Total Body Less Head Research Articles

Cross-calibration of two dual-energy X-ray absorptiometry devices for the measurement of body composition in young children

This study aimed to cross-calibrate body composition measures from the GE Lunar Prodigy and GE Lunar iDXA in a cohort of young children. 28 children (mean age 3.4 years) were measured on the iDXA followed by the Prodigy. Prodigy scans were subsequently reanalysed using enCORE v17 enhanced analysis (“Prodigy enhanced”). Body composition parameters were compared across three evaluation methods (Prodigy, Prodigy enhanced, iDXA), and adjustment equations were developed. There were differences in the three evaluation methods for all body composition parameters. Body fat percentage (%BF) from the iDXA was approximately 1.5-fold greater than the Prodigy, whereas bone mineral density (BMD) was approximately 20% lower. Reanalysis of Prodigy scans with enhanced software attenuated these differences (%BF: − 5.2% [95% CI − 3.5, − 6.8]; and BMD: 1.0% [95% CI 0.0, 1.9]), although significant differences remained for all parameters except total body less head (TBLH) total mass and TBLH BMD, and some regional estimates. There were large differences between the Prodigy and iDXA, with these differences related both to scan resolution and software. Reanalysis of Prodigy scans with enhanced analysis resulted in body composition values much closer to those obtained on the iDXA, although differences remained. As manufacturers update models and software, researchers and clinicians need to be aware of the impact this may have on the longitudinal assessment of body composition, as results may not be comparable across devices and software versions.

Relationships Between 25-Hydroxyvitamin D, Parathyroid Hormone, and Bone Mass in 4-Year-Old Children in Dhaka, Bangladesh

ObjectivesElevated serum parathyroid hormone (PTH) concentration was incidentally observed in a high proportion of children in a study in Dhaka, Bangladesh. We explored potential correlates of elevated PTH by estimating the association of PTH with 25-hydroxyvitamin D (25(OH)D) and associations of 25(OH)D and PTH with bone outcomes.MethodsData were obtained from the BONe and mUScle health in Kids study (BONUSKids; NCT03537443). Total-body less head (TBLH) bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by dual-energy X-ray absorptiometry (DXA). Serum PTH and 25(OH)D were analyzed by chemiluminescent immunoassay and liquid chromatography-tandem mass spectrometry, respectively. BONUSKids participants (n = 642) with DXA, PTH and 25(OH)D data at 4 years were included. Associations between 25(OH)D, PTH and bone outcomes were estimated using unadjusted linear and two-phase linear spline regression models. Model fit was compared using AIC.ResultsAmong the 534 children who met inclusion criteria, 43% were vitamin D deficient (< 30nmol/L) and 30% had PTH > 6.9pmol/L. A non-linear inverse relationship was observed between 25(OH)D and PTH. Model fit was optimized with an inflection point at 25nmol/L, above which the association attenuated (< 25nmol/L: −0.16pmol/L per 1nmol/L change in 25(OH)D [95%CI −0.23, −0.10]; ≥ 25nmol/L: –0.02pmol/L [95% CI −0.04, −0.008]. 25(OH)D was positively linearly associated with TBLH BMC (0.39g per 1nmol/L change in 25(OH)D [95%CI 0.10: 0.69]) and aBMD (0.0004g/cm2 per 1nmol/L change in 25(OH)D [95% CI 0.0002, 0.0006]). There was no significant association between PTH and TBLH BMC. The non-linear association between PTH and TBLH aBMD was negative at PTH > 4pmol/L (< 4pmol/L: 0.002g/cm2 per 1pmol/L change in PTH [95% CI –0.006, 0.01], ≥ 4pmol/L: −0.002g/cm2 [95% CI −0.0038, −0.0002]).ConclusionsThe non-linear inverse association of PTH with 25(OH)D supports the hypothesis that vitamin D deficiency contributed to elevated PTH in this population. Although 25(OH)D was associated with bone outcomes, the magnitude of the association was similar at 25(OH)D concentrations below and above 25nmol/L. PTH was inconsistently associated with bone outcomes, suggesting single measurements of PTH may not be a useful marker of bone health in this setting.Funding SourcesCanadian Institutes of Health Research.

