Impact of Childhood Obesity on Bone Metabolism.

Objective To examine the relationship between the concentration of 25-hydroxy vitamin D3[25-(OH)D3] in the serum and the body mass, the severity of obesity, body mass index(BMI), blood lipid, and their predicting role in obesity children. Methods The study recruited 244 subjects, who see the doctor in Wuxi Maternal and Child Health Hospital, Childhood Nutrition Outpatient from Jul.2011 to Feb.2013.The intake dose of vitamin D each day was investigated, and weight, height, BMI, concentration of 25-(OH)D3 in serum, and microelement were also mea-sured.In addition, lipid metabolism of 38 cases with obesity over 3 years old was determined. Results 1.The serum 25-(OH)D3 concentration of obese children was (68.31±23.06) nmol/L.The concentration of 25-(OH)D3 was lowest in the group of obese children over 36 months of age[(55.03±15.18) nmol/L].2.The concentration of 25-(OH)D3 in the group of obese and overweight children was far lower than that of the children in the normal group(F=4.739, P<0.05).3.The concentrations of 25-(OH)D3 in the severely obese children was significantly lower than that of the mild and moderate obesity children(F=9.711, P<0.05).4.There were significantly inverse associations of serum 25-(OH)D3 with weight, weight and height percentage, BMI(r=-0.365, -0.237, -0.175, all P<0.001).5.There were significantly inverse associations between the concentration of 25-(OH)D3 in serum with weight, triglyceride in obese children more than 3 years old(r=0.476, -0.324, all P<0.05). Conclusions The decreasing level of 25-hydroxy vitamin D3 in the serum was associated with obesity.The cause of it might be the increase of the obese adipose tissue, vitamin D getting trapped in fat cells, and all these factors can lead to a less serum vitamin D levels.The vitamin D consumption of obese children is higher than that of normal children, and should supply more vitamin D to reach normal 25-(OH) D3 level. Key words: Serum 25-hydroxy vitamin D3 concentration; Child; Obesity

Objective The aim of this study was to assess vitamin D status in obese school-aged children and to correlate vitamin D levels with other clinical and laboratory investigations. Background Obesity and vitamin D deficiency have been classified as epidemics throughout the world; many studies have shown that vitamin D status and fat mass are inversely correlated. Patient and methods This study was carried out on 80 children ranging in age from 6 to 18 years divided according to BMI into two groups: an obese group [40 children (12 boys and 28 girls)] and a control group [40 apparently healthy children (17 boys and 23 girls)]. All children were subjected to a full assessment of history, clinical examination, and laboratory investigations including complete blood picture, qualitative C-reactive protein (CRP), fasting lipid profile (serum cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein), serum calcium (total), phosphorus, alkaline phosphatase, and serum 25(OH)-vitamin D. Results Our results showed that obese children had significantly higher values than the controls on all anthropometric measurements except the upper/lower segment ratio; they had significantly higher blood pressure, lower levels of hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and higher levels of all parameters of the lipid profile except high-density lipoprotein, which was lower. Positive CRP was detected in 80% of the children in the obese group, with 100% negative CRP in the control group. They had significantly lower 25(OH)-vitamin D than the controls; vitamin D deficiency was detected in 52.5% of obese children, and 47.5% of these children had vitamin D insufficiency. However, 52.5% of the controls had 25(OH)-vitamin D insufficiency. A significantly positive correlation was detected between triceps skinfold thickness and fasting serum cholesterol in the obese group. Conclusion Obese children are prone to hypertension, dyslipidemia, microcytic hypochromic anemia, inflammatory process, and vitamin D deficiency; apparently healthy children may have undiagnosed vitamin D insufficiency.

