Anna Challa

Vitamin D: A Necessity for Children and Adolescents in Greece

Children and adolescents with the high bone turnover comprise a high risk population for vitamin D insufficiency. A sample of 178 clinically healthy children aged 3 to 18 years who came from public schools and lived in North West of Greece participated in the study. They were grouped into three age groups (I: 3–10, II: 11–14 and III: 15–18 years of age). Blood samples were taken during winter and summer months for determining calciotropic hormones, calcium, phosphate and biochemical markers of bone synthesis.A high percentage (47%) of the subjects aged 15–18 years was found to have 25OHD <10 ng/ml in winter but much less (13–14%) of the younger ages (13–14 years), while in the summer they were all >10 ng/ml. The prevalence was even higher in the girls of the older group accompanied by lower Pi concentrations again in winter (win:1.19±0.03, sum:1.93±0.03 mmol/l, p < 0.001). The 24,25(OH)2D levels were changing in parallel to 25OHD, but again in the older subjects, during winter, they were by 2/3 lower than the summer ones (0.73±0.10 vs. 2.41±0.20 ng/ml, p < 0.001). No significant differences were found between seasons and groups in the 1,25(OH)2D levels. The biochemical markers of bone synthesis, osteocalcin (OC) and total alkaline phosphatase (ALP), were found significantly lower in the girls of the older group both in winter and summer respectively.Even in a sunny country like Greece the adolescents living in an urban area are in high risk for vitamin D deficiency during winter. Supplementation with vitamin D of milk, of popular beverages and perhaps some foods would be of help.

Novel roles of vitamin D in disease: What is new in 2011?

Vitamin D is a steroid molecule, mainly produced in the skin that regulates the expression of a large number of genes. Until recently its main known role was to control bone metabolism and calcium and phosphorus homeostasis. During the last 2 decades it has been realized that vitamin D deficiency, which is really common worldwide, could be a new risk factor for many chronic diseases, such as the metabolic syndrome and its components, the whole spectrum of cardiovascular diseases, several auto-immune conditions, and many types of cancer as well as all-cause mortality. Except for the great number of epidemiological studies that support the above presumptions, vitamin D receptors (VDRs) have been identified in many tissues and cells. The effect of vitamin D supplementation remains controversial and the need for more persuasive study outcomes is intense.

Cortisol Secretion in Stressed Babies during the Neonatal Period

The present study investigates the developmental pattern of serum cortisol secretion in sick fullterm and preterm neonates in comparison to that of normal babies over the first 30 days of life. Four groups of babies (15 in each group) were studied sequentially during the first 4 weeks of life. Serial venous blood samples were drawn at 08.00, 14.00, 20.00 and 02.00 h from each baby. The higher cortisol levels (p < 0.001) observed in sick preterm and full-term neonates, when compared to their respective controls, suggest an appropriate response to stress. Fullterm and preterm babies with no problem were found to have a free running rhythm in serum cortisol levels during the first 4 weeks of life.

Prothrombotic State, Cardiovascular, and Metabolic Syndrome Risk Factors in Prepubertal Children Born Large for Gestational Age

OBJECTIVE To evaluate metabolic syndrome and cardiovascular disease risk factors in prepubertal children born large for gestational age (LGA) to nondiabetic, nonobese mothers. RESEARCH DESIGN AND METHODS At 6–7 years of age, the comparison of various factors was made between 31 LGA and 34 appropriate-for-gestational-age (AGA) children: fibrinogen, antithrombin III, protein C and S, fasting insulin, glucose, homeostasis assessment model of insulin resistance (HOMA-IR) index, adiponectin, leptin, visfatin, IGF-1, IGF-binding protein (IGFBP)-1, IGFBP-3, lipids, and the genetic factors V Leiden G1691A mutation, prothrombin 20210A/G polymorphism, and mutation in the enzyme 5,10-methylenetetrahydrofolate-reductase gene (MTHFR-C677T). RESULTS LGA children had higher levels of leptin (P < 0.01), fasting insulin (P < 0.01), and HOMA-IR (P < 0.01), but lower IGFBP-3 (P = 0.0001), fibrinogen (P = 0.0001), and lipoprotein(a) (P < 0.001) than AGA children. Significantly more LGA children were homozygous for the MTHFR-C677T mutation (P = 0.0016). CONCLUSIONS Being born LGA to nondiabetic, nonobese mothers is associated with diverse effects on cardiometabolic risk factors at prepuberty.