Infant Feeding Method and Body Composition Differences at 6 Months

ObjectivesExplore how feeding method is related to distribution of fat and fat free mass in infants at 6 months of age.MethodsThis is a secondary data analysis of an RCT assessing prenatal DHA supplementation on infant growth. At 6 months of age, DXA measured infant body composition and distribution. Total body less head (TBLH) was used. Feeding method was collected by questionnaire. Infants were split into groups of breastfeeding (BF; n = 56), combo (C; n = 14), or formula feeding (F; n = 44). A 24-hour dietary recall was performed and NDSR was used to determine nutrient totals. Nutrients in breastmilk were homogenously estimated using the human milk option in NDSR, and a standard intake volume was assumed for those feeding directly from the breast. One-way ANOVA determined differences between the groups.ResultsBF infants consumed the lowest calories (BF: 557 ± 108; C: 785 ± 173; F: 753 ± 169; P < 0.01) and weighed less than F fed infants (7.73kg ± 0.87 vs 8.06kg ± 1.10 respectively; P < 0.05). However, BF infants consumed the highest percentage of calories from fat at 51.8% ± 3.7 (compared to C: 47.2% ± 4.7; F: 46.3% ± 3.8; P < 0.01) and had higher percentage body fat (%fat; BF: 38.5% ± 4.7 C: 32.8% ± 4.3; F: 35.9% ± 3.4) and central %fat (BF: 27.3% ± 4.8; C: 23.3% ± 4.3; F: 24.0% ± 3.9; all pairwise P < 0.01). BF infants had 0.14kg higher central and 0.32kg higher peripheral fat mass than combo (P < 0.05) but not formula feeders, although central fat mass between BF and F approached significance (mean difference 0.07kg; p = 0.054). Central fat-free mass was different between the BF and F groups only, with BF having 0.22kg lower fat-free mass (P < 0.01). There were no significant differences between the groups in peripheral fat-free mass.ConclusionsFeeding method at 6 months of age is related to body composition and distribution. Although breastfeeding infants weighed less and consumed less calories, they had higher total and central %fat.Funding SourcesThis project was supported by an NIH NIDDK R01 grant.

Novel Body Composition Approaches with DXA: Comparison with Classical Total Body Scans

Traditionally, total body (TB) DXA scans to assess body composition include the entire body, however novel abbreviated scan acquisition methods are available in new software. For example, total body less head (TBLH) is recommended given the head contains lean mass that cannot be altered by intervention. Recently, to reduce scan time and radiation exposure, a neck to knee (N-K) acquisition option is available. Finally, scans limited to the lower extremity might be useful to evaluate regional mass change after surgery/injury and in sarcopenia assessment. The purpose of this study was to evaluate comparability of measured and estimated body composition results using TBLH, N-K and lower extremity (LE; pelvis to toes) acquisition techniques. We hypothesized that body composition data with the 3 novel methods would not differ from the traditional TB method. Each subject had 4 scans: TB, TBLH, N-K and LE. A subset of 30 had repeat N-K and LE scans with repositioning between. A Lunar iDXA (GE, Madison, WI) with enCORE v18.0 was used to acquire and analyze scans. TB scans were acquired per ISCD guidance. TBLH and N-K scans were acquired using automated software features that limited the anatomy scanned; N-K estimates non-scanned leg mass. LE scans were started at L3 and auto stopped past the toes. Automated analysis, with manual correction, was used for all but LE scans which were analyzed manually by compressing all upper body ROIs above the pelvis then placing lower body ROIs at the top of pelvis, bisecting the femur neck and separating the legs. Pearson Correlation and Bias plots were used to compare regional lean, fat and BMC measurements from the 3 novel scans to TB. Precision determined by the ISCD Precision Calculator was compared to TB historical control by F-test. The study sample included 82 subjects, 41F/41M mean (SD) age 51.0 (18.4) years and BMI 25.5 (3.7) kg/m2. Mean lean, fat and bone mass were very similar among all approaches with some statistical, but likely not clinical, differences (Tables 1&3). Composition from all regions with the 3 novel methods was highly correlated with TB measurement, r=0.99-1.0, p< 0.001 with mean bias of 14-237g lean, 7-121g fat and 0.3-13.3g BMC (Table 2). N-K and LE precision was excellent ranging from 0.45-2.31 %CV (Table 3). These 3 novel approaches to either measure or estimate regional body composition are consistent with traditional TB measurement and may be considered as substitutes when appropriate.

