Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Vitamin D status and determinants in Indian children and adolescents: a multicentre study.

Studies performed on Indian children to assess vitamin-D status have been on small sample sizes, limited to specific geographical locations and used non-standard methods to measure 25(OH)D3. This multicentre study assessed 25(OH)D3 concentrations from dried blood spots (DBS) in 5-18-year-old Indian children and adolescents using a standardized protocol and identified factors contributing towards vitamin D deficiency. Cross-sectional, observational school-based study was conducted by multi-stage stratified random sampling. A city and nearby village were selected from 6 Indian states covering wide geographical areas. Demography, anthropometry, body-composition, dietary-intakes and DBS samples were collected. 25(OH)D3 was assessed from DBS using Liquid chromatography with tandem-mass spectrometry. Vitamin-D status was assessed in 2500 children; with additional data collected on a subset (n = 669) to assess predictors. Mean vitamin-D concentration was 45.8 ± 23.9 nmol/L, 36.8% of subjects had sufficient vitamin-D (> 50 nmol/L); rural subjects and boys had higher concentrations (p < 0.05). On regression analysis, younger age, female-gender, overweight and urban residence significantly contributed to deficiency. More than half the Indian children/adolescents were vitamin-D deficient or insufficient. Our study reinforces vitamin-D deficiency as a major public health problem and the need for supplementation, food fortification and educating the population as initiatives required to improve sufficiency status.

Assessment of Bone Density by DXA in Poorly Controlled Children With ß-Thalassemia: Correction for Hepatic Iron Overload by Manual Analysis.

INTRODUCTION: Beta thalassemia major (BTM) is characterized by anemia and iron overload, especially with inadequate chelation therapy. Dual energy x-ray absorptiometry software (DXA) may misanalyse bone measurements due to iron deposition in organs such as the liver. Our objective was to study difference between the posterior-anterior spine measurements of bone mineral content (BMC), area (BA) and density (BMD) in poorly chelated beta thalassemia patients with and without inclusion of the liver in the DXA analysis. METHODS: We studied hemoglobin and serum ferritin concentrations in 208 patients with BTM (children n = 177, young adults n = 31). Posteroanterior spine measurements BMC, BA and areal BMD were performed using a GE iDXA. Using the tissue point typing feature (EnCore software, version 16), analysis was carried out including and excluding (manually) the iron overloaded liver. Machine generated Z-scores of L1-L4 BMD were used for analysis. RESULTS: The mean age of the study group was 12.9 ± 5.4 yr. Mean hemoglobin and serum ferritin concentrations were 8.0 ± 1.7 g/dl and 2256.9 ± 1978.0 ng/ml, respectively. The mean BMC, BA, and aBMD at the lumbar spine were 23.2 ± 11.4 g, 29.9 ± 8.5 cm2 and 0.736 ± 0.173 g/cm2 respectively with inclusion of liver that is standard machine analysis. After the liver was excluded from the analysis, the mean BMC, BA, and aBMD were 23.9 ± 11.6 g, 30.0 ± 8.6 cm2 and 0.757 ±0.173 g/cm2, respectively and the BMC and aBMD were significantly greater (p < 0.05). Mean BMD Z-score was -1.5 ± 1.2, which significantly (p < 0.05) improved to -1.3 ± 1.2 after exclusion of the liver from the analysis. CONCLUSION: In poorly chelated patients with thalassemia, inclusion of the iron-overloaded liver in the tissue analysis may exaggerate the deficit in bone parameters. Iron overloaded tissues need to be manually excluded during analysis of the PA spine.

Cost-Effectiveness of Vitamin D Supplementation in Pregnant Woman and Young Children in Preventing Rickets: A Modeling Study.

