Bone Mineral Content Z-scores Research Articles

Per- and polyfluoroalkyl substances and bone mineral content in early adolescence: Modification by diet and physical activity

BackgroundPer- and polyfluoroalkyl substance (PFAS) exposures may negatively impact bone mineral accrual, but little is known about potential mitigators of this relation. We assessed whether associations of PFAS and their mixture with bone mineral content (BMC) in adolescence were modified by diet and physical activity. MethodsWe included 197 adolescents enrolled in a prospective pregnancy and birth cohort in Cincinnati, Ohio (2003–2006). At age 12 years, we collected serum for PFAS measurements and used dual-energy x-ray absorptiometry to measure BMC. We calculated dietary calcium intake and Health Eating Index (HEI) scores from repeated 24-h dietary recalls, physical activity scores using the Physical Activity Questionnaire for Older Children (PAQ-C), and average moderate to vigorous physical activity (MVPA) based on accelerometry. We estimated covariate-adjusted differences in BMC z-scores per interquartile range (IQR) increase of individual PFAS concentrations using linear regression and per simultaneous IQR increase in all four PFAS using g-computation. We evaluated effect measure modification (EMM) using interaction terms between each modifier and PFAS. ResultsHigher serum perfluorooctanoic acid, perfluorooctanesulfonic acid, and perfluorononanoic acid concentrations and the PFAS mixture were associated with lower BMC z-scores. An IQR increase in all PFAS was associated with a 0.27 (−0.54, 0.01) lower distal radius BMC z-score. Associations with lower BMC were generally stronger among adolescents classified as < median for calcium intake, HEI scores, or MVPA compared to those ≥ median. The difference in distal radius BMC z-score per IQR increase in all PFAS was −0.38 (−0.72, −0.04) for those with <median calcium intake versus −0.03 (−0.48, 0.35) for ≥ median (EMM p-value = 0.16); the corresponding differences by MVPA were −0.42 (−0.76, −0.07) for < median and −0.05 (−0.42, 0.32) for ≥ median (EMM p-value = 0.13). ConclusionHealthy, calcium-rich diets and higher intensity physical activity may mitigate the adverse impact of PFAS on adolescent bone health.

Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense Child Cohort

IntroductionExposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. ObjectivesTo determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years. MethodsIn the Odense Child Cohort, Denmark, pregnant women were recruited in 2010–2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid(PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 881) and/or at age 18 months (n = 668) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. ResultsHigher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of 18-month exposure to PFNA or PFOS, BMD Z-scores were lowered by −0.10 (95 % CI −0.19;-0.00) and −0.08 (-0.17;-0.00), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. DiscussionBone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Associations of maternal gestational urinary environmental phenols concentrations with bone mineral density among 12-year-old children in the HOME Study.

Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health. We used data from 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, OH; 2003-2006). We quantified benzophenone-3, bisphenol A (BPA), 2,5-dichlorophenol, and triclosan in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry at age 12 years and calculated Z-scores for whole body (less head), total hip, femoral neck, and 1/3rd distal radius bone mineral content (BMC) and areal bone mineral density (aBMD) as well as ultra-distal radius aBMD and spine BMC and bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per doubling of maternal urinary environmental phenol concentrations in linear regression models. We also examined effect measure modification by child's sex and estimated associations of the environmental phenol mixture with BMC and aBMD using quantile g-computation. We observed generally null associations for all analytes and bone measures. Yet, in adjusted models, higher urinary 2,5-dichlorophenol concentrations were associated with higher 1/3rd distal radius BMC (β: 0.09; 95% CI: 0.02, 0.17) and aBMD (β: 0.09; 95% CI: 0.02, 0.17) Z-scores in the overall sample. In sex-stratified analyses, the magnitude of the BMC association was positive for females (β: 0.16; 95% CI: 0.06, 0.26) and null for males (β: 0.02; 95% CI: 0.08, 0.13). The environmental phenol mixture was associated with greater 1/3rd distal radius BMC and aBMD Z-scores in both sexes, which was mostly driven by benzophenone-3 in males and 2,5-dichlorophenol in females. In this prospective cohort study, we observed generally null associations for environmental phenols with BMC and aBMD at age 12 years. While there was a positive association of 2,5-dichlorophenol concentrations during fetal development with distal radius BMC and aBMD at age 12 years, future studies utilizing methods capable of differentiating cortical and trabecular bone are needed to elucidate potential mechanisms and implications for bone strength and microarchitecture.

Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense child cohort.

Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7years. In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010-2012, and their children were invited for subsequent health examinations. At 12weeks of gestation the pregnant women delivered a serum sample, and at age 18months serum was obtained from the child to measure perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n=924) and/or at age 18months (n=511) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7years, all estimates were negative although not all significant. For each doubling of prenatal or 18-month exposure to PFDA, BMD Z-scores were lowered by -0.07 (95% CI -0.10; -0.03) and -0.14 (-0.25; -0.03), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Early life organophosphate ester exposures and bone health at age 12 years: The Health Outcomes and Measures of the Environment (HOME) Study

BackgroundNo human studies have evaluated early life organophosphate ester (OPE) exposures with bone health outcomes, despite evidence of osteotoxicity. ObjectivesWe assessed associations of urinary OPE metabolites measured across early life with areal bone mineral density (aBMD) and bone mineral content (BMC) at age 12 years. MethodsAmong 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, we quantified concentrations of bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in urine collected from mothers during pregnancy and children at ages 1, 2, 3, 5, and 8 years. At age 12 years, we performed dual energy x-ray absorptiometry and calculated aBMD and BMC z-scores at six skeletal sites. We estimated overall and sex-stratified BMD/BMC z-score differences per interquartile range (IQR) increase in OPE concentrations at multiple exposure timepoints: gestation (average) and 1–3 (average), 5, and 8 years. ResultsIn adjusted models, overall associations of BCEP and BDCIPP with total hip and 1/3rd distal radius aBMD and BMC varied significantly by exposure timepoint, as did BDCIPP with whole body aBMD. For example, differences (95 % CI) in total hip aBMD z-score per IQR increase in BDCIPP were 0.33 (0.01, 0.64), −0.10 (−0.34, 0.14), −0.18 (−0.40, 0.05), and 0.14 (−0.09, 0.38) for concentrations during gestation and at 1–3, 5, and 8 years, respectively. Overall DnBP and DPHP associations were generally null at all timepoints. We observed sex-specific associations for some timepoints and skeletal sites. For example, an IQR increase in 8-year DPHP was associated with a 0.21 (0.05, 0.38) greater total hip aBMD z-score among females but −0.19 (−0.43, 0.05) lower z-score among males. DiscussionEarly life OPE exposures may be associated with sex- and exposure period-dependent alterations in early adolescent bone mineral accrual and strength.

Associations of pregnancy phthalate concentrations and their mixture with early adolescent bone mineral content and density: The Health Outcomes and Measures of the Environment (HOME) study.

The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce. To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort. We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation. In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: -0.13, 1.10) greater ultradistal radius BMD Z-score in females. In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.

Associations of Maternal Serum Perfluoroalkyl Substances Concentrations with Early Adolescent Bone Mineral Content and Density: The Health Outcomes and Measures of the Environment (HOME) Study.

Background:Per- and polyfluoroalkyl substances (PFAS) may impair bone accrual and strength via endocrine disruption and nuclear receptor agonism, but human studies are primarily of adults or cross-sectional.Objectives:We assessed associations of individual PFAS and their mixture during pregnancy with child bone mineral content (BMC) and areal bone mineral density (aBMD) at age 12 y.Methods:Among 206 mother–child pairs enrolled in a prospective cohort (2003–2006), we quantified perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in maternal serum collected during gestation or delivery. When children were age 12 y, we performed dual energy X-ray absorptiometry and calculated BMC, aBMD, and bone mineral apparent density (BMAD) -scores for six skeletal sites. We estimated covariate-adjusted -score differences per doubling of individual PFAS using linear regression and assessed the PFAS mixture using quantile g-computation and Bayesian kernel machine regression. We explored whether associations were modified by child’s sex or mediated by whole-body lean mass.Results:In covariate-adjusted models, we found that higher maternal serum concentrations of PFOA, PFNA, and the PFAS mixture were associated with lower total hip and forearm (one-third distal radius) BMC -scores in children. Differences in forearm BMC -scores were [95% confidence interval (CI): , 0.01] and (95% CI: , ) per doubling of PFOA and PFNA, respectively, and (95% CI: , ) per quartile increase in the PFAS mixture. Child’s sex modified PFOA associations for some skeletal sites; for example, differences in spine BMAD -score per doubling were (95% CI: , ) among males and 0.07 (95% CI: , 0.30) among females (modification ). Except for PFNA among females, these associations were not mediated by whole-body lean mass.Discussion:Maternal PFAS concentrations during pregnancy may be associated with lower bone mineral accrual and strength in early adolescence. https://doi.org/10.1289/EHP9424

Intermachine differences in DXA measurements vary by skeletal site, and impact the assessment of low bone density in children.

