Vitamin D supplementation for improving bone density in vitamin D-deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D-deficient children are unclear. OBJECTIVES: This study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D-deficient individuals. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1-19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. RESULTS: Eleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. CONCLUSIONS: Clinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets). This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772.

Bone status of Indian children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: Low bone mineral density has been reported in children and adolescents with type 1 diabetes (T1DM). The aims of this cross-sectional study were to study growth, serum IGF1 concentrations and bone health parameters assessed by Dual Energy X-ray Absorptiometry (DXA). METHODS: Height was measured and converted to Z scores (HAZ). Serum IGF1 concentrations were measured (ELISA) in a subset. Bone mineral content for total body (less head) (TBBMC) and lumbar spine was measured (n=170, 77 boys, 6-16years old) and converted to Z scores using local normative data. RESULT: Mean age was 11.1±3.8years, disease duration was 2.2±2.5years and HbA1C was 10.1±1.8%. Diabetic children were shorter than reference population (HAZ -0.6±1.1); Z scores for height and total body bone area (TBBA) for height were <-2SD in 12% & 6% respectively. Serum IGF1 Z scores were lower amongst group with longer disease duration (-1.58±1.3 vs -2.63±0.7; P=0.037). Disease duration (ß=-0.180, P=0.000) and metabolic control (HbA1C; ß=-0.096, P=0.042) were negative predictors of HAZ and TBBA for height Z in younger children. Using the Molgaard approach, children with longer disease duration had lower HAZ (-0.31±0.92 vs -1.28±1.11; P=0.000; "short bones") and TBBA for height Z scores (0.12±1.62 vs -0.53±0.94; P=0.044; "slender bones"). Older children (tanner stages 4 and 5) had lower BMC and BA as compared to reference population possibly due to delayed growth spurt. CONCLUSION: Longer duration of diabetes was associated with shorter and slender but appropriately mineralized bones. Small and slender bones in diabetic children may increase risk of fragility fractures in the future. This article is part of a Special Issue entitled "Bone and diabetes".

Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial.

OBJECTIVES: To determine whether (i) supplementation of oral 100,000 iu of vitamin D(3) (cholecalciferol) along with antibiotics will reduce the duration of illness in children with pneumonia; (ii) supplementation will reduce the risk of repeat episodes. METHODS: Double-blind individually randomised placebo-controlled trial in an inner-city hospital in Kabul, of 453 children aged 1-36 months, diagnosed with non-severe or severe pneumonia at the outpatient clinic. Children with rickets, other concurrent severe diseases, very severe pneumonia or wheeze, were excluded. Children were given vitamin D(3) or placebo drops additional to routine pneumonia treatment. RESULTS: Two hundred and twenty-four children received vitamin D(3;) and 229 received placebo. There was no significant difference in the mean number of days to recovery between the vitamin D(3) (4.74 days; SD 2.22) and placebo arms (4.98 days; SD 2.89; P = 0.17). The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention (92/204; 45%) than the placebo group [122/211; (58%; relative risk 0.78; 95% CI 0.64, 0.94; P = 0.01]. Children in the vitamin D(3) group survived longer without experiencing a repeat episode (72 days vs. 59 days; HR 0.71; 95% CI 0.53-0.95; P = 0.02). CONCLUSION: A single high-dose oral vitamin D(3) supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia.

Vitamin D status of socio-economically deprived children in Kabul, Afghanistan.

BACKGROUND: Cultural, environmental, and diet-related factors were postulated to lead to a high prevalence of vitamin D deficiency in Kabul's socioeconomically deprived children under 5 years of age. We investigated the prevalence of plasma 25-hydroxyvitamin D (25-OHD) deficiency in such a group. METHODS: Children between 6 months and up to 5 years of age were randomly sampled in the Chindawal area of Kabul in January 2005. Plasma samples were frozen to below -20 degrees C and 25(OH)D3 concentrations estimated by high-pressure liquid chromatography. RESULTS: For all 107 children tested, the median plasma 25(OH)D concentration was 5 ng/mL with a range of 2-24 ng/mL; 73% had concentrations of < 8 ng/mL; 13 other samples were not analyzed due to insufficiency of plasma, staff, or technical problems. About 35 others approached either did not give consent or blood could not be obtained. CONCLUSIONS: This study was conducted in a high-risk population at a peak season for vitamin D deficiency. We conclude that this population of children living in Kabul to be at great risk of developing vitamin D deficiency, rickets, and other possible immunological effects of deficiency.

UK reference data for the Hologic QDR Discovery dual-energy x ray absorptiometry scanner in healthy children and young adults aged 6-17 years.

BACKGROUND: The use and correct interpretation of bone densitometry measurements in paediatric patients relies on the availability of appropriate reference data. Ideally, such data should be matched for sex, chronological age, height, weight, pubertal development and ethnicity. AIM: To provide UK-specific reference data for the Hologic QDR Discovery dual-energy x ray absorptiometry (DXA) scanners. METHODS: Healthy, Caucasian children aged 5-18 years were recruited from local schools, colleges, general practitioner surgeries and staff from the University of Manchester, Manchester, UK. Suitable participants had DXA measurements taken of the lumbar spine, hip and total body. Sex-specific reference centile curves for bone mineral apparent density (BMAD; spine and femoral neck) are provided, using the approach suggested by Mølgaard et al. to interpret the scans. LMS (lambda, mu, varsigma) tables for calculation of individual standard deviation scores (SDSs) were produced; a weblink is provided to these tables to allow calculation of an individual child's SDSs. RESULTS: The total study population consisted of 442 participants (239 male). The total numbers of scans available for analysis were 431 of the lumbar spine, 426 of the total body and 393 of the proximal femur. Data are provided for clinical interpretation of the spine and femoral neck scans based on BMAD (g/cm3), which reduces the size dependence of DXA areal bone mineral density (g/cm2). The spine and total-body data are also presented for interpretation of results using the approach suggested by Mølgaard et al. CONCLUSIONS: This article provides the first sex-specific and ethnicity-specific reference databases for UK, which should allow the clinician to assess bone mineral density in paediatric patients, measured by the Hologic QDR Discovery DXA scanner.