Background: Literature on the cost of management of rickets and cost-effectiveness of vitamin D supplementation in preventing rickets is lacking. Methods: This study considered the cost-effectiveness of providing free vitamin D supplementation to pregnant women and children <4 years of age with varying degrees of skin pigmentation to prevent rickets in children. Estimates for the prevalence of rickets were calculated using all cases of rickets diagnosed in Central Manchester, UK and census data from the region. Cost of management of rickets were calculated using National Health Service, UK tariffs. The efficacy of vitamin D supplementation was based on a similar programme implemented in Birmingham. Quality of life was assessed using utility estimates derived from a systematic literature review. In this analysis the intervention was considered cost-effective if the incremental cost-effectiveness ratio (ICER) is below the National Institute for Health and Care Excellence, UK cost-effectiveness threshold of £20,000 per Quality-adjusted life year (QALY). Results: Fifty-seven patients (26 dark, 29 medium and 2 light skin tones) were managed for rickets and associated complications over 4-years. Rickets has an estimated annual incidence of 29·75 per 100,000 children <4 years of age. In the dark skin tone population vitamin D supplementation proved to be cost saving. In a medium skin tone population and light skin tone populations the ICER was £19,295 per QALY and £404,047 per QALY, respectively. Conclusion: Our study demonstrates that a vitamin D supplementation to prevent rickets is cost effective in dark and medium skin tone populations.

Occurrence of infections in schoolchildren subsequent to supplementation with vitamin D-calcium or zinc: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. MATERIALS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

Nutritional rickets under 16 years: UK surveillance results.

OBJECTIVE: The UK national incidence of nutritional rickets is unknown. We aimed to describe the incidence, presentation and clinical management of children under 16 years with nutritional rickets in the UK presenting to secondary care. METHODS: Prospective data were collected monthly between March 2015 and March 2017 from 3500 consultant paediatricians using British Paediatric Surveillance Unit methodology. Clinicians completed online clinical questionnaires for cases fitting the surveillance case definition. RESULTS: 125 cases met the case definition, an annual incidence of 0.48 (95% CI 0.37 to 0.62) per 100 000 children under 16 years. 116 children were under 5 years (annual incidence of 1.39 (95% CI 1.05 to 1.81) per 100 000. Boys (70%) were significantly more affected than girls (30%) (OR 2.17, 95% CI 1.25 to 3.78). The majority were of Black (43%) or South Asian (38%) ethnicity. 77.6% of children were not taking vitamin D supplements despite being eligible. Complications included delayed gross motor development (26.4%), fractures (9.6%), hypocalcaemic seizures (8%) and dilated cardiomyopathy (3%). Two children died (1.6%). In eight cases, rickets was confirmed radiologically and biochemically [raised serum alkaline phosphatase (ALP) and parathyroid hormone (PTH) levels ] but were excluded from the incidence analysis for not meeting the case definition of 25-hydroxyvitamin D of <25 nmol/L. CONCLUSION: The incidence of nutritional rickets in the UK is lower than expected. Serious complications and unexpected deaths, particularly in Black and South Asian children under 5 years, occurred. Both vitamin D deficiency and dietary calcium deficiency are role players in pathogenesis. Uptake of vitamin D supplementation remains low.

Paradoxical Response of Parathyroid Hormone to Vitamin D-Calcium Supplementation in Indian Children.

OBJECTIVES: To investigate the effect of oral vitamin D-calcium supplementation on serum intact parathyroid hormone (PTH), calcium, phosphorous, and alkaline phosphatase (ALK-P) concentrations in children with habitually low calcium intakes. STUDY DESIGN: In this follow-up study to a randomized controlled trial that aimed to assess the effect of vitamin D-calcium supplementation on immunity, data related to dietary intake, anthropometry, and biochemistry [serum 25(OH)D and bone profile] were collected from 178 children-79 in the vitamin D group and 99 in the non-vitamin D group. RESULTS: Dietary calcium to phosphorus intake ratio was 0.4:1. Baseline serum 25(OH)D concentration was 58.2 ± 10.9 nmol/L; 66% children were vitamin D sufficient and none deficient. After supplementation, vitamin D group, compared with the non-vitamin D group, had significantly (P < .05) greater 25(OH)D (83.9 ± 30.1 nmol/L vs 58.3 ± 15.7 nmol/L), significantly greater PTH (6.7 ± 3.6 pmol/L vs 5.5 ± 3.2 pmol/L), and positive correlation (rs = 0.24) between serum 25(OH)D and PTH (vs negative correlation [rs = -0.1] in non-vitamin D group). Mean concentrations of serum bone measures in the vitamin D group were calcium (2.2 ± 0.1 mmol/L), phosphorus (1.7 ± 0.2 mmol/L), and ALK-P (178.7 ± 40.7 IU/L). At follow-up, 1-year post-supplementation, in the vitamin D group, PTH concentrations continued to remain high (but not significantly different from levels at 6 months), with low normal serum calcium, high normal phosphate, and ALK-P in reference range. CONCLUSIONS: In children who are vitamin D sufficient but with habitually low dietary calcium intake, vitamin D-calcium supplementation paradoxically and significantly increased serum PTH concentrations with no apparent effect on other bone biochemistry. Chronic low dietary calcium to phosphorus ratio is likely to have caused this paradoxical response.

