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.

Impact of Adolescent Pregnancy on Bone Density in Underprivileged Pre-Menopausal Indian Women.

High prevalence (31.5%) of adolescent pregnancies (AP) have been reported in India. Reports suggest that pregnancy during adolescence may have deleterious effects on peak bone mass. Very few studies have described the long-term effects of a history of AP on bone mass. The objective of this study was to compare bone mineral density (BMD) and bone geometry of premenopausal women with first childbirth during adolescence (i.e., before age of 19 years) or after 20 years. A cross-sectional study was conducted in 242 women (age 28.0-54.5 years) from Pune, India (November, 2015 to November, 2017). Women were divided into 2-groups: Group-1: women-who had 1st-pregnancy and childbirth before 19 years of age (AP n = 131) and Group-2: women-who had 1st pregnancy after 20 years of age (non-AP n = 111). Demographic data, anthropometric measurements, and biochemical tests were performed using standard protocols. Physical activity and nutrient intakes were recorded using validated questionnaires. Areal BMD and bone geometry were measured using Dual-Energy-Absorptiometry-DXA (Lunar-iDXA, GE Healthcare) and peripheral-quantitative-computed-tomography-pQCT (XCT2000, Stratec Inc.). Mean age of the study group was 37 ± 4.6 years; in women from group-1 mean age at first delivery was 16.9 ± 1.6 years as against 22.6 ± 3.1 years in group-2. Both groups were similar in body mass index and socioeconomic status. pQCT measured radial diaphyseal cortical thickness (1.97 ± 0.3 mm vs 1.88 ± 0.3 mm resp., p = 0.016, periosteal circumference (38.0 ± 3.6 mm vs 36.7 ± 2.5 mm, resp. p = 0.016), total bone area (114.3 ± 24.8 mm2 vs 108.7 ± 14.7 mm2 resp. p = 0.026) and stress-strain index (SSI = 217 ± 75 vs 201 ± 40 mm3 resp. p = 0.042) were significantly higher in group-1 than group-2. After adjusting for anthropometric and lifestyle parameters, pQCT measured cortical thickness (1.98 ± 0.03 mm in group-1, 1.87 ± 0.03 mm group-2, p = 0.01, mean ± SE) and iDXA derived aBMD at forearm were still significantly higher (0.599 ± 0.006 g/cm3 vs 0.580 ± 0.006 g/cm3, p = 0.023) in Group-1. Our data suggest that women with a history of adolescent pregnancy had better bone geometry and higher aBMD at radius in later years. We speculate that early exposure to pregnancy resulted in higher aBMD at the radius and induced changes at radial diaphysis with bones becoming thicker and wider among these women.

Increased prevalence of fractures in inadequately transfused and chelated Indian children and young adults with beta thalassemia major.

INTRODUCTION: In patients with beta thalassemia major, inadequate transfusion and chelation may compromise bone health and increase risk of fractures. The objective of this study was to describe the prevalence of fractures in Indian inadequately transfused and chelated children, adolescents and young adults with beta thalassemia major. METHODS: We studied 179 patients with beta thalassemia (3.6-28.3 years; 105 boys). Medical, transfusion, chelation and fracture history were recorded. Vertebral fracture assessment (VFA) was performed using lateral spine images acquired using the GE Lunar iDXA (Wisconsin, MD). Fractures were classified according to an adapted semi-quantitative method. RESULTS: History of non-traumatic long bone fractures was observed in 21% patients (n = 37); there were significantly greater (p < 0.05) number of males (n = 30) than females (n = 15). The 21% fracture prevalence in the present study is higher than the reported fractures of 9% in healthy Indian children and adolescents. The prevalence of vertebral fractures was 4.5% (n = 8) in the study group. Of those with fractures, four patients had both long bone and vertebral fractures, and (any, long bone or vertebral fractures) sixteen patients had more than 1 fracture; eleven patients had 2 fractures, four patients had 3 fractures and one patient had 5 fractures. Thus, in 179 patients, there were a total of 68 single fractures which translates to 307 fractures per 10,000 patient years. CONCLUSION: This study found increased prevalence of non-traumatic long bone and vertebral fractures in children and adolescents with thalassemia major.

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.

DXA and pQCT derived parameters in Indian children with beta thalassemia major - A case controlled study.