Bone accrual and structural changes over one year in youth with cystic fibrosis

BackgroundPediatric bone accrual governs peak bone mass and strength. Longitudinal studies of bone health in youth with cystic fibrosis (CF) may provide insight into CF-related bone disease (CFBD), a prevalent co-morbidity in adults with CF. MethodsThis one-year longitudinal study of youth with pancreatic insufficient CF, enrolled in a nutrition intervention study [n = 62 (36 M/26F)] 1) examined dual-energy x-ray absorptiometry (DXA)-defined lumbar spine (LS) and total body less head (TBLH) bone accrual and 2) compared their changes in peripheral quantitative computed tomography (pQCT) cortical and trabecular tibial bone density and geometry to those of a healthy reference group [n = 143 (68 M/75F)].Main outcome measures were 1) DXA: lumbar spine areal bone mineral density (LSaBMD) and total body less head bone mineral content (TBLH-BMC), sex- and pubertal status-specific, height velocity (HV)-adjusted or HV and lean body mass velocity (HV-LBMV)-adjusted annualized velocity-Z scores and 2) pQCT: age, sex, pubertal status and, when appropriate, tibial length adjusted Z-scores for bone architecture measures.DXA velocity-Z were compared to expected mean of 0 and correlations with clinical parameters (age, BMI-Z and FEV1%-predicted) tested. Within-subject comparisons of HV-adjusted and LBMV-HV-adjusted DXA velocity-Z were conducted in CF.pQCT Z-scores were compared between the two groups over one year using longitudinal models. Longitudinal relationships between measures of bone health and clinical parameters (age, BMI-Z and FEV1%-predicted) were examined in individuals with CF. ResultsDXA velocity-Z were higher than normal in females (p < 0.05) but not males with CF. HV-adjusted and LBMV-HV-adjusted velocity-Z did not differ for LSaBMD or TBLH-BMC.In males with CF, both HV-adjusted and LBMV-HV-adjusted LSaBMD velocity-Z scores correlated negatively with age (HV rho: −0.35; p = 0.045 and LBMV-HV rho: −0.47; p = 0.0046). In males with CF BMI-Z correlated positively with HV-adjusted LSaBMD velocity-Z (rho: 0.37; p = 0.034), but this relationship did not persist for LBMV-HV (rho: 0.14; p = 0.42). In females with CF, no correlations between LSaBMD velocity-Z scores and age or BMI-Z were found (all p > 0.05). No correlations between LSaBMD velocity-Z scores and FEV1%-predicted were seen in either sex (all p > 0.12). TBLH-BMC velocity Z-scores were not correlated with clinical parameters in either sex (all p > 0.1).At baseline, multiple pQCT parameters were lower in CF (p < 0.05). pQCT Z-scores did not differ between baseline and one-year in either CF or reference group. In a longitudinal model comparing pQCT-Z changes in CF and reference, multiple pQCT-Z outcomes remained lower in CF, but the changes in parameters did not differ in CF vs reference (all p > 0.26). Lower pQCT outcomes in CF were largely restricted to males (CF group*female sex interaction beta coefficients > 0). In this combined longitudinal model, of both CF and reference, BMI-Z was positively associated with pQCT-Z parameters(p < 0.001).Multiple pQCT-Z outcomes positively correlated with both BMI-Z and FEV1%-predicted in males with CF, and with FEV1%-predicted in females with CF (p < 0.05). Age was negatively associated with section modulus (p = 0.001) in males and with cortical density-Z in females (p < 0.001). ConclusionsWith improved longevity, bone health in CF is of increasing importance. On average, bone accrual was preserved in youth with CF, and while deficits in bone geometry and strength were found, these deficits did not worsen over the one-year study. Lower LS bone accrual with increasing age suggests emerging adulthood is a period of vulnerability in CF while the role of LBM in bone health is underscored by the lack of relationship between LBMV-adjusted accrual and BMI. These findings may be useful in targeting screening practices and interventions.

Diagnostic Evaluation of the Functional Muscle-Bone Unit in Children With Cerebral Palsy With and Without Low Trauma Fractures

Children and adolescents with cerebral palsy (CP) are at increased risk of low trauma fractures (LTF) due to low bone mineral content (BMC). The risk of LTFs might be overestimated by only age – and sex adjusted Z-scores for BMC because Z-score based DXA techniques do not take into account other relevant parameters like height, muscle and fat mass. This study aimed to present an update of the functional muscle-bone unit-algorithm (uFMBU-A) to evaluate bone health in children with CP in order to predict the risk of LTF taking into account the parameters sex, age, height, muscle and fat mass. We performed a monocentric retrospective analysis of 177 DXA-scans of children and adolescents with CP aged 8–19. Six of these 177 patients had sustained at least 1 LTF. Age-, sex- and size adjusted Z-scores of total body less head (TBLH)-BMC, lean body mass and fat mass were calculated. The uFMBU-A was applied to the study group and results were compared with established Z-score based DXA-measurements and algorithm based diagnostic techniques concerning the prediction of LTF risk. The uFMBU-A had the greatest diagnostic odds ratio (13.3 [95% CI 2.41; 72.9]) of the evaluated predictors with a sensitivity of 50.0% (95% CI 11.8; 88.2), specifity of 93% (95% CI 88.1; 96.3). The uFMBU-A was the most accurate method of the evaluated parameters to predict LTF in children with CP and is recommended when evaluating bone health.