Randomized Control Trial Assessing Impact of Increased Sunlight Exposure versus Vitamin D Supplementation on Lipid Profile in Indian Vitamin D Deficient Men.

BACKGROUND: Despite abundance of sunshine in India, Vitamin D deficiency is common and therefore there is an increasing trend toward taking Vitamin D supplements either as prescription medicine or as a nutritional supplement. Studies have suggested that duration of sun exposure may influence serum lipid profile. OBJECTIVES: To study the effect of increased sunlight exposure versus Vitamin D supplementation on Vitamin D status and lipid profile in individuals with Vitamin D deficiency (25-hydroxyvitamin-D [25OHD] <50 nmol/L). DESIGN: A prospective, randomized open-label trial was carried out in apparently healthy Indian men (40-60 years). Based on 25OHD concentrations, individuals were divided into control (>50 nmol/L, n = 50) and intervention (<50 nmol/L, n = 100) groups. Individuals from intervention group were randomly allocated to two groups; either "increased sunlight exposure group" (n = 50, received at least 20 min sunlight exposure to forearms and face between 11 a.m. and 3 p.m. over and above their current exposure) or "cholecalciferol supplement group" (n = 50, received oral cholecalciferol 1000 IU/day). RESULTS: Significant increase in 25OHD concentrations was seen in both intervention groups (P < 0.01). Significant decrease in total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), and low-density-lipoprotein cholesterol (LDL-C) was seen in individuals with increased sunlight exposure (P < 0.05). Cholecalciferol supplement group showed a significant increase in TC and HDL-C (P < 0.05) and insignificant increase in LDL-C. CONCLUSIONS: Increase in Vitamin D concentrations through sunlight exposure significantly reduced TC, LDL-C, and HDL-C concentrations, and cholecalciferol supplementation increased TC and HDL-C concentrations.

Assessing the population impact of low rates of vitamin D supplementation on type 1 diabetes using a new statistical method.

Vitamin D supplementation for all children <5 is recommended by the UK Department of Health for its skeletal effects. Vitamin D is also linked with a number of extra-skeletal effects; one of them being protection against type 1 diabetes. With a rapid increase in the incidence of type 1 diabetes and the associated costs, measures of curtailing the rapid increase of type 1 diabetes are needed. In this review, we look at type 1 diabetes using a statistical method (PIN-ER-t) and published data in an attempt to quantify the impact on the population of babies born in 2012 of increasing vitamin D supplementation rates. Calculations show that for the population of 729,674 babies born in England and Wales in 2012, 374 cases of type 1 diabetes (out of 1357 total predicted) could be prevented over 18 years if all were supplemented with vitamin D. This could lead to savings in excess of £62 million for the cohort. This piece of work adds to the argument for studying the potential link between vitamin D supplementation and type 1 diabetes further.

A Cross-Sectional Study of Postpartum Changes in Bone Status in Indian Mothers.