Vitamin D metabolites (25‐hydroxyvitamin D, 24,25‐dihydroxyvitamin D and 1,25‐dihydroxyvitamin D) and osteocalcin in β‐thalassaemia

Serum levels of the vitamin D metabolites 25‐hydroxyvitamin D, 24,25‐dihydroxyvitamin D, and 1,25‐dihydroxyvitamin D. and of osteocalcin. C‐tenninal parathyroid hormone and other biochemical indices related to bone metabolism, were determined in two groups of patients with β‐thalassaemia aged 5–10 years (summer 7.8 ± 0.4 years, mean ± SEM. and winter 7.7 ± 0.4 years, group A, n= 15) and 11–23 years (16.6 ± 0.9 and 15.7 ± 0.9 years in summer and winter, respectively, group B, n= 22). Emphasis was given to populations of school and adolescent ages and to the seasons of summer and winter when vitamin D status demonstrates the widest extremes. The mean serum levels of 25‐hydroxyvitamin D in patients aged 5–10 years did not differ from those of controls during both seasons studied. In contrast, in the age group 11–23 years these levels were found to be lower in patients than in controls both in winter (10.6 ± 0.9ng/ml vs 15.0 ± 2.0ng/ml, p < 0.05) and summer (20.2 ± 2.1 ng/ml vs 27.1 ± 2.0ng/ml, p < 0.05). The serum concentrations of 24,25‐dihydroxyvitamin D were lower in the thalassaemic patients than in controls in both age groups and both seasons. In the patients under 10 years of age the mean values of this metabolite in winter were 1.06 ± 0.17 ng/ml vs 1.68 ± 0.20 ng/ml in the respective controls (p < 0.05), and in summer 1.44 ± 0.11 ng/ml vs 2.35 ± 0.36 ng/ml in controls (p < 0.05). In the group of patients aged 11–23 years, the mean levels of 24,25‐dihydroxyvitamin D were in winter 0.65 ± 0.12 ng/ml vs 1.12 ± 0.19 ng/ml (p < 0.05) in controls and in summer 1.34 ± 0.12 ng/ml vs 1.84 ± 0.20 ng/ml (p < 0.05). The 1,25‐dihydroxyvitamin D concentrations in both thalassaemic patient groups were significantly no different from those in the respective control groups. Serum osteocalcin, C‐terminal parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase levels in the patients studied were not significantly different from those in controls, except for calcium and phosphate in the older group. In the older group of thalassaemic patients, serum calcium was lower than in the controls (2.26 ± 0.03 vs 2.37 ± 0.03 mmol/1, p < 0.05) in summer and serum phosphate higher than in the controls in winter (1.47 ± 0.05 mmol/1 vs 1.27 ± 0.06 mmol/1. p < 0.05).