Objective To investigate the effects of vitamin D deficiency on bone turnover and bone mineral density in patients with a blunted PTH response as compared to patients with vitamin D deficiency and secondary hyperparathyroidism.Method A total of 542 postmenopausal women [mean age (64.0 ± 10.8) years] were evaluated by assessing serum calcium,phosphate,alkaline phosphatase,25-hydroxy vitamin D (25-OHD),PTH,bone turnover markers such as osteocalcin,C-terminal telopeptide of type Ⅰ collagen(CTX) and procollagen type Ⅰ amino-terminal propeptide(PINP),and bone mineral density of lumber spine,total hip and femur neck etc.Result (1) The prevalence of vitamin D deficiency in this cohort was 24％.Mean 25-OHD varied across seasons (P =0.023) ; women who paid visits during winter and spring yielded significantly lower levels of 25-OHD than those who had their visit during the fall (P =0.012 and P =0.039).Serum PTH and bone turnover markers did not vary by season.(2) All subjects could be divided into four groups occording to their serum 25-OHD and PTH levels.Group 1:25-OHD＜ 10 ng/ml and PTH ≥ 65 pg/ml (7.0％),group 2:25-OHD ＜ 10 ng/ml and PTH ＜ 65 pg/ml (17.0％),group 3:25-OHD ≥ 10 ng/ml and PTH＜65 pg/ml (73.6％),group 4:25-OHD ≥ 10 ng/ml and PTH ≥ 65 pg/ml (2.4％).Blunted PTH response was found in 70.8％ of patients with vitamin D deficiency.Patients with vitamin D deficiency and a blunted PTH response were characterized by a lowered serum calcium,a reduction in bone turnover (serum CTX and serum osteocalcin),but protection in bone density as compared to those with vitamin D deficiency and secondary hyperparathyroidism.(3) As for spine bone mineral density,the significant independent predictors were body mass index(r2 =0.370,P＜0.01),age(r2 =-0.158,P＜0.01),PTH(r2 =-0.121,P＜0.05),and serum CTX(r2 =-0.118,P＜0.05).For femoral neck bone mineral density,the significant independent predictors were years since menopause(r2 =-0.201,P＜O.01) and body mass index(r2 =0.139,P＜0.05).And for hip bone mineral density,the significant independent predictors were age (r2 =-0.239,P＜0.01) and body mass index (r2 =0.239,P＜0.01).There was little correlation between 25-OHD and bone mineral density.Conclusion This study identifies a high prevalence of vitamin D deficiency in healthy postmenopausal women in shanghai,and a distinct group of patients with vitamin D deficiency and a blunted PTH response as shown by disruption in calcium homeostasis but protection against PTH-mediated bone loss.Compared with hip,spine bone mineral density is more sensitive to higher serum PTH and higher bone turnover. Key words: 25-hydroxy vitamin D; Serum parathyroid hormone; Hyperparathyroidism; Bone turnover; Bone mineral density

Osteoporosis as a worldwide problem is discussed in the present review and the question of improving peak bone mass to reduce the risk of osteoporosis and osteoporotic fracture is addressed. The available evidence points to pre-puberty and puberty as the most opportune periods for intervention, but the potential for achievable increments in bone mass is shown to be small compared with the overwhelming influence of heredity, body composition and hormonal factors on bone. Lean body mass appears to be positively correlated with bone mass, while black-white racial differences in bone mass appear to be related to greater lean mass and lower bone turnover rate in blacks. Within races, twin and parent-offspring models have suggested that 46-80 % of the variance in bone mineral density can be explained by inherited factors; however, the mechanism of the genetic influence on bone density remains poorly understood. Moderate regular exercise seems to maintain bone mass while more vigorous regular exercise increases it in children and young adults. Ca intake has been found to be positively associated with bone mass in many but not all studies, possibly because of a ceiling at about 1300-1500 mg/d for young people. Other nutritional variables, including vitamin D, have been little investigated in relation to childhood and adolescent bone mass. The influence of milk as a source of highly bioavailable Ca and other nutrients has also been less frequently investigated, which is of concern given the cessation of school milk programmes in Western countries over the last three decades. Intervention studies to improve bone health in young people have mainly been based on Ca milk or exercise. The evidence points to the benefits to bone of such interventions, particularly when commenced pre-puberty, and it seems that daily consumption of 200-300 ml milk/d by children and adolescents has no adverse side effects. The benefits to bone are almost universally shown to be lost fairly rapidly after Ca or exercise intervention ceases; there is therefore no justification in terms of bone health for short-term interventions of this nature. The question of withdrawal of milk supplementation has undergone very little examination. Further, very little evidence is available on the effects of long-term interventions of any sort on bone health. Nevertheless, the data obtained so far permit the suggestion that promotion of Ca intake (e.g. at the higher level of current recommendations) and exercise commencing in the pre-pubertal period should be adopted as policy now.

