Kate Ward

Critical windows for nutritional interventions against stunting.

An analysis of early growth patterns in children from 54 resource-poor countries in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score during the first 2 y of life and no recovery until ≥5 y of age. This finding has focused attention on the period −9 to 24 mo as a window of opportunity for interventions against stunting and has garnered considerable political backing for investment targeted at the first 1000 d. These important initiatives should not be undermined, but the objective of this study was to counteract the growing impression that interventions outside of this period cannot be effective. We illustrate our arguments using longitudinal data from the Consortium of Health Oriented Research in Transitioning collaboration (Brazil, Guatemala, India, Philippines, and South Africa) and our own cross-sectional and longitudinal growth data from rural Gambia. We show that substantial height catch-up occurs between 24 mo and midchildhood and again between midchildhood and adulthood, even in the absence of any interventions. Longitudinal growth data from rural Gambia also illustrate that an extended pubertal growth phase allows very considerable height recovery, especially in girls during adolescence. In light of the critical importance of maternal stature to her childrens health, our arguments are a reminder of the importance of the more comprehensive UNICEF/Sub-Committee on Nutrition Through the Life-Cycle approach. In particular, we argue that adolescence represents an additional window of opportunity during which substantial life cycle and intergenerational effects can be accrued. The regulation of such growth is complex and may be affected by nutritional interventions imposed many years previously.

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 (λ, μ, ς) 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.

Quantitative Computer Tomography in Children and Adolescents: The 2013 ISCD Pediatric Official Positions

In 2007, International Society of Clinical Densitometry Pediatric Positions Task Forces reviewed the evidence for the clinical application of peripheral quantitative computed tomography (pQCT) in children and adolescents. At that time, numerous limitations regarding the clinical application of pQCT were identified, although its use as a research modality for investigation of bone strength was highlighted. The present report provides an updated review of evidence for the clinical application of pQCT, as well as additional reviews of whole body QCT scans of the central and peripheral skeletons, and high-resolution pQCT in children. Although these techniques remain in the domain of research, this report summarizes the recent literature and evidence of the clinical applicability and offers general recommendations regarding the use of these modalities in pediatric bone health assessment.

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: The European Male Aging Study (EMAS)

CONTEXT There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover. OBJECTIVE The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men. DESIGN, SETTING, AND PARTICIPANTS Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers. MAIN OUTCOME MEASURE(S) QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured. RESULTS A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels. CONCLUSIONS Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.

Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men

The aim of this study was to determine if single‐nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r2 ≥ 0.8) were selected for RANKL, RANK, and OPG and their 10‐kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome‐wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population‐based study of male aging, the European Male Ageing Study (EMAS). N‐terminal propeptide of type I procollagen (PINP) and C‐terminal cross‐linked telopeptide of type I collagen (CTX‐I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total‐hip areal BMD (BMDa) was measured by dual‐energy X‐ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (β = 1.83, p = .004) and CTX‐I (β = 17.59, p = 4.74 × 10−4), and lower lumbar spine BMDa (β = −0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (β = −1.84, p = .003) and CTX‐I (β = −27.02, p = 6.06 × 10−8) and higher ultrasound BMD at the calcaneus (β = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men.

Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men.

Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations, when compared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men. Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes. Design and Setting: Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included. Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index. Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53–0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP. Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes.

Growth From Birth to Adulthood and Bone Phenotype in Early Old Age: A British Birth Cohort Study

There is growing evidence that early growth influences bone mass in later life but most studies are limited to birth weight and/or early infant growth and dual‐energy X‐ray absorptiometry (DXA) measurements. In a British birth cohort study with prospective measures of lifetime height and weight, we investigated the growth trajectory in relation to bone in males (M) and females (F) at 60 to 64 years old. Outcomes were DXA measures of hip and spine areal bone density (aBMD) (n = 1658) and pQCT measures of distal and diaphyseal radius cross‐sectional area (CSA), strength, and volumetric bone density (vBMD) (n = 1350 of the 1658). Regression models examined percentage change in bone parameters with standardized measures of birth weight, height, and weight. A series of conditional growth models were fitted for height and weight gain (using intervals: birth–2, 2–4, 4–7, 7–15, 15–20, 20–36, and 36–64 years) and height gain (using intervals: 2–4, 4–7, 7–15, and 15–36 years). Birth weight was positively related to bone CSA (M: 1.4%; 95% confidence interval [CI], 0.3%–2.5%; F: 1.3%; 95% CI, 0.3%–2.4% per 1 SD increase in birth weight for diaphyseal CSA) and strength (M: 1.8%; 95% CI, 0.3–3.4; F: 2.0%; 95% CI, 0.5–3.5). No positive associations were found with trabecular, total, or cortical vBMD. One SD change in prepubertal and postpubertal height and weight velocities were associated with between 2% and 5% greater bone CSA and strength. Height gain in later years was negatively associated with trabecular vBMD. Weight gain velocity during the adult years was positively associated with up to 4% greater trabecular and total BMD, and 4% greater aBMD at hip and spine. In a cohort born in the early post‐war period, higher birth weight, gaining weight and height faster than others, particularly through the prepubertal and postpubertal periods, was positively related to bone strength, mostly through greater bone CSA, at 60 to 64 years.