Bone mineral content (BMC) and areal-bone mineral density (aBMD) measurements of the lumbar spine (LS) and whole body less head (WBLH) by dual energy X-ray absorptiometry (DXA) are recommended for bone health assessment in children. Intermachine differences were not considered previously in formulating these recommendations. DXA measurements of the LS, WBLH, total hip, femoral neck and distal 1/3 radius from the Bone Mineral Density in Childhood Study were examined. Healthy children, ages 6 to 16years, from five clinical centers participated. The same spine, whole body, and femur phantoms were measured on each Center's DXA machine. Percentage of individuals with low BMC or aBMD (Z-score<-1.5) was determined. Clinical center differences were evaluated by analysis of covariance adjusting for height and BMI Z-score, calcium intake, physical activity, Tanner stage and bone age. Logistic regression assessed odds of low BMC or aBMD across clinical centers. Significant differences among Clinical Centers (p<0.05) were evident in adjusted mean BMC and aBMD Z-scores (n=1503) for all skeletal sites. WBLH BMC and aBMD Z-scores had the greatest range across centers (-0.13 to 0.24, and -0.17 to 0.56, respectively). The percentage of children with Z-scores less than -1.5 varied among Clinical Centers from 1.9 [95%CI 0.8, 4.5] to 8.1 [95%CI 5.7, 11.3] for WBLH BMC, 1.1 [95%CI 0.4, 3.5] to 6.3 [95%CI 3.8, 10.1] for WBLH aBMD, and from 4.4 [95%CI 2.8, 7.0] to 12.6 [95%CI 9.3, 16.9] for distal 1/3 radius aBMD. For each skeletal site except total hip aBMD and femoral neck BMC, at least one center had significantly lower odds of low bone density. By design, our reference ranges capture intermachine variability. Most clinical centers don't know where their machine falls within the range of intermachine variability, and this may affect diagnosis of children evaluated for conditions that threaten bone health. Total hip scans showed the least, and whole body scans showed the most intermachine variability. Pediatric bone health assessment recommendations should recognize intermachine differences and address this important issue.

Bone Health in Relation to Vitamin-D Status and Serum Adipokines in Obese Egyptian Children

Childhood obesity has been linked to an increase in fracture risk, so the impact of obesity on bone metabolism is becoming a focus of attention to identify factors that may affect bone health in obese children. Therefore, this study aimed to examine the association between serum 25-Hydroxy vitamin D [25(OH) D], adipokines and bone status in obese children. This case control study was executed in the Child Health Clinic in Medical and Scientific Centre of Excellence, National Research Centre (NRC), 100 obese and 80 non-obese age- and sex-matched children were enrolled in our study with mean age of (10.12±2.34 &amp; 9.62±1.67 years) respectively. Anthropometric measurements, femoral neck bone mineral density (BMD) and its Z-score, bone mineral content (BMC) were measured using dual-energy X-ray absorptiometry (DXA) in relation to body weight (kg), we also determined serum 25(OH) D, adiponectin, leptin and lipid profile. HOMA-IR was calculated to assess insulin resistance. It was found that BMC and BMD Z-score adjusted for weight were significantly lower in obese children as compared to controls (all p&lt;0.05). Obese children had lower levels of 25(OH) D and adiponectin (P&lt;0.01), while higher levels of leptin, total cholesterol (TC) and triglycerides (TG) compared to controls (P&lt;0.01). Both BMC and BMD Z-score showed positive association with 25(OH) D and adiponectin (P&lt;0.01) and negative association with HOMA-IR, TG and TC (P&lt;0.05). Linear regression analysis showed that 25(OH) D was the most effective factor predicting BMD Z-score and BMC in obese children. It is concluded that, obesity is negatively related to bone health in childhood. Those obese children are at increased risk for vitamin D insufficiency, which shows an obvious relationship to lower bone mass, raising the question of supplementation to prevent the deleterious effect of its deficiency on bones and reducing future risk of fracture and osteoporosis.

Early childhood as a sensitive period for the effect of growth on childhood bone mass: Evidence from Generation XXI birth cohort.

