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Background: Body fat percentage (BF%), fat mass index (FMI), and lean body mass index (LBMI) are often used to evaluate the nutritional status of children. Until now, no pediatric FMI reference centiles are applicable for GE Healthcare Lunar DXA systems. The aim of the study was to generate age-specific BF%, FMI, and LBMI references centiles for GE Healthcare Lunar DXA systems. Methodology: Published values from the National Health and Nutrition Examination Survey 1999–2004 (age 8–20 years) were used to generate the reference centiles for the non-Hispanic black, non-Hispanic white, and Mexican American NHANES population. The LMS and LMSP methods were used to generate the reference centiles. Results: Data of 2433 non-Hispanic black children (972 females), 2026 non-Hispanic white children (873 females), and 2547 Mexican American children (1010 females) were eligible. Conclusions: We presented age-specific reference centiles for BF%, FMI, and LBMI for children and adolescents which were ethnicity specific (non-Hispanic black, non-Hispanic white, and Mexican American) and directly applicable to Prodigy and iDXA GE Healthcare Lunar systems with software version 14.0. We proposed the use of BF%, FMI, and LBMI together to evaluate nutritional status in children.

Bone strength and fracture risk do not only depend on bone density, but also on bone structure. The trabecular bone score (TBS) evaluates homogeneity of bone microarchitecture indirectly by measuring gray-level variations of two-dimensional (2D) DXA images. Although TBS is well-established for adults, there have been only few publications in pediatrics. In this monocentric retrospective analysis, we investigated TBS in children and adolescents with cerebral palsy (CP), a patient group vulnerable to low bone mineral mass due to impaired mobility. The influence of different parameters on TBS and areal BMD (aBMD) were evaluated, as well as the relationship between TBS and aBMD. We compared TBS values of our study population to a reference population. A total of 472 lumbar spine-dual-energy X-ray absorptiometry (LS-DXA) scans of children and adolescents with CP (205 female), aged between 4 and 18 years, were analyzed. The DXA-scans were part of the routine examination. The children had no records of fractures or specific bone diseases. Our study population with CP had similar TBS as the reference population. TBS did not increase with age until an inflection point at 10 years in females, and 12 years in males. Girls had significantly higher TBS than boys (p = .049) and pubertal girls aged 8 to 13 years had significantly higher TBS than prepubertal girls (p = .009). TBS standard deviation score for age (SDS-TBS) and aBMD Z-scores correlated weakly (p < .001; R = 0.276 [males], R = 0.284 [females]). Other than for aBMD Z-scores, SDS-TBS was not influenced by age-adjusted height Z-scores and there was no significant difference in SDS-TBS when grouped by mobility levels, using the Gross Motor Function Classification System (GMFCS). Our results indicate that children with CP have a similar homogeneous distribution of trabecular microarchitecture as controls. Puberty initiation appears to be essential for increase of TBS with age and for sex differences. TBS seems less influenced by body composition, height, and mobility than aBMD. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Zusammenfassung Die Osteogenesis imperfecta (OI) ist eine angeborene Erkrankung des Knochens und Bindegewebes. Sie geht mit einer erhöhten Frakturneigung, Deformierung der Extremität, aber auch mit extraskelettalen Symptomen einher. Nach einer kurzen Darstellung von Klinik, Diagnostik und aktueller Therapie folgt ein umfassender Überblick über die genetischen und pathophysiologischen Grundlagen der Erkrankung und die daraus abgeleiteten zukünftigen therapeutischen Möglichkeiten. Ungefähr 80 % der Patienten haben eine Mutation in den Kollagen-Genen COL1A1 und COL1A2. Bei diesen Patienten ist für das Kollektiv keine klare Genotyp-Phänotyp-Korrelation beschrieben. Stoppmutationen führen in der Regel zu einem quantitativen Kollagendefekt, wodurch weniger normales Kollagen gebildet wird und ein eher leichter Phänotyp entsteht. Missense-Mutationen führen zu strukturell verändertem Kollagen (qualitativer Defekt) und zu einem schwereren Phänotyp. Trotzdem gibt es Unterschiede und Vorhersagen über den individuellen Verlauf sind nur sehr eingeschränkt möglich. Neben Veränderungen in den Kollagen-Genen gibt es Mutationen, welche die Kollagenmodifikation und die Kollagensekretion betreffen. Eine eigene Gruppe bilden Gene, welche an der Osteoblastendifferenzierung beteiligt sind. Wie auch bei den weiteren, nicht näher zugeordneten Genen sind dies häufig übergeordnete Gene, deren Funktion in der Osteogenese nicht völlig verstanden ist. Abgeleitet aus den pathophysiologischen Grundlagen, können vorhandene Medikamente zukünftig womöglich zielgerichtet eingesetzt werden. So ist der „Receptor-Activator-of-Nuclear-Factor-Kappa B-Ligand“ (RANKL)-Antikörper Denosumab spezifischer als Bisphosphonate und wird schon heute bei OI-Typ VI (SERPINF1) verwendet. Weitere Medikamente wie Anti-Sklerostin oder Stammzelltherapien werden unter Berücksichtigung der Pathophysiologie aktuell entwickelt.

