Bone Mineral Density In Childhood Study Research Articles

Bone Accrual Trajectories in Children and Adolescents with Perinatal HIV Infection.

Low bone mineral density (BMD) has been reported in children and adolescents living with perinatally-acquired HIV (PHIV). Little is known about their bone accrual through puberty compared to an uninfected healthy cohort. To compare bone accrual in PHIV and healthy children. PHIV children aged 7-16 years had dual energy X-ray absorptiometry (DXA) at entry, 2 years, and then at least 2 years later. Bone accrual was compared to healthy children from the Bone Mineral Density in Childhood Study (BMDCS). United States academic clinical research centers. 172 PHIV; 1321 BMDCS. We calculated height-adjusted whole-body and spine BMD and bone mineral content (BMC) Z-scores in PHIV using BMDCS reference curves. We fit piecewise weighted linear mixed effects models with change points at 11 and 15 years, adjusted for age, sex, race, height Z-score, and Tanner stage, to compare BMD and BMC Z-scores across actual age by cohort.Main Outcome Measure: BMD/BMC Z-scores. Height-adjusted whole-body BMD and BMC Z-scores in PHIV were lower across age compared to BMDCS children. Spine BMD Z-score across age was higher in PHIV after height adjustment. Whole-body and spine bone area tended to be lower in PHIV. PHIV had slower accrual in whole-body and spine bone area before 14 years. After 15 years, bone area accruals were similar, as were height-adjusted spine BMC Z-scores, across age. PHIV had persistent deficits in all measures except height-adjusted spine BMD and BMC Z-scores. Data are needed on PHIV followed to adulthood.

Trajectory of body mass index and obesity in children with Crohn's disease compared to healthy children.

There is increasing recognition that children with Crohn's Disease (CD) can develop obesity. Using the RISK Study, an inception cohort of pediatric CD participants, and Bone Mineral Density in Childhood Study (BMDCS), a longitudinal cohort of healthy children, multivariable linear mixed effects, generalized linear mixed effects, and logistic regression models were used to evaluate factors associated with change in body mass index z-score (BMIZ), obesity, and excessive weight gain, respectively. 1029 CD participants (625 exposed to antitumor necrosis factor (anti-TNF) therapy) and 1880 healthy children were included. Change in BMIZ was higher in CD exposed to anti-TNF as compared to CD unexposed to anti-TNF and the healthy reference group. Sex, age, baseline BMIZ, C-reactive protein, anti-TNF, and steroids were associated with changes in BMIZ in CD. CD exposed (odds ratio [OR] 4.81, confidence interval [CI] 4.00-5.78) and unexposed (OR 3.14, CI 2.62-3.76) had a greater likelihood of becoming obese versus the healthy reference group. While the prevalence of obesity was higher at baseline in the healthy reference group (21.3%) versus CD participants (8.5% exposed vs. 11.1% unexposed), rates of obesity were similar by the end of follow-up (21.4% healthy vs. 20.3% exposed vs. 22.5% unexposed). Anti-TNF therapy was an independent risk factor for the development of obesity and excessive weight gain in CD participants. Patients with CD have dynamic changes in BMIZ over time, and while for most, this is restorative, for some, this can lead to obesity and excessive weight gain. It is important to understand the factors that may lead to these changes, including anti-TNF therapy. Counseling of patients and early lifestyle intervention may be necessary.

Reference ranges for body composition indices by dual energy X-ray absorptiometry from the Bone Mineral Density in Childhood Study Cohort

BackgroundBody composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile. ObjectivesThis study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS). MethodsThis is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5–19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score. ResultsWe obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and–2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian −0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black −0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score. ConclusionsThese reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.

Trabecular Bone Score (TBS) Varies with Correction for Tissue Thickness Versus Body Mass Index: Implications When Using Pediatric Reference Norms.