Effects of vitamin D and high dairy protein intake on bone mineralization and linear growth in 6- to 8-year-old children: the D-pro randomized trial

Vitamin D and dairy protein may stimulate bone mineralization and linear growth in children, but previous studies show inconsistent results and have not examined their combined effects. To investigate combined and separate effects of vitamin D supplementation and high-protein (HP) compared with normal-protein (NP) yogurt intake on children's bone mineralization and linear growth. In a 2×2-factorial trial, 200 healthy, 6- to 8-year-old, Danish, children with light skin (55°N) were randomized to 20µg/d vitamin D3 or placebo and to substitute 260g/d dairy with HP (10g protein/100g) or NP (3.5g protein/100g) yogurt for 24 weeks during an extended winter. Outcomes were total body less head (TBLH) and lumbar spine bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) by dual-energy X-ray absorptiometry, height, and biomarkers of bone turnover and growth. The primary outcome was TBLH BMD. In total, 184 children (92%) completed the study. The baseline serum 25-hydroxyvitamin D was 80.8±17.2nmol/L, which increased by 7.2±14.1nmol/L and decreased by 32.3±17.5nmol/L with vitamin D and placebo, respectively. The baseline protein intake was 15.4±2.4 energy percentage (E%), which increased to 18.3±3.4 E% with HP. There were no vitamin D-yogurt interactions and no main effects of either intervention on TBLH BMD. However, vitamin D supplementation increased lumbar spine BMD and TBLH BMC compared to placebo, whereas HP groups showed lower increments in lumbar spine BMD, TBLH BMC and BA, and plasma osteocalcin compared to NP groups. Height, growth factors, and parathyroid hormone levels were unaffected. Although there were no effects on whole-body BMD, vitamin D increased bone mass and spinal BMD, whereas high compared with normal dairy protein intake had smaller incremental effects on these outcomes. This supports a recommended vitamin D intake of around 20µg/d during winter but not use of HP dairy products for improved bone mineralization among healthy, well-nourished children. This trial was registered at clinicaltrials.gov as NCT03956732.

Bone density and body composition in small for gestational age children with adequate catch up growth: A preliminary retrospective case control study

Fetal growth patterns and birth weight (BW) have been associated with bone mineral density (BMD) and content (BMC) throughout infancy and childhood up to early adulthood. We hypothesized that in small for gestational age (SGA) children, compensatory infant catch-up growth to normal height centiles counteracts the adverse consequences of low BW on bone accrual. To evaluate BMD and BMC of SGA children born at term who experienced a normal catch-up growth as compared to children born appropriate for gestational age (AGA). We recruited 53 SGA (26 females) and 60 AGA children (27 females), aged 6 to 18years, matched for sex and body mass index (BMI). Fat mass (FM); Free fat mass (FFM); Lumbar spine and Total body less head (TBLH) BMD; BMC and BMD standard deviation scores corrected for body size (BMAD, BMAD z-score and TBLH BMD/Height) and TBLH BMC for FFM (TBLHBMC/FFM) were derived from Dual Energy X-ray absorptiometry (DXA) scans. SGA and AGA children did not differ in any auxological, body composition and bone parameters appropriately adjusted for height and FFM. BMI, FM and, remarkably, FFM were significantly correlated with bone mass parameters in both groups while no correlation was found between FM and FFM with the BW SDS in the univariate analysis. Our preliminary data demonstrate that SGA children born at term who recover from their growth deficiency through catch-up growth achieve bone mass and body composition not different from children born AGA.

P013 Serum osteoprotegerin and RANKL in patients with Juvenile Idiopathic Arthritis and their correlation with bone mineral density

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic arthropathy of childhood and is associated with low bone mass, and may hasten the onset of osteoporosis later in life1. Bone loss occurs because of an imbalance between osteoclasts-activating factors like receptor activator of nuclear factor-κB ligand (RANKL) and its inhibitor osteoprotegerin (OPG) 2. Dual energy X-ray absorptiometry (DXA) is the preferred method for measuring bone mineral density (BMD) in children and to identify and follow individuals at risk for fracture 3. The objective is the Evaluation of serum levels of osteoprotegerin and RANKL and their correlation with BMD in JIA patients. Methods Forty JIA patients (according to the revised classification criteria of ILAR) and 40 healthy children individually matched for age, sex and race were included in this study. Children excluded from the study were those with primary and secondary causes of osteoporosis (such as chronic illness). All patients were assessed clinically by: age, sex, body mass index, type of JIA, disease duration and disease activity (by Juvenile Arthritis Disease Activity Score; JADAS 10). The functional disability was assessed by the Childhood Health Assessment Questionnaire (CHAQ). Blood samples were collected from JIA patients and healthy controls to determine serum levels of OPG and RANKL by ELISA. DXA scans were done using GE Healthcare Lunar DPX, Madison, Wisconsin. Bone mineral density of the L1-L4 lumbar spine and total body less head (TBLH) was evaluated in g/cm2 and expressed as Z score for age, sex according to the reference data given for this equipment. Results The study included 40 patients (25 females) with a mean age of 11.14 years and median disease duration of 2.5 years. As regard JIA type, 45% of patients were oligoarticular, 32.5% were polyarticular, and 22.5% were systemic JIA. Median JADAS 10 was 13.95. Patients (especially polyarticular JIA) had significantly higher serum RANKL levels and lower serum OPG and OPG/RANKL ratio when compared with controls (with p-value &amp;lt;0.001, 0.032 and &amp;lt;0.001 respectively). A diagnosis of low BMD (BMD Z-score ≤ -2) was given in 25% of patients (15% polyarticular and 10% systemic) by DXA of lumbar spine, and 20% (10% polyarticular and 10% systemic) by DXA of TBLH. On the other hand, no patient was given a diagnosis of osteoporosis (BMD Z-score ≤ -2 and a significant fracture history). Low BMD at lumbar spine and TBLH was negatively correlated with serum RANKL while positively correlated with OPG/RANKL ratio. Moreover, low BMD at lumbar spine was positively correlated with serum OPG level Conclusion High RANKL and low OPG levels appear to be associated with low bone mass in JIA patients. Patients with JIA (especially polyarticular and systemic subtype) are at increased risk of low bone mineral mass. Disclosure of Interests None declared