Osteogenesis imperfecta is a hereditary connective tissue disorder, resulting in low bone mass and high bone fragility. Dual-energy X-ray absorptiometry (DXA) and in adulthood also the trabecular bone score (TBS) are well established to assess bone health and fracture risk. The purpose of this investigation was to assess the usefulness of TBS in respect to different treatment regimes in children with osteogenesis imperfecta. Changes of areal bone mineral density (aBMD) and TBS using DXA scans of children treated with antiresorptive therapies were evaluated.DXA scans (aBMD, TBS) of 8 children with OI were evaluated. The scans were taken during a 1 yr period of treatment with bisphosphonates and during 1 yr pilot trial using denosumab. Changes of aBMD and TBS during both treatment regimens were compared.During bisphosphonate treatment aBMD increased about 6.2%, while TBS increased about 2.1%. The difference between aBMD and TBS before and after bisphosphonate treatment was not significant (p = 0.25). During denosumab treatment aBMD increased around 25.1%, while TBS increased 6.7%. The change of aBMD was significant (p = 0.007), as was the difference between aBMD and TBS (p0.001).Denosumab had a significant effect on both aBMD and TBS but was significantly more pronounced in aBMD. These results suggest a stronger effect of denosumab on cortical bone and the growth plate in comparison to bisphosphonates. Beside the lack of paediatric reference data and the small sample size, the results suggest TBS to be a useful tool for monitoring skeletal changes during development, growth, and antiresorptive therapy in children with OI.

Objectives Obesity has often been associated with high low-density-lipoprotein cholesterol (LDL-C) and triglyceride plasma concentrations, known risk factors for diabetes mellitus and cardiovascular disease. Study objective was to evaluate the association of LDL-C and triglyceride plasma concentration with muscle and fat mass in children and adolescents. Methods We analyzed data of the National Health and Nutrition Examination Survey (1999–2004) to estimate lean muscle and fat mass assessed by dual-energy X-ray absorptiometry (DXA) of participants whose lipid profiles had been examined. Fat mass was operationalized by DXA-determined fat mass index (FMI). Muscle mass was assessed by appendicular lean mass index (aLMI). High LDL-C and triglyceride concentration was defined as above 130 mg/dL. Results For the evaluation of the association of LDL-C and triglyceride plasma concentration with LMI and FMI Z-scores, the data of 2,487 children and adolescents (age 8–19 years) (984 females) were eligible. High aLMI showed no association with LDL-C or triglyceride concentration, but high FMI showed significant association with LDL-C and triglyceride plasma concentration in the bivariate regression analysis. Conclusions Isolated muscle mass increase may not be protective against high LDL-C and triglycerides plasma levels in children and adolescents. Thus, exercise may lead to risk factor reduction mainly through fat mass reduction.