To identify sensitive periods for the effect of early life growth on childhood bone mass we compared the associations between weight and length/height velocities from birth to age six and bone mineral content (BMC) and areal density (aBMD) at 7 years of age. We analyzed data from 1853 participants from the Generation XXI birth cohort scanned with a whole body dual-energy X-ray absorptiometry system. Velocities of growth in weight and length/height were obtained through linear spline multilevel models on the basis of data collected during routine health examinations. Using linear regression we computed associations of birth weight, birth length, five weight velocities ("early neonatal": 0-10 days, "early infancy": 10 days-3 months, "late infancy": 3-12 months, "early childhood": 1-3 years, and "later childhood": 3-6 years) and four length/height velocities ("early infancy": 0-3 months, "late infancy": 3-12 months, "early childhood": 1-3 years, and "later childhood": 3-6 years) with outcomes BMC, aBMD, height and height-adjusted BMC at age seven. Confounding by maternal and child characteristics was addressed and effects of growth velocities were adjusted to preceding growth. Weight and length/height velocities up to the age of six were associated with increased bone mass, areal density and height at 7 years with the strongest associations observed for growth in early childhood. In this age period, after concurrent height and confounder adjustment, one standard deviation (SD) increase in weight velocity was associated with higher BMC z-scores: 0.27 (95%CI: 0.22, 0.32) in girls and 0.24 (95%CI: 0.19, 0.29) in boys. Height velocity was also associated with greater height-adjusted BMC z-score: 0.12 (95%CI: 0.07, 0.17) per SD in girls and 0.11 (95%CI: 0.06, 0.16) in boys. The pattern of associations was similar, albeit attenuated, after adjusting for preceding growth. Growth in second and third years of life may represent a sensitive period for the effect of growth on childhood bone mass, partly through their effect on concurrent body size.

Bone Health, Body Composition, and Vitamin D Status of Black Preadolescent Children in South Africa.

Optimal bone health is important in children to reduce the risk of osteoporosis later in life. Both body composition and vitamin D play an important role in bone health. This study aimed to describe bone health, body composition, and vitamin D status, and the relationship between these among a group of conveniently sampled black preadolescent South African children (n = 84) using a cross-sectional study. Body composition, bone mineral density (BMD), and bone mineral content (BMC) were assessed using dual x-ray absorptiometry. Levels of 25-hydroxyvitamin D (25(OH)D) (n = 59) were assessed using dried blood spots. A quarter (25%) of children presented with low bone mass density for their chronological age (BMD Z-score < −2) and 7% with low BMC-for-age (BMC Z-score < −2), while only 34% of the children had sufficient vitamin D status (25(OH)D ≥ 30 ng/mL). Lean mass was the greatest body compositional determinant for variances observed in bone health measures. Body composition and bone health parameters were not significantly different across vitamin D status groups (p > 0.05), except for lumbar spine bone mineral apparent density (LS-BMAD) (p < 0.01). No association was found between bone parameters at all sites and levels of 25(OH)D (p > 0.05). Further research, using larger representative samples of South African children including all race groups is needed before any conclusions and subsequent recommendation among this population group can be made.

Postmenopausal osteoporotic fracture-associated COLIA1 variant impacts bone accretion in girls.

Over the past two decades, a low frequency variant (rs1800012) within the first intron of the type I collagen alpha 1 (COLIA1) gene has been implicated in lower areal BMD (aBMD) and increased risk of osteoporotic fracture. This association is particularly strong in postmenopausal women, in whom net bone loss arises in the context of high bone turnover. High bone turnover also accompanies childhood linear growth; however, the role of rs1800012 in this stage of net bone accretion is less well understood. Thus, we assessed the association between rs1800012 and aBMD and bone mineral content (BMC) Z-scores for the 1/3 distal radius, lumbar spine, total hip, and femoral neck total body less head in the Bone Mineral Density in Childhood Study, a mixed-longitudinal cohort of children and adolescents (total n = 804 girls and 771 boys; n = 19 girls and 22 boys with the TT genotype). Mixed effects modeling, stratified by sex, was used to test for associations between rs1800012 and aBMD or BMC Z-scores and for pubertal stage interactions. Separately, SITAR growth modeling of aBMD and BMC in subjects with longitudinal data reduced the complex longitudinal bone accrual curves into three parameters representing a-size, b-timing, and c-velocity. We tested for differences in these three parameters by rs1800012 genotype using t-tests. Girls with the TT genotype had significantly lower aBMD and BMC Z-scores prior to puberty completion (e.g. spine aBMD-Z P-interaction = 1.0 × 10-6), but this association was attenuated post-puberty. SITAR models revealed that TT girls began pubertal bone accrual later (b-timing; e.g. total hip BMC, P = 0.03). BMC and aBMD Z-scores also increased across puberty in TT homozygous boys. Our data, along with previous findings in post-menopausal women, suggest that rs1800012 principally affects female bone density during periods of high turnover. Insights into the genetics of bone gain and loss may be masked during the relatively quiescent state in mid-adulthood, and discovery efforts should focus on early and late life.