Children with beta thalassemia major (BTM) are known to have reduced bone mass which increases incidence of non-traumatic fractures. Few studies have assessed prevalence of fractures and bone health in underprivileged children with BTM. Our objectives were to 1) determine prevalence of fractures in underprivileged Indian children with BTM, 2) assess size corrected bone density and bone geometry using Dual x-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT) in these children and healthy controls 3) determine predictors of fractures in children with BTM 4) compare differences in bone density between children with BMT with and without fractures. Bone mineral content and areal bone mineral density (aBMD) of lumbar spine and whole body and vertebral fracture assessment (VFA) was performed by DXA in 334 children (3-18 years, 167 BTM + 167 controls). Volumetric BMD (vBMD) and bone geometry were assessed by pQCT (subset, 70 BTM, 70 healthy) at distal radius. Children with BTM had higher prevalence of vertebral and long bone fractures (p < 0.05). DXA aBMD was lower in children with BTM (p < 0.05), whereas, lumbar spine bone mineral apparent density (LSBMAD) was higher (p > 0.05). Children with BTM had lower total distal radial vBMD, cortical vBMD and strength strain index (SSI) at 66% site whereas, distal radial trabecular vBMD at 4% was higher (p < 0.05). On height adjustment, children with BTM had lower muscle area and cortical thickness and higher marrow area (p < 0.05) at 66% site. Age, body size, total body less head (TBLH) aBMD and strength strain index (SSI) were important predictors of fractures in children with BTM. Thus, children with BTM had higher prevalence of non-traumatic fractures. Despite lower areal and volumetric densities, they had higher LSBMAD and trabecular densities which may be attributed to erythroid hyperplasia and iron deposition due to inadequate transfusion and chelation. As LSBMAD is raised in these children, it is unlikely to identify BTM subjects at risk of fracture; VFA thus maybe useful in identifying asymptomatic vertebral fractures.

To study impact of treatment with Rosuvastatin versus Atorvastatin on 25 hydroxy Vitamin D concentrations among adult Indian men- a randomized control trial.

BACKGROUND: Dyslipidemias are on the rise and are increasingly being treated with statins. As the metabolism of cholecalciferol and cholesterol are interrelated, reduction in cholesterol synthesis by statins is likely to affect Vitamin D status. OBJECTIVES: (1) The aim is to study the effect of treatment with statins (Atorvastatin/Rosuvastatin) on 25-hydroxy-Vitamin-D (25OHD) among newly detected subjects with dyslipidemia for 6 months (2) To study the impact of 25OHD concentrations on the efficacy of statin treatment. MATERIALS AND METHODS: This was a prospective, balanced randomized (1:1), open-label, parallel-group study, in apparently healthy Indian adult men (south Asian, 40-60 years). At baseline, serum lipids and 25OHD concentrations were measured. Based on the Adult Treatment Panel III guidelines, subjects were divided as per lipid concentrations into controls (who did not require statin treatment) and intervention (who required statin treatment) groups. Random allocation of subjects was done in two groups for receiving intervention for 6 months: Atorvastatin group (n = 52, received Atorvastatin) or Rosuvastatin group (n = 52, received Rosuvastatin). Lipids and 25OHD concentrations were measured at the end line. RESULTS: Atorvastatin group presented significant reduction (P < 0.05) in 25OHD, total cholesterol (TC) and low-density-lipoprotein-cholesterol (LDL-C) concentrations at the end line. In the Rosuvastatin group, significant drop in TC, LDL-C and high-density lipoprotein cholesterol (concentrations (P < 0.05) was observed, while 25OHD concentrations showed no significant change. Mean 25OHD concentrations were significantly correlated with a reduction in LDL-C concentrations in Atorvastatin group. CONCLUSIONS: Treatment with Atorvastatin resulted in a reduction in 25OHD concentrations; further, its efficacy in reducing LDL-C concentrations was related to the 25OHD concentrations.

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.

The international X-linked hypophosphataemia (XLH) registry (NCT03193476): rationale for and description of an international, observational study.