Evaluation of anthropometry as an alternative to DXA as predictor of low bone mineral density in children and adolescents with cystic fibrosis.

Low bone mineral density (BMD) for age in people with Cystic Fibrosis (CF) is associated with worse nutritional status. The aim of this study is to assess body composition by anthropometry as a predictor of BMD in people with CF. Multicenter cross-sectional study with 39 people aged 5 and 20 years with CF. BMD was assessed by dual energy x-ray emission (DXA) in the incidence of the total body less head (TBLH) and the TBLH Z-score (Z-TBLH) was calculated, adjusted by sex, age, height and ethnicity. Anthropometry was assessed by weight, height, mid-upper arm circumference (MUAC) and triceps skinfold (TSF). Arm muscle area (AMA) and Body Mass Index (BMI) were calculated. Lean mass (LM), fat mass (FM) and free-fat mass (FFM) were identified by DXA. The molecular analysis method by sequencing was used to identify and classify the participants regarding the presence of the F508del pathogenic variant of the CFTR gene. Statistical models of simple and multiple linear regression were created to establish the predictive power of Z-TBLH in the variables. Average age of the participants was 13.31±3.86 years, 59% of whom were male. They showed more LM (30.97Kg±11.29) than females (23Kg±6.73). 20 of 30 participants (66.7%) had at least copy of F508del. Among the multiple models, adjusted by height, age and sex, it found BMI (R2=0.367), Weight (R2=0.220), AMA (R2=0.338) as significant predictors of Z-TBLH. The final model composed of AMA, TSF and Age (p=0.001; R2=0.381) had AMA and Age as significant predictors. AMA was associated with an increase in the BMD Z-score in the participants studied. 66.7% of genetically tested participants had the F508del pathogenic variant. The presence of the F508del variant was associated with worse nutritional status. A statistical model composed of the values of AMA, TSF and Age can predict Z-TBLH, as well as anthropometric variables Weight, or BMI, or AMA associated with height, age and sex, in children and adolescents aged 5-20 years old, of both sexes. Anthropometric markers, as they are easy and relatively inexpensive to obtain, it is a promising alternative to the use of DXA in predicting BMD in these people with CF.

Case Report: Low Bone and Normal Lean Mass in Adolescents With Complete Androgen Insensitivity Syndrome

IntroductionOsteopenia and osteoporosis have been reported in adults with Complete Androgen Insensitivity Syndrome (CAIS). Little is known about changes in bone mineral density (BMD) in adolescents with CAIS and whether it is affected by early gonadectomy. Body composition data have not been reported.MethodsSingle-center, retrospective study of CAIS adolescents who underwent dual-energy x-ray absorptiometry (DXA) (Hologic, Horizon A). Body composition is presented as lean and fat mass indices (LMI, FMI). Z-scores for lumbar spine areal BMD (LBMD), total body less head (TBLH), bone mineral content (BMC), LMI, and FMI were calculated using female normative data. Results are expressed as median and min, max.ResultsSix females with genetically confirmed CAIS were identified—one with intact gonads and five with history of gonadectomy at 2–11 months. In the subject with intact gonads, LBMD-Z and TBLH BMC-Z were −1.56 and −1.26, respectively, at age 16 years. Among those with gonadectomy, LBMD-Z was −1.8 (−3.59 to 0.49) at age 15.6 years (12–16.8) and decreased in all three subjects who had longitudinal follow-up despite hormone replacement therapy (HRT). Adherence to HRT was intermittent. LMI-Z and FMI-Z were 0.1 (−1.39 to 0.7) and 1.0 (0.22 to 1.49), respectively.ConclusionsThese limited data indicate that adolescents with CAIS have bone mass deficit. Further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual. Data on lean mass are reassuring.