Revised reference curves of bone mineral density according to age and sex for Iranian children and adolescents.

Bone health evaluation requires an appropriate reference database that can identify the bone deficit according to age, sex, puberty, and race. The aim of this study was to determine bone mineral density Z-scores in Iranian children and adolescents and their comparability with other reference data. A sample of 476 healthy children and adolescents, aged 9-18years, from Kawar (an urban community, 50km east of Shiraz, Iran) was selected and bone mineral measurements of the lumbar spine, femoral neck, and total body (less head) were done. Sex-specific height-for-age, weight-for-age, and BMI-for-age Z-scores, as well as bone mineral density Z-scores, were calculated. Extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) of the total body less head, lumbar spine, and femoral neck, for ages 9-18years were constructed relative to sex and age. We found that median, - 2SD, and + 2SD curves for the lumbar spine aBMD were higher in Iranian subjects than in the American participants, but the curves of the femoral neck and total body were lower. Also, we showed that subjects with a lower height-for-age Z-score had a lower BMC and aBMD Z-score in the lumbar spine, femoral neck, and total body (p < 0.001). Relevant differences in bone mineral density and its curves exist between Iranian children and adolescents and other databases, revealing a significant potential for misdiagnosis. However, our results can be used to provide reference databases to assist clinicians in interpreting, assessing, and monitoring bone densitometry.

Decreased bone turnover in HIV-infected children on antiretroviral therapy

SummaryIn this study, we evaluated the relationships between immune activation, bone turnover, and bone mass in virally suppressed HIV-infected children and HIV-uninfected children in South Africa. We found that decreased bone mass may occur or persist independent of immune activation and altered bone turnover.PurposeHIV-infected children and adolescents have deficits in skeletal growth which include decreases in bone mass and alterations in bone microarchitecture. However, the mechanism by which HIV infection compromises bone accrual in children and adolescents is unclear. The goal of this study was to evaluate the relationships between immune activation, bone turnover, and bone mass in a group of pre-pubertal HIV-infected children randomized to remain on ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy (ART) or switch to efavirenz-based ART in South Africa virally suppressed at the time of this study.MethodsThis cross-sectional analysis included 219 HIV-infected and 180 HIV-uninfected children enrolled in the CHANGES Bone Study conducted in Johannesburg, South Africa. Whole body (WB) bone mineral content (BMC) was assessed by dual x-ray absorptiometry and WB BMC Z-scores adjusted for sex, age, and height were generated. Bone turnover markers, including C-telopeptide of type 1 collagen (CTx) and procollagen type I N-terminal propeptide (P1NP), were analyzed. Markers of immune activation were also measured, including cytokines IL-6 and TNF-alpha, as well as soluble CD14 and high-sensitivity C-reactive protein (CRP).ResultsCompared to uninfected controls, HIV-infected children had lower WB BMC Z-scores, similar IL-6 and TNF-alpha, higher soluble CD14 and high-sensitivity CRP, and lower markers of bone resorption (CTX) and bone formation (P1NP). Bone turnover markers were not different in those remaining on LPV/r or switched to efavirenz.ConclusionsOur findings suggest that in HIV-infected children with viral suppression, decreased bone accrual may occur or persist independent of immune activation and altered bone turnover.