Introduction: Deficiency of vitamin D is pandemic and has been associated with a wide variety of disease states such as cardiovascular disease risk factors and impaired glucose homeostasis and are more common in overweight and obese children. Both endocrine and metabolic disorders occur with obesity and it has been suggested that obesity is a risk factor for vitamin D deficiency. The inverse association between higher body fat and lower vitamin D levels has been attributed to sequestration of the fat soluble vitamins within the plentiful adipose tissue. Aim and Objective: This study aims to determine the status of vitamin D levels in overweight and obese adolescent children and to compare them with age and sex matched healthy controls. Materials and Methods: This observational study was conducted in the Department of Biochemistry in collaboration with Department of Pediatrics, Pt. B.D. Sharma, PGIMS, Rohtak. Twenty-five overweight and obese adolescents based on BMI were recruited in study group (Group II) and twenty-five age and sex matched healthy controls were included in group I (Control group). Study samples were drawn and serum vitamin D levels were analyzed by radioimmunoassay. Results: Out of 25 cases 12(48%) were overweight and 13(52%) were obese adolescents. Mean BMI in group I was 17.36±3.67 kg/m2 and in group II was 31.90±1.01 kg/m2. 14 (56%) had vitamin D levels

An influence of the 3-months weight-reduction programme on vitamin D concentration in obese prepubertal children was evaluated. The programme consisted of dietary and physical activity modifications and behaviour therapy including individual psychological care for the child and its family. The recommended daily intake from low-energy diet was 1200–1400 kcal/day. Vitamin D intake was lower in obese children before and during therapy in comparison to the controls and recommended intake. Hypovitaminosis D in obese children corresponded to decreased vitamin D intake and was more prevalent during fall/winter than spring/summer. Analysis of diet and measurements of the serum vitamin D concentration in obese children during weight-reduction therapy may be useful for monitoring of this vitamin status and for modifications of diet or supplementation. Further longitudinal studies are necessary to study the relationship between obesity, weight loss and vitamin D in prepubertal children.

Vitamin D plays a pivotal role in the pathogenesis and treatment of renal bone disease. Vitamin D levels decline in the early phase of renal failure; however, through a compensatory mechanism parathyroid hormone (PTH) stimulates the production of calcitriol to return it to normal circulating concentrations. Nevertheless, resistance to calcitriol is observed and may be related to the decreased presence of the heterodimeric, DNA-binding partner for the vitamin D receptor protein. In end-stage kidney disease (ESKD) the circulating levels of calcitriol are invariably low. The indications of vitamin D therapy are the replacement of the missing hormone versus suppression of hyperparathyroidism requiring daily low-dose oral versus intermittent pulse or oral administration. However, this therapy must be accompanied by careful patient monitoring to avoid hypercalcemia and low bone turnover. Low bone turnover is not merely a histologic entity, but a clinical condition associated with high risk of extraosseous calcifications, in particular in the cardiovascular system, leading to increased morbidity. Thus, determination of bone turnover in patients with ESKD is essential. Bone biopsy is the gold standard to assess bone turnover, however, it is not always available and nephrologists rely on PTH levels. The intact PTH assay measures PTH (1-84) and large C-PTH fragments, which may antagonize the PTH (1-84) effects on bone. An assay that measures exclusively PTH (1-84) has recently become available and a calculated PTH (1-84) /C-PTH fragment ratio has been shown to be the best predictor of bone turnover in patients with ESKD not treated with vitamin D or with other medications known to affect bone metabolism. 22-Oxacalcitriol is a vitamin D analogue that could control serum PTH concentrations without deleterious effects on bone.

Obesity, induced by unhealthy lifestyle choices, could be involved in the development of chronic diseases like type 2 diabete. Obesity is largely due to the imbalance of energy intake and expenditure, therefore we have put more emphasis on the amount of macronutrients including carbohydrates, fats and proteins as dietary therapy for obesity and related-conditions. On the other hand, several studies revealed obese or diabetic patients were more likely to have micronutrient deficiencies such as vitamins and minerals. Besides the effects on bone metabolism, vitamin D and calcium might contribute to metabolic disorder accompanied by obesity. However, it has not been concluded supplementation of these two nutrients has a benefit in obese or diabetic individuals. Further studies are needed.