BACKGROUND: X-linked hypophosphataemia (XLH) is a rare, hereditary, progressive and lifelong phosphate wasting disorder characterised by pathological elevations in fibroblast growth factor (FGF) 23 concentration and activity; XLH has an incidence of approximately 1 in 20-25,000 individuals. Excess FGF23 activity leads to increased phosphate excretion in the kidneys - mediated by downregulation of renal tubular phosphate transporters - and reduced phosphate absorption in the intestines - due to impaired vitamin D activation. This results in impaired bone growth and mineralisation, short and disproportionate stature, leg bowing, musculoskeletal pain, spontaneous dental abscesses, rickets, and osteomalacia. The spectrum of manifestations differs between paediatric and adult patients. Those involved in the treatment of this condition face many challenges, including a lack of robust natural history and demographic data. This multicentre, international, rare-disease patient registry (XLH Registry) was established to address the paucity of data in XLH and to help inform future clinical practice. RESULTS: The XLH Registry collects standard diagnostic and monitoring practice data, including (where applicable) diagnosis and disease progression history, treatment regimens and family history; the protocol does not mandate any interventions or clinical assessments. The XLH Registry aims to recruit 1200 paediatric and adult patients with XLH over 10 years, and several data analyses and peer-reviewed publications are expected to be generated throughout this period. A post-authorisation safety study for Bburosumab, for which the registry Sponsor is the marketing authorisation holder, will be nested as a sub-study within the XLH Registry via a subsequent protocol amendment. CONCLUSION: The data collected within this rare-disease patient registry will be utilised to synthesise real-world evidence to inform the management of XLH, to improve the quality of life and standard of care of patients living with this rare debilitating disease.

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.

Perceived fatigue in children and young adults with neurofibromatosis type 1.

AIM: This study describes the prevalence and severity of perceived fatigue in a young neurofibromatosis type 1 (NF1) population. METHODS: Ethical approval was obtained and NF1 affected Individuals aged 2-18 years from the Manchester's NF1 clinic invited along with any unaffected siblings. The PedsQL Multidimensional Fatigue Scale Parental and child report was used. This validated measure explores cognitive, physical and sleep/rest domains on a 0-100 scale. Higher scores indicate less fatigue. Fatigue scores in affected children were compared to unaffected siblings after adjusting for age, sex and Index of Multiple Deprivation and with published population standards using z-scores. RESULTS: A total of 286 families were invited and 75 affected and 16 siblings participated. There were significant differences between NF1 and controls in the aggregated fatigue core (child report 55 ± 19 vs. 75 (14), P < 0.001; parent 54 ± 20 vs. 73 ± 18, P = 0.001) and the three sub-domains: cognitive (child 48 ± 27 vs. 75 ± 23, P < 0.001), physical (child 59 ± 19 vs. 82 ± 14, P < 0.001) and sleep/rest (child 59 ± 19 vs. 71 ± 15, P = 0.018). Similar differences were seen when compared with published controls (aggregated child z-score -1.9 ± 1.4, P < 0.001; parent -3.2 ± 1.8, P < 0.001). Prevalence of severe fatigue indicated by scores <2 standard deviation below published means for healthy controls were also higher for children with NF on both parent and child reports. Agreement between child and parent reports were limited as is frequently seen in the literature. CONCLUSION: This study suggests that children with NF1 are affected by perceived fatigue when compared with healthy children who do not have NF1.

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.

Muscle and bone parameters in underprivileged Indian children and adolescents with T1DM.

BACKGROUND: The incidence of Type 1 diabetes mellitus (T1DM) is increasing and sarcopenia and osteoporosis have been reported to be associated with long standing diabetes. There is scarcity of data on bone health status of children with T1DM. Our aim was to assess bone health parameters [by Dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT)] and muscle strength (by hand grip) in underprivileged Indian children with T1DM. MATERIAL AND METHODS: A cross sectional, observational study was conducted in underprivileged children with diabetes attending the out patient clinic for T1DM at a tertiary care hospital. Children with T1DM with disease duration more than 1 year were included in the study. Age and gender matched controls were also enrolled. Data on age, gender, disease duration, anthropometric parameters and HbA1c were collected. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (Lunar iDXA) and peripheral quantitative computed tomography (pQCT, Stratec XCT 2000) and muscle strength by handgrip. Data were analysed using SPSS 25.0. RESULTS: 251 children with T1DM and 250 age gender matched controls were studied. Mean age of T1DM children was 10.8 ± 4.3yrs (controls 10.3 ± 3.6). Mean HbA1C was 9.7 ± 2.1%. The total body less head areal BMD (TBLH aBMD) and lumbar spine bone mineral apparent density (LSBMAD) Z-scores were significantly lower in children with T1DM (-1.5 ± 1.3, -1.3 ± 1.6 respectively) as compared to controls (-0.5 ± 1.3, -0.64 ± 1.5 respectively) (p < 0.05 for both). Z-scores for trabecular and total density (vBMD) were significantly lower in patients with T1DM (-0.7 ± 1.0, -0.7 ± 1.0 respectively) than controls (-0.15 ± 1.2, -0.31 ± 1.1), (p < 0.05) and trabecular density was lower at distal radius with increasing disease duration. Hand-grip strength Z-score was lower in children with T1DM (-3.0 ± 0.5) as compared to controls (-2.8 ± 0.5). Trabecular density and HbA1C concentrations were negatively correlated (R = -0.18, p < 0.05) as was muscle area and HbA1C concentrations (R = -0.17, p < 0.05,). CONCLUSION: Bone and muscle health were affected in children with poorly controlled T1DM. With increasing disease duration, attention is required for optimising musculoskeletal health.