Trabecular bone score (TBS) derived from secondary analysis of lumbar spine dual-energy X-ray absorptiometry (DXA) scans improves fracture prediction independent of bone mineral density (BMD) in adults. The utility of TBS to assess fracture risk in younger patients has not been established because pediatric norms have been lacking. Robust TBS reference data from the Bone Mineral Density in Childhood Study (BMDCS) have been published. TBS values for the BMDCS study were derived using an algorithm that accounts for tissue thickness (TBSTH ) rather than the commercially available algorithm that adjusts for body mass index (BMI; TBSBMI ). We examined the magnitude of differences in TBSTH and TBSBMI in a cohort of 189 healthy youth. TBS values using both algorithms increased with age and pubertal development in a similar pattern. However, TBSBMI values were systematically and significantly higher than TBSTH (mean=0.06, p< 0.0001). The difference between calculated TBSBMI and TBSTH was not uniform. Differences were greater at lower TBS values, in males, in older individuals, in those at later Tanner stages, and in those with a greater BMI Z-score. These systematic differences preclude the development of a simple formula to allow conversion of TBSBMI to TBSTH "equivalents." Because of these systematic differences in these two algorithms, using an individual's TBSBMI to calculate a Z-score using the BMDCS TBSTH reference values results in a falsely higher TBS Z-score (differences mean=0.73, interquartile range [IQR]=0.3 to 1.6). Until TBSTH software for Hologic DXA equipment becomes commercially available, BMDCS TBS reference norms should not be used. © 2023 American Society for Bone and Mineral Research (ASBMR).

Trabecular Bone Score Reference Values for Children and Adolescents According to Age, Sex, and Ancestry.

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n= 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r= 0.47) than for aBMD or BMAD Z-scores (r= 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).

Genetically Determined Later Puberty Impacts Lowered Bone Mineral Density in Childhood and Adulthood.

Later puberty associates with lower areal bone mineral density (aBMD), and both are risk factors for osteoporosis. However, the association between puberty timing-associated genetic variants and aBMD during development, and the causal relationship between puberty timing and aBMD, remain uncharacterized. We constructed sex-specific polygenic risk scores (GRS) consisting of 333 genetic variants associated with later puberty in European-descent children in the Bone Mineral Density in Childhood Study (BMDCS), consisting of a longitudinal cohort with up to seven assessments (n = 933) and a cross-sectional cohort (n = 486). These GRS were tested for associations with age- and sex-specific aBMD Z-scores at the lumbar spine (LS), femoral neck (FN), total hip, and distal radius, accounting for clinical covariates using sex-stratified linear mixed models. The causal relationship between puberty timing and aBMD was tested in the BMDCS and in publicly available adult data (GEFOS consortium) using two-sample Mendelian randomization (MR). The puberty-delaying GRS was associated with later puberty and lower LS-aBMD in the BMDCS in both sexes (combined beta ± SE = -0.078 ± 0.024; p = 0.0010). In the MR framework, the puberty-delaying genetic instrument also supported a causal association with lower LS-aBMD and FN-aBMD in adults of both sexes. Our results suggest that pubertal timing is causal for diminished aBMD in a skeletal site- and sex-specific manner that tracks throughout life, potentially impacting later risk for osteoporosis, which should be tested in future studies. © 2017 American Society for Bone and Mineral Research.

Impact of low-weight severity and menstrual status on bone in adolescent girls with anorexia nervosa.