Vitamin D is finally converted into the active form in the kidney, which is regulated and affected by several factors such as calcium . phosphate balance, parathyroid hormone (PTH), calcitonin and fibroblast growth factor 23 (FGF23). Activated vitamin D works as hormone and engages in calcium . bone metabolism. In chronic kidney disease, the active form can be decreased and therefore, renal osteodystrophy can be lead as consequences of mineral metabolism abnormality and unregulated PTH production/secretion as increased activity of the parathyroid glands (2HPT). Moreover, because chronic kidney disease (CKD)-associated abnormal states in above are detrimental to CKD patients not only in terms of renal osteodystrophy, but progress of cardiovascular disease and mortality. Therefore new concept is proposed as chronic kidney disease-mineral bone disorder (CKD-MBD).

Vitamin D plays a pivotal role in the regulation of bone metabolism, essentially through its effects on calcium and phosphate absorption. Although major targets of vitamin D action are skeletal system and mineral metabolism, vitamin D receptor is ubiquitously expressed in many tissues. Accumulating evidence suggests a possible involvement of vitamin D in the regulation of blood sugar and blood pressure in addition to its effects on bone and mineral metabolism.

Epidemic of Childhood Obesity: Implications for Kidney Disease

The discovery of vitamin D receptor (VDR) in many tissues opens a new era in vitamin D (VD) research, far beyond the mineral homeostasis and bone metabolism. The enormous data on the epidemic VD deficiency focused the attention on its role for prevention of numerous diseases, such as cancer, diabetes etc. The calcitriol molecular mode of action ranges from immediate nongenomic responses to long-term genomic effects, linked to cell proliferation, differentiation and survival. In vitro and in vivo studies demonstrate the antiproliferative role of VD. In accordance with this data we have studied prostate cancer patients and determined that VD deficiency was negatively correlated with tumor aggressiveness. The immunomodulatory role of VD has been recognized for many years. Recently, multiple studies have been focused on the role of the VD status on immune response to infection and on the novel effects of VD related to gut microbiota. Studying the effect of VD status in hepatitis C viral infection patients we found VD deficiency correlating with the viral load, liver fibrosis and the effect of antiviral therapy. In an effort to examine the role of VD on gut microbiota, we studied the relation between VD status and the frequency and severity of diarrhea syndrome in toddlers. In all studied children VD deficiency was related to a more severe diarrhea syndrome. By its noncalcitropic effects VD regulates the function of numerous organs and systems including endocrine pancreas, liver, and fat tissue. It is supposed that subclinical VD deficiency may result in insulin resistance, beta-cell dysfunction, diabetes and metabolic syndrome. Our study on normal weight and obese pre-pubertal children revealed VD deficiency in more than 50% of them, correlating with poor metabolic status. In relation to the noncalcemic effects of VD it might be supposed that defining and correcting the VD status of risky groups may reduce the risk of development of socially significant diseases, such as cancer, metabolic and immunodeficient diseases .

Vitamin D is indispensable for bone health and calcium metabolism, and decreased action of vitamin D causes various abnormalities in bone metabolism. Severe vitamin D deficiency causes osteomalacia/rickets. Even milder vitamin D insufficiency could still be harmful for bone health via secondary hyperparathyroidism and bone loss, and could also lead to increased risk of falling. Osteomalacia/rickets associated with impaired vitamin D action should be treated by either native or active vitamin D3, depending on its etiology. As for osteoporosis, vitamin D repletion is important to adequate therapeutic effects of anti-resorptives. As a monotherapy, eldecalcitol, active vitamin D3 analogue, has been shown to increase bone mineral density and to decrease the incidence of vertebral fractures with significantly greater efficacy compared to active vitamin D3.