FGF23 and its role in X-linked hypophosphatemia-related morbidity.

BACKGROUND: X-linked hypophosphatemia (XLH) is an inherited disease of phosphate metabolism in which inactivating mutations of the Phosphate Regulating Endopeptidase Homolog, X-Linked (PHEX) gene lead to local and systemic effects including impaired growth, rickets, osteomalacia, bone abnormalities, bone pain, spontaneous dental abscesses, hearing difficulties, enthesopathy, osteoarthritis, and muscular dysfunction. Patients with XLH present with elevated levels of fibroblast growth factor 23 (FGF23), which is thought to mediate many of the aforementioned manifestations of the disease. Elevated FGF23 has also been observed in many other diseases of hypophosphatemia, and a range of animal models have been developed to study these diseases, yet the role of FGF23 in the pathophysiology of XLH is incompletely understood. METHODS: The role of FGF23 in the pathophysiology of XLH is here reviewed by describing what is known about phenotypes associated with various PHEX mutations, animal models of XLH, and non-nutritional diseases of hypophosphatemia, and by presenting molecular pathways that have been proposed to contribute to manifestations of XLH. RESULTS: The pathophysiology of XLH is complex, involving a range of molecular pathways that variously contribute to different manifestations of the disease. Hypophosphatemia due to elevated FGF23 is the most obvious contributor, however localised fluctuations in tissue non-specific alkaline phosphatase (TNAP), pyrophosphate, calcitriol and direct effects of FGF23 have been observed to be associated with certain manifestations. CONCLUSIONS: By describing what is known about these pathways, this review highlights key areas for future research that would contribute to the understanding and clinical treatment of non-nutritional diseases of hypophosphatemia, particularly XLH.

Duration of Casual Sunlight Exposure Necessary for Adequate Vitamin D Status in Indian Men.

OBJECTIVES: To investigate the duration of casual sunlight ultraviolet-B (UVB) exposure required to maintain optimal Vitamin D status (25-hydroxyvitamin-D [25(OH)D]) >50 nmol/L in urban Indian men, using polysulfone (PSU) dosimeters and a sunlight exposure questionnaire. METHODS: In healthy men (aged 40-60 years) from Pune (18.52° N, 73.86° E), India, serum 25(OH)D was measured using enzyme-linked immunosorbent assay. Sunlight exposure was assessed using PSU dosimeter and by questionnaire. RESULTS: Of 160 men (48.3 ± 5.6 years), 26.8% were deficient and 40.6% had insufficient Vitamin D concentrations. A hyperbolic function for the relationship between PSU measured sunlight exposure in standard erythema dose (SED) and serum 25(OH)D concentrations (r = 0.87, P < 0.01) revealed that daily exposure of 1 SED was sufficient to maintain serum 25(OH)D concentrations over 50 nmol/L. The curve plateaued around 5 SED (80 nmol/L) and extrapolation of the curve (>5 SED) did not increase 25(OH)D concentrations above 90 nmol/L. Receiver operating curve analysis confirmed that 1 SED-UV exposure was sufficient to maintain 25(OH)D concentrations over 50 nmol/L. Based on the questionnaire data, >1 h of midday casual sunlight exposure was required to maintain serum 25(OH)D concentrations above 50 nmol/L. Duration of sunlight exposure assessed by questionnaire and PSU dosimeter showed a significant correlation (r = 0.517, P < 0.01). CONCLUSION: In urban Indian men, >1 h of casual midday sunlight exposure daily was required to maintain serum 25(OH)D concentrations above 50 nmol/L, and >2 h of casual sunlight exposure was needed to maintain 25(OH)D concentrations above 75 nmol/L. Excess sunlight did not increase 25(OH)D linearly. The sunlight exposure questionnaire was validated for use in clinical studies and surveys.