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

Osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL) and fibroblast growth factor-23 (FGF-23) play a central role in renal osteodystrophy. We evaluated OPG/RANKL and FGF-23 levels in 51 children with chronic kidney disease (CKD) [n = 26 stage 3 or 4 (CKD3–4) and n = 25 stage 5 (CKD5)] and 61 controls. Any possible association with intact parathyroid hormone (iPTH) and bone turnover markers was also investigated. The OPG levels were lower in the CKD3–4 group (p < 0.001) and higher in the CKD5 group (p < 0.01) than in the controls, while RANKL levels did not differ. The FGF-23 levels were higher in both patient groups (p < 0.0001), while the levels of phosphate and iPTH were higher only in the CKD5 group (p < 0.0001). There were independent positive correlations between OPG and RANKL (β = 0.297, p < 0.01) and FGF-23 (β = 0.352, p < 0.05) and a negative correlation with the bone resorption marker TRAP5b (β = −0.519, p < 0.001). OPG was positively correlated with iPTH (R = 0.391, p < 0.01). An independent positive correlation between FGF-23 and phosphate (β = 0.368, p < 0.05) or iPTH (β = 0.812, p < 0.0001) was noted. In conclusion, we found that higher OPG levels in patients with CKD stage 5 correlated with the levels of RANKL, FGF-23, iPTH, and TRAP5b. These findings may reflect a compensatory mechanism to the negative balance of bone turnover. High FGF-23 levels in early CKD stages may indicate the need for intervention to manage serum phosphate (Pi) levels.

Growth factors and adipocytokines in prepubertal children born small for gestational age: relation to insulin resistance.

OBJECTIVE The aim of this study was to test whether being born small for gestational age (SGA) has an impact on adiponectin and leptin levels and the IGF system in relation to insulin sensitivity, taking into consideration the severity of growth restriction. RESEARCH DESIGN AND METHODS Serum levels of adiponectin, leptin, fasting glucose, fasting insulin (IF), the homeostasis model assessment insulin resistance index (HOMA-IR), IGF-1, free IGF-1, IGF-binding protein (IGFBP)-1 and -3, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were evaluated in 57 children at age 4–10 years. Of these, 32 had been born appropriate size for gestational age (AGA) and 25 SGA (14 in the <3rd percentile and 11 in the 3rd–10th percentile). RESULTS The SGA 3rd–10th percentile children were already insulin resistant at prepubertal age (IF 39.6 ± 16.8 vs. 27 ± 12 pmol/l, P < 0.01, and HOMA-IR 1.4 ± 0.6 vs. 0.95 ± 0.42 in SGA vs. AGA children, P < 0.05). Their IGF-1 and IGFBP-3 concentrations were significantly lower than those in AGA children (160.4 ± 66.2 vs. 207 ± 66.8 μg/l, P < 0.05 and 2.3 ± 0.4 vs. 3.51 ± 1.21 mg/l in SGA vs. AGA children, P < 0.01). The SGA <3rd percentile children had higher adiponectin (15.6 ± 5.7 mg/l, P < 0.05) and IGFBP-1 levels (113.5 ± 33.9 μg/l, P < 0.05) than AGA children (11.3 ± 6.6 mg/l and 90.8 ± 24.2 μg/l, respectively) and lower IGF-1 and IGFBP-3 concentrations (162.6 ± 68.4 μg/l, P < 0.05 and 2.4 ± 0.7 mg/l, P < 0.01). They also had significantly lower waist circumference (P < 0.05). Leptin levels did not differ among groups, but an inverse correlation with IGFBP-1 (r = −0.55, P < 0.01) was found in the pooled SGA group. CONCLUSIONS Intrauterine growth restriction appears to affect the IGF axis at prepubertal age, and its severity plays a role in insulin sensitivity.

Vitamin D and Stroke: Promise for Prevention and Better Outcome

The role of vitamin D (VitD) has recently been expanded beyond bone homeostasis and regulation of calcium levels. VitD deficiency has been proposed as a new risk factor for cardiovascular disease, including stroke. Low 25(OH)VitD levels are very common among post-stroke patients, probably due to their limited mobility and decreased sunlight exposure along with a higher prevalence of malnutrition, and they have been associated with previous and incident cerebrovascular events. Contributing mechanisms have been linked to the association of VitD deficiency with the presence of hypertension, diabetes mellitus and atherosclerosis. Moreover, there is experimental evidence demonstrating that VitD exerts neuroprotective effects, such as stimulation of neurotrophic factors, quenching of oxidative hyperactivity and regulation of neuronal death, as well as antithrombotic properties. It is plausible that VitD supplementation could be a beneficial intervention for the prevention and/or treatment of cerebrovascular disease possibly by decreasing the aforementioned cerebrovascular risk factors and simultaneously by improving neurologic and cognitive functions, thereby reducing falls and fractures in post-stroke patients. However, study results are still conflicting and data from large, randomized clinical trials are needed to clarify these speculations.

