85th percentile.

To study the intake and sources of vitamin D and determinants of serum 25-hydroxyvitamin D (S-25(OH)D) in Finnish adolescents.

We studied 265 adolescents (117 girls) aged 15-17 years attending 8-year examinations of the PANIC Study, assessed diet using food records and other lifestyle factors by questionnaires, and analyzed S-25(OH)D by chemiluminescence immunoassay and determinants of S-25(OH)D using multivariate linear regression.

Mean (standard deviation) of total vitamin D intake from food and supplements was 19.2 (13.1) µg/d, and that of dietary vitamin D intake was 9.9 (5.4) µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 45% of daily intake. Altogether, 29% of the adolescents used no vitamin D supplements and 25% did not meet the recommended total vitamin D intake of 10 µg/d. Mean (standard deviation) of S-25(OH)D was 62.0 (18.8) nmol/l, and S-25(OH)D was < 50 nmol/l in 29.5% of the adolescents. Vitamin D intake from supplements was the main determinant of S-25(OH)D (β = 0.465, p < 0.001), followed by consumption of milk products (β = 0.251, p < 0.001), consumption of meat products (β = 0.179, p = 0.002), travels to sunny countries (β = 0.178, p = 0.002), and average daylight time (β = 0.162, p = 0.004).

Most of the adolescents had vitamin D intake at the recommended level, although a fourth did not meet the recommended total vitamin D intake of 10 µg/d and almost a third had S-25(OH)D < 50 nmol/l. More attention should be paid to the sufficient intake of vitamin D in adolescents who do not use vitamin D supplements or fortified milk products.

ClinicalTrials.gov: NCT01803776, registered March 3, 2013.

Serum alkaline phosphatase (ALP) and its isoenzymes reflect bone metabolism: ALP increases the ratio of inorganic phosphate to pyrophosphate systemically and facilitates mineralization as well as reduces extracellular pyrophosphate concentration, an inhibitor of mineral formation. On the contrary, low ALP activity is associated with reduction of bone turnover. ALP includes four isoenzymes depending on the site of tissue expression: intestinal ALP, placental ALP, germ cell ALP and tissue nonspecific ALP or liver/bone/kidney ALP. The bone isoenzyme (B-ALP) is involved in bone calcification and is a marker of bone turnover as a result of osteoblastic activity. ALP and its isoenzymes are crucial in the diagnostic process of all the forms of rickets.The most common cause of rickets is vitamin D nutritional deficiency. The aim of this review is to update on the role played by ALP serum concentrations as a relevant marker in thediagnosis and treatment of rickets. Indeed, the diagnosis of rickets is based on its clinical, radiological and laboratory characteristics. An elevated ALP level is one of the markers for the diagnosis of rickets in children, though it is also associated with bone formation process. ALP is also useful for the differentiation between rickets and other disorders that can mimic rickets because of their clinical and laboratory characteristics, and, together with other biochemical markers, is crucial for the differential diagnosis of the different forms of rickets. Age, severity and duration of rickets may also modulate ALP elevation. Finally, ALP measurements are useful in clinical and therapeutic follow-up.