Vitamin D deficiency in the past was defined by the clinical recognition of nutritional rickets, a disease nearly eradicated by vitamin D fortification. Today, the definition of vitamin D deficiency is controversial, and is based on serum concentrations of 25-hydroxyvitamin D (25(OH)D), a marker of storage rather than of function. The level of 25(OH)D that is optimal for bone health may differ from that required for non-skeletal benefits. Observational studies suggest wide-ranging effects of vitamin D status on metabolic, immunologic, infectious, cardiovascular, neoplastic, and degenerative disorders. There is likely wide individual variation in the functional implications of a given level of 25(OH)D. As randomized controlled trials confirm the benefits of vitamin D in non-skeletal diseases, the recommended intake of vitamin D and optimal 25(OH)D concentration may need to be adjusted to account for these outcomes. The future will bring an individualized approach to assessing vitamin D status and needs. Even when the factors known to influence 25(OH)D concentrations are accounted for, most of the individual variation of 25(OH)D values is difficult to explain. This variation is partially explained by genotypic variants of the vitamin D binding protein, vitamin D receptor, and the hydroxylase enzymes of the vitamin D metabolic pathway. With more widespread use of genome-wide analysis, it may be possible to personalize an individual’s vitamin D requirement, particularly in view of other disease risk factors. Measurement of the physiological effects of vitamin D that relate to bone metabolism, the immune system, or other effectors of disease could allow tailoring of the dose of vitamin D to attain maximal physiological benefit. Additional markers of the functional response to vitamin D at the individual level may be available in the future. Vitamin D has exciting potential, and a flurry of research activity is now underway to explore its potential benefits.

Objective To investigate the effects of secondary hypoparathyroidism on bone metabolism and health management in patients with differentiated thyroid carcinoma(DTC). Methods Sixty patients with DTC who underwent total or subtotal thyroidectomy from January 2017 to May 2018 were enrolled. Among them, 30 patients had secondary hypoparathyroidism and hypocalcemia(hypothyroidism), while the other 30 patients had normal parathyroid function(control group). These two groups of patients were routinely examined for their parathyroid hormone(PTH), vitamin D, serum calcium, serum phosphorus, alkaline phosphatase(ALP), free triiodothyronine(FT3), free thyroxine(FT4), and thyroid stimulating hormone(TSH) at 1, 6, and 12 months after surgery and to determine dual-energy X-ray bone mineral density(BMD) and health-management-related indicators. PTH, vitamin D, serum calcium, serum phosphorus, and ALP in the parathyroid group were tested by conducting a paired t-test, and the indicators for the parathyroid and control groups(FT3, FT4, TSH, and L2 to L4, neck of femoral, femur trochanter, Ward’ s triangle BMD value) were compared by conducting an independent sample t-test. Results 1. A statistically significant difference in PTH, serum calcium, and serum phosphorus was observed among patients with hypothyroidism at 1 and 6 months after surgery, 6 months after surgery, and 12 months after surgery(PTH: t= –2.467, –2.753, P=0.021, 0.033; serum calcium: t=–2.941, –3.652, P=0.007, 0.002; serum phosphorus: t=4.550, 4.167, P=0.000, 0.004), but no significant difference was observed in terms of vitamin D and ALP(vitamin D: t=2.153, 1.965, P=0.062, 0.074; ALP: t=1.970, 1.672, P=0.061, 0.066); 2. At 12 months after surgery, the BMD of the neck of femoral decreased in the parathyroid group, showing a statistically significant difference from the control group(t=1.08, P=0.002). At 1, 6, and 12 months after surgery, the patients with hypothyroidism showed no significant differences from the control group in terms of thyroid function level(FT3, FT4, and TSH), lumbar vertebrae(L2 to L4), Ward’s triangle, and femur trochanter BMD(t=0.606 to 1.82, all P>0.05). 3. After taking calcium and vitamin D, the clinical symptoms of hypocalcemia in patients with hypothyroidism were significantly improved. Twelve months after surgery, hand and foot numbness and muscle spasms accounted for 6.67% of the symptoms, and after taking calcium and vitamin D, the medication compliance of the patients decreased to 80%. Conclusions 1.The BMD of neck of femoral in patients with hypothyroidism decreased at 12 months after surgery, and the BMD of lumbar vertebrae(L2~L4), Ward’s triangle and femur trochanter was not significant; 2.Most patients with parathyroid hypofunction showed clinical manifestations of hypocalcemia after DTC, and their symptoms were significantly relieved after the calcium and active vitamin D treatment. However, the medication compliance of these patients gradually declined. Therefore, health education and management should be further strengthened. Key words: Differentiated thyroid carcinoma; Hypoparathyroidism; Bone density; Health management