Effects of Intranasal Salmon Calcitonin in Juvenile Idiopathic Arthritis: An Observational Study

The aim of this study was to follow the changes in bone mineral density (BMD) and biochemical markers of bone turnover in 10 children (7.5-17.5 years of age) with severe juvenile idiopathic arthritis (JIA), during a 3-year therapy with salmon calcitonin (100 IU/day 2 months on and 2 off for a year and 200 IU/day for 2 years) and calcium (500 mg/day). All patients were functional classes III and IV and were measured at yearly intervals with a dual photon absorptiometer at the lumbar spine. The changes observed were 7.2-9.5% per year for BMD and 2.0-6.0% for volumetric bone mineral density (BMDvol). The bone resorption markers showed significant decreases after a years treatment (Pyr/Cr from 175+/-15 to 108+/-15 nm/mm, P < 0.001, Pyr-D/Cr from 24.3+/-3.5 to 13.3+/-1.9 nm/mm, P < 0.05, and OHPr/Cr from 57.4+/-11 to 35.1+/-8.4 microg/mg) and smaller changes thereafter. No significant changes were observed in the bone formation markers of osteocalcin and alkaline phosphatase. Serum iPTH, the vitamin D metabolites, and calcium concentrations fluctuated within normal, while calcium excretion increased from 0.3+/-0.1 to 1.9+/-0.4 mg/kg/24 hours, P < 0.001. In conclusion, the present study, despite its limitations of not being placebo controlled, shows possible beneficial effects of intranasal calcitonin on bone resorption and pain relief in JIA patients.

The relationship of vitamin D with non-traditional risk factors for cardiovascular disease in subjects with metabolic syndrome

Introduction Several studies implicate an inverse relationship between 25-hydroxy vitamin D (25(OH)Vit D) serum levels and metabolic syndrome (MetS). We sought to investigate a possible relationship between 25(OH)Vit D and emerging risk factors associated with MetS, such as small dense low-density lipoprotein cholesterol (sdLDL-C) concentration, lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and high-sensitivity C-reactive protein (hsCRP) levels. Material and methods We studied 110 consecutive otherwise healthy individuals. Of these, 52 were diagnosed with MetS and 58 who did not meet the MetS criteria served as controls. Low-density lipoprotein (LDL) subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA2 activity was determined in total plasma by the trichloroacetic acid precipitation procedure. Serum 25(OH)Vit D was determined quantitatively by an enzyme immunoassay method. Results Metabolic syndrome subjects had significantly lower 25(OH)Vit D levels (11.8 [0.6-48.3] ng/ml; 29.5 [1.5-120.75] nmol/l) compared with controls (17.2 [4.8-62.4] ng/ml; 43 [12-156] nmol/l, p = 0.027). Univariate regression analysis showed that 25(OH)Vit D concentration was inversely related to triglycerides (r= − 0.416, p = 0.003) and sdLDL-C (r= − 0.305, p = 0.004). There was no association of 25(OH)Vit D with waist circumference, blood pressure, high-density lipoprotein cholesterol (HDL-C), fasting glucose, Lp-PLA2 and hsCRP. In multivariate regression analysis the relationship between 25(OH)Vit D and sdLDL-C became insignificant when triglycerides were included in the model. Conclusions Subjects with MetS exhibit lower 25(OH)Vit D serum levels compared with non-MetS individuals. Low 25(OH)Vit D is associated with higher sdLDL-C levels possibly through elevated triglycerides. No association between 25(OH)Vit D and Lp-PLA2 or hsCRP was found.