Clinicians currently use different low-weight cut-offs both to diagnose anorexia nervosa (AN) and to determine AN severity in adolescent girls. The purpose of this study was to evaluate the clinical utility of existing cut-offs and severity criteria by determining which are most strongly associated with risk for low bone mineral density (BMD). Height adjusted BMD Z scores were calculated for 352 females: 262 with AN and 90 healthy controls (controls) (12-20.5 years), using data from the BMD in Childhood Study, for the lumbar spine, whole body less head, and total hip. For most cut-offs used to define low weight (5th or 10th BMI percentile, BMI of 17.5 or 18.5, and 85 or 90% of median BMI), AN had lower BMD Z scores than controls. AN at >85 or >90% expected body weight for height (EBW-Ht) did not differ in BMD Z scores from controls, but differed significantly from AN at ≤85 or ≤90% EBW-Ht. Among AN, any amenorrhea was associated with lower BMD. AN had lower BMD than controls across DSM-5 and The Society for Adolescent Health and Medicine (SAHM) severity categories. The SAHM moderate severity classification was differentiated from the mildly malnourished classification by lower BMD at hip and spine sites. Amenorrhea and %EBW-Ht ≤ 85 or ≤ 90% are markers of severity of bone loss within AN. Among severity categories, BMI Z scores (SAHM) may have the greatest utility in assessing the degree of malnutrition in adolescent girls that corresponds to lower BMD.

Body Composition and BMI Growth Charts in Children With Down Syndrome.

New US Down syndrome (DS) BMI growth charts were recently published, but their utility in identifying children with excess adiposity or increased cardiometabolic risk (CMR) remains unknown. We sought to compare the ability of the Centers for Disease Control and Prevention (CDC) BMI 85th percentile and DS-specific BMI 85th percentile to identify excess adiposity in children with DS. Participants with DS aged 10 to 20 years were enrolled in a cross-sectional CMR study. Data from typically developing children enrolled in the Bone Mineral Density in Childhood Study (BMDCS) were used for comparison. Sensitivity and specificity were calculated to assess the CDC BMI 85th percentile in the BMDCS and DS groups, and the DS-specific BMI 85th percentile in the DS group, relative to fat mass index (FMI) ≥80th percentile, a threshold associated with increased CMR. Included were 121 DS participants (age 14.8 ± 3.3 years, 57% girls) and 7978 BMDCS reference data points (age 15.0 ± 3.0 years, 51.3% girls). The CDC BMI 85th percentile identified FMI ≥80th percentile with 96.9% sensitivity and 87.4% specificity in typically developing children. Similarly, the CDC BMI 85th percentile identified FMI ≥80th percentile with 100% sensitivity and 78.3% specificity in children with DS. In contrast, the sensitivity of the DS-specific BMI 85th percentile was only 62.3% (P < .0001), but was 100% specific. For children with DS ≥10 years, the CDC BMI growth chart 85th percentile is a better indicator of excess adiposity, than the new DS-specific BMI charts. Additional studies are needed to clarify the relationships of BMI and FMI with CMR in DS.

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).

Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children.

In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature. The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children. Data from the Bone Mineral Density in Childhood Study (BMDCS) were used to develop adjustment methods that were validated using an independent cross-sectional sample of healthy children from the Reference Data Project (RDP). We conducted the study in five clinical centers in the United States. We included 1546 BMDCS and 650 RDP participants (7 to 17 yr of age, 50% female). No interventions were used. We measured spine and whole body (WB) BMC and BMD Z-scores for age (BMC/BMD(age)), height age (BMC/BMD(height age)), height (BMC(height)), bone mineral apparent density (BMAD(age)), and height-for-age Z-score (HAZ) (BMC/BMD(haz)). Spine and WB BMC/BMD(age)Z and BMAD(age)Z were positively (P < 0.005; r = 0.11 to 0.64) associated with HAZ. Spine BMD(haz) and BMC(haz)Z were not associated with HAZ; WB BMC(haz)Z was modestly associated with HAZ (r = 0.14; P = 0.0003). All other adjustment methods were negatively associated with HAZ (P < 0.005; r = -0.20 to -0.34). The deviation between adjusted and BMC/BMD(age) Z-scores was associated with age for most measures (P < 0.005) except for BMC/BMD(haz). Most methods to adjust BMC/BMD Z-scores for height were biased by age and/or HAZ. Adjustments using HAZ were least biased relative to HAZ and age and can be used to evaluate the effect of short or tall stature on BMC/BMD Z-scores.