Bone mass, body composition and vitamin D status of ARV-naïve, urban, black South African women with HIV infection, stratified by CD4 count

SummaryThis is the first report examining vitamin D status and bone mass in African women with HIV infection using dual-energy X-ray absorptiometry (DXA) with an appropriate HIV-negative control group. Unlike previous publications, it demonstrates no difference in bone mineral density (BMD) or vitamin D status in HIV-positive patients, at different disease stages, vs. HIV-negative subjects.IntroductionLow bone mass and poor vitamin D status have been reported among HIV-positive patients; suggesting HIV or its treatment may increase the risk of osteoporosis, a particular concern for women in countries with high HIV prevalence such as South Africa. We describe bone mass and vitamin D status in urban premenopausal South African women, who were HIV positive but not on antiretroviral therapy (ARV).MethodsThis study is a cross-sectional measurement of BMD and body composition by DXA and vitamin D status by serum 25-hydroxyvitamin D (25(OH)D) concentration. Subjects were recruited into three groups: HIV negative (n = 98) and HIV positive with preserved CD4 cell count (non-ARV; n = 74) or low CD4 cell counts prior to ARV initiation (pre-ARV; n = 75).ResultsThe mean (standard deviation (SD)) age of women was 32.1 (7.2) years. Mean CD4 (SD) counts (×106/l) were 412 (91) and 161 (69) in non-ARV and pre-ARV groups (p < 0.0001). Pre-ARV women were significantly lighter and had lower mean BMI than the other two groups (p < 0.002). The pre-ARV group also had significantly less fat and lean mass compared with non-ARV and HIV-negative subjects (p ≤ 0.05). After full adjustment, there were no significant differences in BMD at any site (p > 0.05) between the groups, nor was vitamin D status significantly different between groups (p > 0.05); the mean (SD) cohort 25(OH)D being 60 (18) nmol/l.ConclusionContrary to previous studies, these HIV-positive women did not have lower BMD or 25(OH)D concentrations than HIV-negative controls, despite the pre-ARV group being lighter with lower BMI.

Endocrine determinants of incident sarcopenia in middle‐aged and elderly European men

In men, the long‐term consequences of low serum levels of sex steroids, vitamin D metabolites, and insulin‐like growth factor 1 (IGF‐1) on the evolution of muscle mass, muscle strength, or physical performance are unclear. Moreover, there are no data about the relationship between these hormones and incident sarcopenia defined as low muscle mass and function. The aim of this study was to determine whether the baseline levels of sex hormones, vitamin D metabolites, and IGF‐1 predict changes in muscle mass, muscle strength, physical performance, and incident sarcopenia.

Urinary excretion of pyridinium crosslinks in healthy 4–10 year olds

Urinary pyridinoline and deoxypyridinoline, pyridinium crosslinks released during breakdown of mature collagen, might serve as useful markers of bone resorption. Before their role can be identified, reference values must be established. In this study, free pyridinoline (f-Pyr), free deoxypyridinoline (f-DPyr), and creatinine (Cr) were measured in first morning void urine samples from 250 girls and 265 boys between the ages of 4 and 10 years. Overall, there was a decrease in f-Pyr:Cr and f-DPyr:Cr ratios with increasing age in both sexes, but there was a wide range of values for individuals of similar ages. Further studies are required to assess whether urinary pyridinium crosslink excretion is sufficiently deranged in conditions affecting bone metabolism for the measurement of these compounds to be of clinical value.