Bone mineral density and its influencing factors in Chinese children with spinal muscular atrophy types 2 and 3

BackgroundPatients with spinal muscular atrophy (SMA) are at risk of decreased bone mineral density (BMD). The bone health status of Chinese patients with SMA has been poorly studied. We aimed to evaluate the BMD of children with SMA types 2 and 3 in mainland China and investigate its influencing factors.MethodsForty patients with a mean age of 5.5 years affected by SMA types 2 and 3 (n = 22 and n = 18, respectively) were enrolled between September 2017 and May 2019. Total body less head (TBLH) BMD, lumbar spine (LS) BMD, and body composition were measured using dual-energy X-ray absorptiometry (DXA). Serum bone metabolism markers and complete spinal radiographs were assessed. We utilized a linear regression model to explore the correlations between BMD and its related factors.ResultsA total of 67.5% (27/40) of patients were diagnosed with low BMD and 2.5% (1/40) were diagnosed with osteoporosis. The TBLH BMD and LS BMD Z-scores in children with SMA type 2 were significantly lower than those with SMA type 3. Both TBLH and LS BMD Z-scores tended to increase with the change of SMA subtypes from 2a-3b. Vitamin D insufficiency and deficiency were found in 37.5% (15/40) of the patients. Serum Ca, phosphorus (P), alkaline phosphatase (ALP) and parathormone (PTH) levels were normal. There were no significant differences among the four subtypes in terms of all the serum bone metabolism markers. Phenotype was significantly associated with TBLH BMD and LS BMD Z-scores, and serum PTH levels were significantly associated with TBLH BMD Z-scores.ConclusionsLow BMD and osteoporosis were highly prevalent in mainland Chinese children with SMA types 2 and 3. Phenotype and serum PTH level might be the influencing factors of BMD. Regular monitoring of BMD by DXA scan and taking active interventions aim to SMA children with different types are important.

Uncoupling of Bone Turnover may Compromise Skeletal Health of Young Patients With Haemophilia A

There is evidence that bone mass is decreased and bone metabolism is dysregulated in children with haemophilia (CWH). The objective of this study was to investigate the impact of haemophilia on skeletal health in children, with regards to bone mineral density (BMD) and metabolic bone profile. This study included 51 male CWH A. Dual-energy X-ray absorptiometry (DXA) was performed to assess BMD in lumbar spine (LS) and total body less head (TBLH) and Z-scores were calculated (low BMD Z-score<-2, low-normal BMD Z-score between -1 and -2). Serum levels of osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), bone alkaline phosphatase (bALP), bone tartrate-resistant acid phosphatase 5b (TRAP5b), vitamin D, parathormone (PTH), urinary calcium/creatinine (uCa/uCr) and urine deoxypyridinoline/creatinine (uDPD/uCr) were measured. Mean BMD Z-scores were lower than predicted at both sites of measurement. More specifically, 10% of CWH A had low and 20% low-normal BMD Z-scores in LS, whereas 9.1% had low-normal TBLH BMD Z-scores and there were no patients with low BMD Z-scores at this site of measurement. 36.7% of CWH had low vitamin D levels and 19.6% had a history of fracture. Also, patients with haemophilia had lower OC and higher uDPD/uCr levels while OC positively correlated to BMD Z-scores and uDPD/uCr negatively correlated to BMD Z-scores at both sites. No statistically significant differences were observed with regards to mode of treatment, number of haemorrhages and the presence of target-joints. CWH A had decreased BMD Z-scores at both sites with an uncoupling of bone turnover LS BMD seemed to be more affected than TBLH BMD.

Moderate-to-Vigorous Physical Activity Is Associated With Higher Bone Mineral Density in Children With Inflammatory Bowel Disease.

Decreased mineral bone density (BMD) and reduced lean body mass (LBM) are common amongst children with inflammatory bowel disease (IBD). The aim of our cross-sectional, observational study was to evaluate the relationship between BMD, body composition and physical activity (PA) in children with IBD in remission. Total body less head (TLBH) dual energy X-ray absorptiometry (DXA) was used to measure BMD, fat mass (FM) and lean body mass (LBM). Triaxial accelerometer for five consecutive days was used to objectivize PA. Forty pediatric IBD patients in clinical remission (24 boys; age 15.3 ± 0.4 years; Crohn disease [CD], n = 20, ulcerative colitis [UC], n = 18, inflammatory bowel disease-unclassified [IBD-U], n = 2) were recruited. Mean BMD was 0.940 g/cm2 and mean BMD z score was -0.42 ± 0.14. Patients with CD had significantly lower BMD than UC counterparts (P < 0.001). Average time spent in PA was 247.24 ± 16.71 min/day with 45.73 ± 8.22 min/day spent in moderate-to-vigorous PA (MVPA). We observed a significant positive correlation between the time spent in MVPA and BMD z score (P = 0.003) and LBM z score (P = 0.026). Multivariate analysis confirmed that the positive correlation of MVPA and BMD z score. There was no significant correlation between daily protein intake and BMD. Cumulative glucocorticoid dose negatively correlated with LBM z score (P = 0.003), but not with BMD z score (P = 0.069). This study points to a strong positive relationship between MVPA, LBM and BMD. Longitudinal studies are required in order to elucidate the modifiable processes that determine body health and favorable body composition.

Does the severity of obesity influence bone density, geometry and strength in adolescents?