Assessment of Sex Differences in Body Composition Among Adolescents With Anorexia Nervosa

PurposeTo compare deficits in fat mass (FM) and lean body mass (LM) among male and female adolescents with anorexia nervosa (AN) and to identify other covariates associated with body composition. MethodsWe retrospectively reviewed electronic medical records of all subjects aged 9–20 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of AN and dual-energy x-ray absorptiometry scans after initial evaluation at Stanford between March 1997 and February 2011. From the dual-energy x-ray absorptiometry scans, LM and FM results were converted to age-, height-, sex-, and race-specific Z-scores for age using the National Health and Nutrition Examination Survey reference data. ResultsA total of 16 boys and 119 girls with AN met eligibility criteria. The FM Z-score in girls with AN (−3.24 ± 1.50) was significantly lower than that in boys with AN (−2.41 ± .96) in unadjusted models (p = .007). LM was reduced in both girls and boys with AN, but there was no significant sex difference in LM Z-scores. In multivariate models, lower percentage median body mass index was significantly associated with lower FM Z-scores (β = .08, p < .0001) and lower LM Z-score (β = .03, p = .0002), whereas lower whole body bone mineral content Z-score was significantly associated with lower LM Z-score (β = .21, p = .0006). ConclusionsFM deficits in girls were significantly greater than those in boys with AN in unadjusted models; however, the degree of malnutrition appeared to be the primary factor accounting for this difference. There were no significant sex differences in FM or LM in adjusted models.

Assessment of sex differences in bone deficits among adolescents with anorexia nervosa.

The objective of this study was to compare sex differences in bone deficits among adolescents with anorexia nervosa (AN) and to identify other correlates of bone health. Electronic medical records of all patients 9-20 years of age with a DSM-5 diagnosis of AN who were evaluated by the eating disorders program at Stanford with dual-energy X-ray absorptiometry (DXA) between March 1997 and February 2011 were retrospectively reviewed. Whole body bone mineral content Z-scores and bone mineral density (BMD) Z-scores at multiple sites were recorded using the Bone Mineral Density in Childhood Study (BMDCS) reference data. A total of 25 males and 253 females with AN were included, with median age 15 years (interquartile range [IQR] 14-17) and median duration of illness 9 months (IQR 5-13). Using linear regression analyses, no significant sex differences in bone deficits were found at the lumbar spine, total hip, femoral neck, or whole body when controlling for age, %mBMI, and duration of illness. Lower %mBMI was significantly associated with bone deficits at all sites in adjusted models. This is the first study to evaluate sex differences in bone health among adolescents with AN, using novel DSM-5 criteria for AN and robust BMDCS reference data. We find no significant sex differences in bone deficits among adolescents with AN except for a higher proportion of females with femoral neck BMD Z-scores <-1. Degree of malnutrition was correlated with bone deficits at all sites. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:352-358).

Bone health measures in glucocorticoid-treated ambulatory boys with Duchenne muscular dystrophy

Osteoporosis is a major problem in boys with Duchenne Muscular Dystrophy (DMD), attributable to muscle weakness and glucocorticoid therapy. Consensus regarding bone health assessment and management is lacking. Lumbar spine areal bone mineral density (defined as bone mass per area of bone) by dual-energy X-ray absorptiometry (DXA) is frequently the primary measure used, but has limitations for boys with DMD. We retrospectively studied 292 ambulant glucocorticoid-treated boys with DMD categorized by functional mobility score, FMS 1, 2 or 3. We assessed DXA whole body and lumbar spine areal bone mineral density and content Z-scores adjusted for age and height, lateral distal femur areal bone mineral density Z-scores, frequency of fractures, and osteoporosis by International Society for Clinical Densitometry 2013 criteria. Whole body and femoral DXA indices decreased, while spine fractures increased, with declining motor function. Lumbar spine areal bone mineral density Z-scores appeared to improve with declining motor function. Bone mineral content Z-scores were consistently lower than corresponding bone mineral density Z-scores. Our findings highlight the complexity of assessing bone health in boys with DMD. Bone health indices worsened with declining motor function in ambulant boys, but interpretation was affected by measure and skeletal site examined. Whole body bone mineral content may be a valuable measure in boys with DMD. Lumbar spine areal bone mineral density Z-score as an isolated measure could be misleading. Comprehensive management of osteoporosis in boys with DMD should include vertebral fracture assessment.

Anthropometric adjustments are helpful in the interpretation of BMD and BMC Z-scores of pediatric patients with Prader-Willi syndrome.