BACKGROUND: Bone turnover is high during lactation. However, studies on bone status of Indian urban mothers are scarce. Hence, the objective was to conduct a cross-sectional study on the lactation-related changes in bone health status of Indian mothers postpartum using Dual X-ray Absorptiometry (DXA) at 3 time points: within a week of delivery, at 1- and 3-years postpartum. We also explored the association of dietary calcium intake, physical activity, serum vitamin D status, and dietary traditional food supplements (Dietary Food supplements) with bone health. METHODS: A cross-sectional study was conducted; 300 full-term, healthy primiparous women (28.6 ± 3.4 year) were randomly selected and categorized into 3 groups: 128 mothers within 7 days of delivery (Group A), 88 with 1-year-old children (B), and 84 with 3-year-old children (C). Anthropometry, lactation history, physical activity, diet, biochemical tests (vitamin D, parathyroid hormone), body composition, areal bone mineral density (a-BMD) at total body (TB), AP spine (APS), and dual neck femur (DF) were assessed by DXA (GE-Lunar DPX). RESULTS: Significantly higher APS-BMD (mean ± SD) was observed in Group C (1.107 ± 0.098 g/cm(2)) than that in A (1.045 ± 0.131 g/cm(2)) (p < 0.05). When adjusted for breastfeeding practices, mean (±standard error) APS-BMD was lowest in women in Group A (1.024 ± 0.013 g/cm(2)), but was higher at 1-year (1.079 ± 0.02 g/cm(2)) and at 3-years postpartum (1.111 ± 0.019 g/cm(2)), though differences were significant only between groups A and C (p < 0.05). Most mothers from all 3 groups consumed inadequate amount of nutrients except dietary fat and showed low physical activity. Multiple regression analysis indicated that dietary calcium, moderate physical activity, serum vitamin D, and consumption of dietary food supplements were not significant predictors of APS-BMD (p > 0.1). CONCLUSION: Prevalence of nutrient and vitamin D deficiencies, low physical activity, and poor sunlight exposure were major concerns in Indian lactating mothers; improvement in bone mass at APS was observed at 3-years which was most likely due to physiologic changes.

Changes in body composition of Indian lactating women: a longitudinal study.

BACKGROUND AND OBJECTIVES: Lactation places enormous demands on maternal bone mineral homeostasis. Indian middle class women (MSC) consume energy dense food supplements to meet these demands post-partum (PP) along with restricted physical activity (PA). Effects of these changes on body composition (BC) of PP women have not been studied. To examine longitudinal changes in: a) bone mineral density (BMD) at total body (TB), AP-spine (APS) and dual femur neck regions (DF) b) BC by body weight, lean mass, fat mass using dual energy X-ray absorptiometry (DXA) at baseline, 6-months and 1-year in urban MSC women. METHODS AND STUDY DESIGN: 76-primi-parous (28±3.2 yrs) randomly selected PP women (<7-days) were studied; 70 reassessed at 6- months and 42 1-yr PP. Data on anthropometry, BC, BMD at TB, APS and DF by DXA collected (baseline, 6- months, 1-yr PP). RESULTS: Weight, waist and body mass index (BMI) decreased both at 6-month and 1-yr PP with respect to baseline (p<0.05). BC changes showed increase in android fat % at 1-yr by 10% over baseline (p<0.05). BMD with initial decline at 6-months (-2.8%, -2.3% and -2.3% respectively) recovered partially by 1-yr (+2.5% +1.2% and +4.8% respectively) at DF and TB with complete recovery at APS (p<0.05). CONCLUSION: These urban relatively sedentary MSC women consumed fat rich food PP with higher android fat retention and partial recovery of BMD at DF and TB at 1-year. Modifications in activity and dietary nutrient intakes may be necessary to prevent cardiovascular and bone health related risks.

Enhanced effect of zinc and calcium supplementation on bone status in growth hormone-deficient children treated with growth hormone: a pilot randomized controlled trial.

Reduced bone mineral content in growth hormone-deficient children (GHD) has been reported. Calcium, zinc, and vitamin D play an important role in bone formation. Hence, the aim of this pilot randomized controlled study was to evaluate the effect of calcium, vitamin D, and zinc supplementation in prepubertal GHD children treated with GH on bone health parameters. After 1 year of treatment with GH (20 mg/m(2)/week), 31 GHD (mean age 8.7 ± 2.8 years, 18 boys) prepubertal children were randomised to receive calcium (500 mg/day) and vitamin D (60,000 IU/3 months) [Group A] or a similar supplement of calcium, vitamin D, and zinc (as per Indian Recommended Allowance) [Group B] along with GH therapy for the next 12 months. The two groups were similar in anthropometric and body composition parameters at baseline (p > 0.1). After 1 year of GH therapy, height-adjusted % gain was similar in both groups, 48 % in bone mineral content (BMC) and 45 % in bone area (BA). Height-adjusted % increase in BMC was significantly (p < 0.05) higher in the second year than in the first in both the groups. This % increase in BMC and BA was greater in Group B (51 and 36 % respectively) than in Group A (49 and 34 %), although marginally (p < 0.05). Supplementation of calcium and vitamin D along with GH therapy in GHD Indian children has the potential for enhancing bone mass accrual; this effect was further enhanced through the addition of zinc supplement.