Relationships between the severity of obesity and bone health remain underexplored. To compare whole-body and localized bone mineral content (BMC) and density (BMD), trabecular bone score (TBS) and hip geometry and strength between adolescents with obesity versus extreme obesity. This cross-sectional study included 154 adolescents (12-15 years, 62% females) who were classified as having obesity (OG, [95th-99th] percentile) or extreme obesity (EOG, >99th percentile). Fat mass (FM), lean mass (LM), BMC, BMD for total-body-less-head (TBLH), lumbar spine (LS), hip, TBS and geometric and strength indices at the narrow-neck (NN), femoral shaft (FS) and intertrochanteric regions (IT) were assessed by Dual-X-ray Absorptiometry (DXA). There was no significant sex-interaction. For both sexes, TBLH BMC and BMD were not different between groups. TBS was lower in EOG compared with OG in both sexes in univariate analysis and after adjustment with maturation and body weight (p < 0.05). Hip BMD was significantly higher in the EOG compared to OG only after adjustment with maturation and fat mass percentage (p < 0.05 for men, p < 0.01 for women). For both sexes, TBLH, LS and hip BMC and BMD positively correlated with weight, BMI, LM and FM. TBS negatively correlated with BMI-percentile in both sexes, with a negative correlation with FM for males alone. Hip BMC and BMD, BMD, ACT and CSA at the three hip sites positively correlated with BMI-percentile in males. Extreme obesity impacts bone health depending on anatomical sites, altering lumbar trabecular bone in both males and females adolescents.

The associations of gut microbiota and fecal short-chain fatty acids with bone mass were largely mediated by weight status: a cross-sectional study.

We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with bone mass in healthy children aged 6-9years. In this study, 236 healthy children including 145 boys and 91 girls were enrolled. 16S rRNA gene sequencing was used to characterize the composition of their gut microbiota. Total and 10 subtypes of SCFAs in the fecal samples were determined by high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the bone mineral density (BMD)and bone mineral content (BMC) for total body(TB) and total body less head (TBLH).Z score of TBLH BMD was calculated based on therecommended reference. Four gut microbiota principal components (PCs) were identified by the compositional principal component analysis at the genus level. After adjustment of covariates and controlling for the false discovery rate, multiple linear regression analysis showed that PC3 score (positive loadings on genera Lachnoclostridium andBlautia) was significantly negatively associated with TBLH BMD/BMC/Z score, TB BMC and pelvic BMD (β: -0.207 to-0.108, p: 0.002-0.048), whereas fecal total and several subtypes of SCFAs were correlated positively with TBLH BMD/Z score and pelvic BMD (β: 0.118-0.174, p: 0.038-0.048). However, these associations disappeared after additional adjustment for body weight. Mediation analysis suggested that body weight significantly mediated 60.4% and 78.0% of the estimated association of PC3 score and SCFAs with TBLH BMD Z score, respectively. The associations of gut microbiota composition and fecal SCFA concentrations with bone mass in children were largely mediated by body weight.

Effect of Maternal Prenatal and Postpartum Vitamin D Supplementation on Offspring Bone Mass in Early Childhood: Follow-Up of a Randomized Controlled Trial

ObjectivesMaternal vitamin D status has gained substantial attention as a modifiable contributor to offspring musculoskeletal health, yet there is a paucity of trial-derived data to corroborate effects of prenatal or postpartum vitamin D supplementation on offspring bone mass accrual. Among maternal-infant pairs in Bangladesh, we aimed to examine the hypothesized causal association of early life vitamin D exposure with musculoskeletal health in childhood. MethodsIn a double-blind dose-ranging trial of maternal vitamin D3 supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) were recruited at 17–24 weeks’ gestation and randomly assigned to receive a prenatal; postpartum regimen of 0;0,4200;0,16,800;0,28,000;0 or 28,000;28,000 IU vitamin D3/week until 26 weeks postpartum. In a follow-up study of offspring at 4 years of age (n = 642), bone mineral content (BMC) and bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry. Between-group differences were assessed by independent t-tests (28,000 IU/week prenatally vs placebo) and linear regression (each vitamin D treatment group vs placebo) with bootstrapping (1000 replications). ResultsWhole-body (WB), total-body-less-head (TBLH) and head-only BMC were similar in the combined high-dose prenatal and placebo groups (mean difference [95% CI] = 6.81g [–8.70, 22.32], 0.61g [–10.90, 12.13] and 1.71g [–3.54, 6.96], respectively). None of the mean values for WB or TBLH BMC or BMD in each vitamin D group were different from placebo (P > 0.05 for all comparisons). Although head BMD was slightly greater in offspring of women assigned to the 28,000;28,000 IU regimen compared to placebo (mean difference [95% CI] = 0.024g/cm2 [0.0009, 0.047], P = 0.042), the effect was attenuated and no longer significant upon adjustment for child height, weight, and sex (P = 0.11). ConclusionsIn a population with high prevalence of vitamin D deficiency, our findings do not support the use of maternal prenatal vitamin D supplementation, with or without postpartum supplementation, for improvement of child BMC or BMD at 4 years of age. Funding SourcesCanadian Institutes for Health Research and the Bill and Melinda Gates Foundation.