Bone mineral density (BMD) is decreased in patients with Prader-Willi syndrome (PWS). Because of largely abnormal body height and weight, traditional BMD Z-scores may not provide accurate information in this patient group. The goal of the study was to assess a cohort of individuals with PWS and characterize the development of low bone density based on two adjustment models applied to a dataset of BMD and bone mineral content (BMC) from dual-energy X-ray absorptiometry (DXA) measurements. Fifty-four individuals, aged 5-20years with genetically confirmed PWS, underwent DXA scans of spine and hip. Thirty-one of them also underwent total body scans. Standard Z-scores were calculated for BMD and BMC of spine and total hip based on race, sex, and age for all patients, as well as of whole body and whole-body less head for those patients with total-body scans. Additional Z-scores were generated based on anthropometric adjustments using weight, height, and percentage body fat and a second model using only weight and height in addition to race, sex, and age. As many PWS patients have abnormal anthropometrics, addition of explanatory variables weight, height, and fat resulted in different bone classifications for many patients. Thus, 25-70% of overweight patients, previously diagnosed as normal, were subsequently diagnosed as below normal, and 40-60% of patients with below-normal body height changed from below normal to normal depending on bone parameter. This is the first study to include anthropometric adjustments into the interpretation of BMD and BMC in children and adolescents with PWS. This enables physicians to get a more accurate diagnosis of normal versus abnormal BMD and BMC and allows for early and effective intervention.

Rare EN1 Variants and Pediatric Bone Mass.

A recent whole-genome sequencing study in search of variation associated with adult areal bone mineral density (aBMD) identified rare variants near EN1, with markedly large effect sizes, and a common variant near SOX6. To understand the developmental effects of these loci, we sought to determine if they were associated with pediatric dual-energy X-ray absorptiometry-derived aBMD and bone mineral content (BMC) and if the associations were modified by sex. Our sample comprised 733 females and 685 males of European ancestry enrolled in the longitudinal Bone Mineral Density in Childhood Study (up to 7 annual study visits). Sex- and age-specific Z-scores, adjusted for height, were calculated for the total hip, femoral neck, spine, and distal radius. Total body less head (TBLH) BMC Z-scores were also calculated. The previously reported single nucleotide polymorphisms (SNPs) near EN1 and SOX6 were derived from our imputed data set. Linear mixed-effects models were used to test associations between each SNP and bone Z-scores, plus interactions with sex were explored. The rare T allele of lead EN1 SNP rs11692564 was associated with higher aBMD Z-score for total hip (beta = 0.62, p = 9.0 × 10(-4) ) and femoral neck (beta = 0.53, p = 0.010). In sex-stratified analyses, this variant was associated with higher bone Z-scores in females only, with the associations being strongest for total hip (sex interaction p = 1.9 × 10(-4) ; beta females = 0.86, p = 6.6 × 10(-6) ) and femoral neck (sex interaction p = 0.016; beta females = 0.73, p = 0.001). The common G allele of SOX6 SNP rs11024028 was associated with higher aBMD Z-score for total hip (beta = 0.12, p = 0.009), femoral neck (beta = 0.13, p = 0.003), and TBLH-BMC (beta = 0.09, p = 0.007); furthermore, this association strengthened in males in the sex-stratified analyses. Our findings reveal that rare genetic variation near EN1 and common variation near SOX6 operates in childhood and has implications for the lifelong risk of osteoporosis and fracture. The sex differences observed need to be independently replicated. © 2016 American Society for Bone and Mineral Research.

WHOLE BODY AND REGIONAL BONE MINERAL CONTENT AND DENSITY IN WOMEN AGED 20-75 YEARS.

Dual-energy X-ray absorptiometry (DXA) allows measurement of whole body (WB) and regional bone mineral content (BMC) and density (BMD). To measure WB and regional bone area, BMC and BMD (arms, legs, ribs and pelvis) in women of different ages. 140 women participated (age range 20-75 yrs). Three subgroups were built: 20-44 yr (30 premenopausal women), 45-59 (80 women), and 60-75 (30 women). WB DXA was performed on a Hologic QDR 4500 A bone densitometer (Hologic Inc., Bedford MA). WB BMD T-scores were calculated by using the manufacturer-provided and the NHANES 1999-2004 reference databases, while the WB BMC Z-scores - based on the latter. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). WB BMC and BMD Z-scores were consistently lower than the reference databases showing a difference of about 0.4 - 0.5 SD. The arms, legs and ribs lost more BMC after the age of 50-55, while the pelvis - much earlier. The total decreases in BMC were highest in the pelvis (26.36 %), followed by the arms (16.81 %) and whole body (15.91 %), while the bone area decreased mostly in the pelvis (13.23 %). The age-related declines in regional BMC, bone areas and BMD follow different patterns in appendicular and axial bones.