Objectives In children with cerebral palsy (CP), the most common cause of physical impairment in childhood, less muscle and bone growth has been reported, when compared with typically developing children. The aim of this study was to evaluate the effect of an intensive rehabilitation program including physiotherapy in combination with 6 months of home-based, vibration-assisted training on muscle and bone growth in children with CP. Methods We included children with CP, who participated in a rehabilitation program utilizing whole-body vibration (WBV). Muscle mass was quantified by appendicular lean mass index (App-LMI) and bone mass by total-body-less-head bone mineral content (TBLH-BMC) assessed by Dual-energy X-ray absorptiometry (DXA) at the beginning of rehabilitation and one year later. To assess the functional muscle-bone unit, the relation of TBLH-BMC to TBLH lean body mass (TBLH-LBM) was used. Results The study population included 128 children (52 females, mean age 11.9 ± 2.7). App-LMI assessed in kg/m2 increased significantly after rehabilitation. The age-adjusted Z-score for App-LMI showed no significant change. TBLH-BMC assessed in gram increased significantly. The Z-scores for TBLH-BMC decreased lesser than expected by the evaluation of the cross-sectional data at the beginning of rehabilitation. The parameter T B L H − B M C T B L H − L B M $\frac{TBLH-BMC}{TBLH-LBM}$ did not change relevantly after 12 months. Conclusions Muscle growth and to a lesser extent bone growth could be increased in children with CP. The intensive rehabilitation program including WBV seemed to have no direct effect on the bone, but the observed anabolic effect on the bone, may only been mediated through the muscle.

Background: Obesity was often associated with low high-density lipoprotein (HDL) cholesterol concentration, which is an established cardiovascular risk factor. Objectives: To evaluate the association of HDL-cholesterol concentration with fat and muscle mass in children and adolescents. Methods: Data of the National Health and Nutrition Examination Survey (1999-2004) were used to estimate fat and muscle mass by dual-energy X-ray absorptiometry (DXA) of the participants who had also an examination of their lipid profiles. Fat mass was assessed by DXA-determined fat mass index (FMI). Muscle mass was operationalized by appendicular lean mass index (LMI). Low HDL-cholesterol concentration was defined as Results: For the evaluation of the association of HDL-cholesterol concentration with FMI and LMI Z-scores, the data of 6288 children and adolescents (age 8-19 years) (2535 females) were eligible. In the study population, the prevalence of low HDL-cholesterol concentration increased with rising FMI and appendicular LMI Z-scores. Conclusions: The study results suggested that there is a counterintuitive, inverse association of muscle mass and HDL-cholesterol concentration.

Background Osteogenesis imperfecta (OI) is a rare disease leading to hereditary bone fragility. Nearly 90% of cases are caused by mutations in the collagen genes COL1A1/A2 (classical OI) leading to multiple fractures, scoliosis, short stature and nonskeletal findings as blue sclera, hypermobility of joints, bone pain and delayed motor function development. Bisphosphonates are used in most moderate and severely affected patients assuming that an increase of bone mineral density might reduce fractures and bone pain in patients with OI. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. First data from small clinical trials promised a high efficacy of Denosumab in children with OI. Aim of this analysis was a retrospective evaluation of an individualized biomarker-associated treatment regime with Denosumab in 10 children with classical OI which were followed for 1 year after their participation in a pilot trial with Denosumab. Therefore urinary deoxypyridinoline levels were evaluated frequently as an osteoclastic activity marker and depending on that levels Denosumab injections were scheduled individually. Methods Ten patients (age range: 6.16–12.13 years; all participated in the former OI-AK phase 2 trial (NCT01799798)) were included in the follow-up period. Denosumab was administered subcutaneously depending on the individual urinary excretion course of deoxypyridinoline (DPD/Crea) as osteoclastic activity marker with 1 mg/kg body weight. DPD/Crea levels were evaluated before denosumab administration and afterwards. If patients present after an initial decrease after injection with a re-increase up to the DPD/crea level before Denosumab injection next dosage was planned. Changes of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 12 month was evaluated. Safety was assessed by bone metabolism markers and side effect reporting. Results During follow-up mean relative change of lumbar aBMD was − 6.4%. Lumbar spine aBMD z-Scores decreased from − 1.01 ± 2.61 (mean ± SD) to − 1.91 ± 2.12 (p = 0.015). Mobility changed not significantly (GMFM-88 -6.49 ± 8.85% (p = 0.08). No severe side effects occurred. Dose intervals could be extended in the mean from 12 weeks previously to 20.3 weeks. Conclusions On average, it was possible to prolong the intervals between drug administrations and to reduce the total dose about by 25% without a decrease of mobility or change of vertebral shape despite a reduction of lumbar aBMD during 1 year of biomarker-directed Denosumab treatment. Further trials are necessary to balance side effects and highest efficacy in children.