Dietary patterns with special reference to calcium intake in 2-16-year-old Urban Western Indian children.

BACKGROUND: It is important to establish good dietary practices in childhood that promote adequate calcium intake throughout life and reduce the risk of osteoporotic fractures in later life. OBJECTIVES: To assess dietary patterns of 2-16-year-old children with special reference to calcium and suggest strategies and develop recipes suitable to identified patterns to increase dietary calcium intake. METHODS: We studied 220 schoolchildren (2-16 years) around Pune city, India. The study duration was June 2013-July 2014. Height and weight were measured using standard protocols. Dietary intake was assessed by 24-h diet recall on 3 nonconsecutive days. Dietary patterns were derived by cluster analysis in two age groups; children (2-9 years) and adolescents (10-16 years). As per the dietary patterns, calcium-rich recipes were developed. RESULTS: Among children, "rice-pulse" (RP) and "wheat, milk, and milk products" (WM) patterns were observed. Among adolescents, RP, "wheat, milk, and bakery" (WMB), and "mixed food" patterns were observed. Children who consumed "WM" and "WMB" patterns had greater intake of calcium (P < 0.05) than children consuming other dietary patterns. The daily calcium intake of whole group was 53% of the recommended dietary allowance. From this, 30% calcium came from milk. Each serve of the developed recipe provided an average of 254 mg of calcium. CONCLUSION: Majority of children had cereal-pulse-based dietary patterns. By replacing foods from existing dietary patterns with calcium-rich foods, the dietary calcium content may be increased in a sustainable manner.

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.

Interrelationship between serum 25-hydroxyvitamin D3 concentration and lipid profiles in premenopausal Indian women.

CONTEXT: Vitamin D deficiency is prevalent worldwide, and observational studies have associated it with an atherogenic lipid profile. AIM: To determine the interrelationship between Vitamin D and lipid profile in apparently healthy premenopausal Indian women, considering confounding factors such as lifestyle that independently influence lipids. SETTING AND DESIGN: Cross-sectional study. SUBJECTS AND METHODS: One hundred and twenty healthy premenopausal women (20-45 year) were recruited from Gujarat, India. Data were collected on anthropometry, physical activity, sunlight exposure, and diet. Fasting blood samples were collected for the measurement of serum 25-hydroxyvitamin D3 (25[OH]D), parathyroid hormone, and lipid profile. STATISTICAL ANALYSIS: Pearson's correlation coefficient was used to derive correlation between serum 25[OH]D concentrations and serum lipids. RESULTS: Ninety-three percent women showed Vitamin D deficiency (serum 25[OH]D < 20 ng/ml). Serum 25(OH)D concentrations showed significant inverse correlation with total cholesterol (TC) (r = -0.202, P = 0.027), triglycerides (TG) (r = -0.284, P = 0.002), and low-density lipoprotein-cholesterol (LDL-C) (r = -0.184, P = 0.044) and positive correlation with high-density lipoprotein-cholesterol (HDL-C) (r = 0.250, P = 0.006). On dichotomizing the population according to median 25(OH)D concentration (11.1 ng/dl), no significant differences were observed between the groups for anthropometry, sunlight exposure, and lifestyle. Serum lipid profiles were significantly different, above median serum 25(OH)D concentration group showed favorable serum lipids (TC: 179.3 ± 30 vs. 191.8 ± 31.7 mg/dl; TG: 140 ± 39.1 vs. 165.5 ± 53.4 mg/dl; LDL-C: 100 ± 30.2 vs. 112 ± 32 mg/dl; HDL-C: 53 ± 14 vs. 47.6 ± 9.3 mg/dl)(P < 0.05). CONCLUSIONS: This study demonstrates that association of 25(OH)D concentrations with lipid profile even after considering lifestyle factors which independently influence lipids. Intervention trials would be required to prove this association to be causation.

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.