The Positive Relationship between Moderate-to-Vigorous Physical Activity and Bone Mineral Content Is Not Mediated by Free Leptin Index in Prepubertal Children: The PANIC Study.

Purpose: Moderate-to-vigorous physical activity (MVPA) positively influences bone mineral content (BMC) in prepubertal children, but it is unknown whether this relationship is partially mediated by free leptin index. The aim of this study was to examine whether the relationship between MVPA and total body less head (TBLH) BMC is mediated or moderated by free leptin index in prepubertal children. Methods: We performed a cross-sectional analysis on 401 children (194 girls) from baseline examinations of the Physical Activity and Nutrition in Childhood Study. We applied the four-way decomposition mediation analysis method to assess whether free leptin index, measured from fasted blood samples, mediated the relationship between accelerometer-measured MVPA and TBLH BMC measured by dual-energy X-ray absorptiometry. Results: MVPA had a positive controlled direct effect on TBLH BMC in girls and boys (β = 0.010 to 0.011, p < 0.05). There was no mediation or interaction between MVPA, free leptin index and TBLH BMC in girls or boys (β = −0.000 to 0.001, p > 0.05). Conclusion: Our study indicates that MVPA positively influences TBLH BMC through pathways not related to free leptin index in predominantly normal-weight prepubertal children, likely primarily through mechanical loading. The relationships between MVPA, free leptin index and TBLH BMC may be influenced by other factors such as pubertal status and adiposity, so it is unknown whether these observations extend to overweight and obese children at different stages of puberty.

Bone Health in Pediatric Patients With Crohn Disease.

The aim of our study was to examine longitudinal changes in bone mineral density (BMD) of children and adolescents with Crohn disease (CD), and risk factors related to low BMD. All patients ages from 2 to 18 years with CD who underwent dual-energy X-ray absorptiometry (DXA) at diagnosis and at the end of follow-up between 1999 and 2018 were considered for inclusion in this retrospective study. Factors related to changes in BMD at diagnosis and during follow-up were investigated. One hundred and ninety-three patients had the two DXA required. At diagnosis, 36 patients (18.7%) had a low BMD.At the end of follow-up, 31 patients (16%). One hundred and sixty-four patients did not have the two DXA required.In included CD, BMD values were lower in the lumbar spine (LS) than in total body less head (TBLH), as well at diagnosis (P < 0.0001) or at the end of follow-up (P = 0.001).At diagnosis, only growth impairment or low BMI was associated with low BMD (P < 0.0001), only cumulative dose of corticosteroid at the end of follow-up (P = 0.01). The high prevalence of low BMD in children and adolescents with IBD highlights the importance of evaluating BMD in these patients at the time of diagnosis and throughout the course of their treatment. Special attention must be given to patients with height delay or low BMI at diagnosis. Long-term glucocorticoid therapy is the main clinical risk factor associated with low BMD at the end of follow-up.

Bone mineral density at age 7 years does not associate with adherence to vitamin D supplementation guidelines in infancy or vitamin D status in pregnancy and childhood: an Odense Child Cohort study.

Vitamin D supplementation in infancy is recommended to prevent rickets. At the population level, its effects on bone mineralisation are largely unknown. We aimed to explore whether adherence to national vitamin D supplementation guidelines (10 µg/d up to the age of 2 years), supplementation at the ages of 5 and 7 years, and serum 25-hydroxyvitamin D (s-25(OH)D) at various time points associated with bone mineral density (BMD) at the age of 7 years in the Odense Child Cohort, Denmark (n 1194). High adherence was defined as supplementation with 10 µg of vitamin D 6-7 times per week during ≥80 % of the observation time. s-25(OH)D was analysed using LC-MS/MS. Total-body-less-head (TBLH) BMD was measured by dual-energy X-ray absorptiometry. At the median age of 18·1 months, 53·9 % (n 475/881) reported high adherence. The median s-25(OH)D was 64·7, 78·8, 46·0 and 71·8 nmol/l in early pregnancy, late pregnancy, cord blood and at 5 years, respectively. The mean TBLH BMD at the median age of 7·1 years was 0·613 (SD 0·049) g/cm2 (z-score +0·363 (SD 0·824)). In adjusted analyses, vitamin D supplementation up to 18 months, and at 5 and 7 years, was not associated with TBLH BMD. Similarly, no robust associations were found between TBLH BMD and s-25(OH)D at any time point. No associations were found for TBLH bone mineral concentration or bone area. In this population with relatively high s-25(OH)D concentrations, no consistent associations were found between adherence to vitamin D supplementation recommendations or vitamin D status in pregnancy or childhood, and bone mineralisation at the age of 7 years.