SummaryThe interaction of body fat percentage and height with appendicular BMC for LBM was analyzed. Only body fat had significant negative correlation with the appendicular BMC for LBM.Purpose/introductionFor the clinical evaluation of the functional muscle-bone unit, it was proposed to evaluate the adaptation of the bone to the acting forces. A frequently used parameter for this is the total body less head bone mineral content (TBLH-BMC) determined by dual-energy X-ray absorptiometry (DXA) in relation to the total body lean body mass (LBM). Body fat percentage seemed to correlate negatively and height positively with TBLH-BMC for LBM. It was supposed that appendicular BMC for LBM is a more accurate surrogate for the functional muscle-bone unit since appendicular LBM does not incorporate the mass of internal organs. The aim of this study was to analyze the interaction of body fat percentage and height with appendicular BMC for LBM.MethodsAs part of the National Health and Nutrition Examination Survey (NHANES) study, between the years 1999 and 2004, whole-body DXA scans on randomly selected Americans from 8years of age were carried out. From all eligible DXA scans, three major US ethnic groups were evaluated (non-Hispanic Whites, non-Hispanic Blacks, and Mexican Americans) for further statistical analysis.ResultsFor the statistical analysis, the DXA scans of 8190 non-Hispanic White children and adults (3903 female), of 4931 non-Hispanic Black children and adults (2250 female), and 5421 of Mexican American children and adults (2424 female) were eligible. Only body fat had a significant negative correlation with the appendicular BMC for LBM.ConclusionsOnly body fat had significant negative correlation with appendicular BMC for LBM, and thus, should be addressed when evaluating functional muscle-bone unit.

Increasing knowledge in the field of rare diseases has led to new therapeutic approaches in the last decade. Treatment strategies have been developed after elucidation of the underlying genetic alterations and pathophysiology of certain diseases (e.g., in osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva). Most of the drugs developed are specifically designed agents interacting with the disease-specific cascade of enzymes and proteins involved. While some are approved (asfotase alfa, burosumab), others are currently being investigated in phase III trials (denosumab, vosoritide, palovarotene). To offer a multi-disciplinary therapeutic approach, it is recommended that patients with rare skeletal disorders are treated and monitored in highly specialized centers. This guarantees the greatest safety for the individual patient and offers the possibility of collecting data to further improve treatment strategies for these rare conditions. Additionally, new therapeutic options could be achieved through increased awareness, not only in the field of pediatrics but also in prenatal and obstetric specialties. Presenting new therapeutic options might influence families in their decision of whether or not to terminate a pregnancy with a child with a skeletal disease.

Background: Densitometrically measured lean body mass (LBM) is often used to quantify skeletal muscle mass in children with cerebral palsy (CP). Since LBM depends on the individual's height, the evaluation of LBM/height(2) (lean BMI) is often recommended. However, LBM includes not only skeletal muscle mass but also the mass of skin, internal organs, tendons, and other components. This limitation applies to a far lesser extent to the appendicular lean mass index (LMIapp).Objectives: The aim of the study was to evaluate skeletal muscle mass in children with CP using total lean BMI (LMItot) and LMIapp.Methods: The present study was a monocentric retrospective analysis of prospectively collected data among children and adolescents with CP participating in a rehabilitation program. In total, 329 children with CP [148 females; Gross Motor Function Classification Scale (GMFCS) I, 32 children; GMFCS II, 73 children; GMFCS III, 133 children; GMFCS IV, 78 children; and GMFCS V, 13 children] were eligible for analysis. The mean age was 12.3 +/- 2.75 y. Pediatric reference centiles for age-adjusted LMIapp were generated using data from NHANES 1999-2004. Low skeletal muscle mass was defined as a z score for DXA determined LMItot and LMIapp less than or equal to-2.0.Results: The z scores for LMIapp were significantly lower than LMItot in children with CP, GMFCS levels II-V (P Conclusions: The prevalence of low skeletal muscle mass in children with CP might be underestimated by LMItot. LMIapp is more suitable for the evaluation of skeletal muscle mass in children with CP.

Background Waist circumference (WC) and z scores of body mass index (BMI) are commonly used to predict childhood obesity, although BMI and WC have a limited sensitivity. Objectives To generate an artificial neural network (ANN), using the input parameters age, height, weight, and WC, to predict excess body fat in children. Methods As part of the National Health and Nutrition Examination Survey (NHANES) study, in the years 1999 to 2004, the body fat percentage of randomly selected Americans from 8 to 19 years were measured using whole-body dual energy X-ray absorptiometry (DXA) scans. Excess body fat was defined as a body fat percentage >= 85th centile. Results The data of 1999 children (856 female) were eligible. In females, the sensitivity of the BMI, WC, and ANN approaches to predict excess body fat were 0.751 (95% CI, 0.730-0.771), 0.523 (0.487-0.559), and 0.782 (0.754-0.810), respectively. In males, the sensitivity of the BMI, WC, and ANN approaches to predict excess body fat were 0.721 (95% CI, 0.699-0.743), 0.572 (0.549-0.594), and 0.795 (0.768-0.821). Conclusions Only in boys, the diagnostic performance in identifying excess body fat was better by using an ANN than by applying BMI and WC z scores. In girls, the ANN and BMI z scores performed comparable and significantly better than WC z scores.

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous connective tissue disorder characterized by bone fragility and skeletal deformity. To maintain skeletal strength and integrity, bone undergoes constant remodeling of its extracellular matrix (ECM) tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. There are at least 20 recognized OI-forms caused by mutations in the two collagen type I-encoding genes or genes implicated in collagen folding, posttranslational modifications or secretion of collagen, osteoblast differentiation and function, or bone mineralization. The underlying disease mechanisms of non-classical forms of OI that are not caused by collagen type I mutations are not yet completely understood, but an altered ECM structure as well as disturbed intracellular homeostasis seem to be the main defects. The ECM orchestrates local cell behavior in part by regulating bioavailability of signaling molecules through sequestration, release and activation during the constant bone remodeling process. Here, we provide an overview of signaling pathways that are associated with known OI-causing genes and discuss the impact of these genes on signal transduction. These pathways include WNT-, RANK/RANKL-, TGFβ-, MAPK- and integrin-mediated signaling as well as the unfolded protein response.

Lumbar spine bone mineral density (LS-BMD) assessed by dual-energy X-ray absorptiometry (DXA) is used in children to evaluate bone health. LS-BMD results in children are influenced significantly by height and BMI. An adjustment for these parameters may improve the clinical use of the method. DXA evaluation is considered useful in children to assess bone health. For this purpose, lumbar spine bone mineral density (LS-BMD) and bone mineral apparent density (LS-BMAD) are often used. The aim of the study was to estimate the effect of height and BMI on LS-BMD and LS-BMAD in children and adolescents and to develop a method to adjust individual results for these factors. As part of the National Health and Nutrition Examination Survey (NHANES) study, between the years 2005 and 2010 lumbar DXA scans on randomly selected Americans from 8 to 20 years of age were carried out. From all eligible DXA scans, three major US ethnic groups were evaluated (Non-Hispanic Whites, Non-Hispanic Blacks, and Mexican Americans) for further statistical analysis. The relationship between height as well as BMI for age Z-scores and age-adjusted LS-BMD and LS-BMAD Z-scores was analyzed. For the statistical analysis, the DXA scans of 1799 non-Hispanic White children (823 females), of 1696 non-Hispanic Black children (817 females), and of 1839 Mexican American children (884 females) were eligible. The statistical analysis showed that taller and heavier children had significantly (p

Spatial learning and associating spatial information with individual experience are crucial for rodents and higher mammals. Hence, studying the cellular and molecular cascades involved in the key mechanism of information storage in the brain, synaptic plasticity, has led to enormous knowledge in this field. A major open question applies to the interdependence between synaptic plasticity and its behavioral correlates. In this context, it has become clear that behavioral aspects may impact subsequent synaptic plasticity, a phenomenon termed behavioral metaplasticity. Here, we trained control and pilocarpine-treated chronically epileptic rats of two different age groups (adolescent and adult) in a spatial memory task and subsequently tested long-term potentiation (LTP) in vitro at Schaffer collateral—CA1 synapses. As expected, memory acquisition in the behavioral task was significantly impaired both in pilocarpine-treated animals and in adult controls. Accordingly, these groups, without being tested in the behavioral training task, showed reduced CA1-LTP levels compared to untrained young controls. Spatial memory training significantly reduced subsequent CA1-LTP in vitro in the adolescent control group yet enhanced CA1-LTP in the adult pilocarpine-treated group. Such training in the adolescent pilocarpine-treated and adult control groups resulted in intermediate changes. Our study demonstrates age-dependent functional metaplasticity following a spatial memory training task and its reversal under pathological conditions.