Adolescent Bone Research Articles

Surgical management of adolescent both bone forearm fractures using a plate and screws versus an intramedullary elastic nail

Surgical management of adolescent both bone forearm fractures using a plate and screws versus an intramedullary elastic nail

Application of CT Medical Imaging Technology in the Diagnosis of the Impact of Exercise on the Development of Adolescent Metacarpal Bone

Objective: Based on the principles of sports biomechanics, this paper uses CT medical imaging technology to observe the effect of volleyball on the morphology and structure of the metacarpal bone. Methods: Nine young professional volleyball players (volleyball group) and 8 non-volleyball players (control group) were selected from our province. They were male and right-handed. Scan the subject's hand with multi-layer spiral CT, and perform 2D and 3D reconstruction on it. The 2D reconstructed image is filtered, grayed, enlarged, intercepted, enhanced, and segmented to measure the gray value of each metacarpal bone. After manual segmentation of the 3D reconstructed image in the workstation, the CT value, length, volume, and width of each side of the metacarpal head were measured, and the size and index of each metacarpal head were calculated. Statistical analysis of differences in metacarpal parameter values. Results: Compared with the control group, (1) the volleyball group reduced the gray value of the right hand I, V metacarpal and left hand I to V metacarpal bones (P < 0.05), and the right hand II metacarpal bone decreased. (P < 0.001), the gray value of the third and fourth metacarpal bones of the right hand decreased (P < 0.01); Conclusion : The stress caused by volleyball can adaptively change the morphology and structure of the metacarpal bones of young athletes, as follows: Values, CT values decreased; metacarpal length, volume, and metacarpal head size (volume) increased; metacarpal head index decreased; in addition, non-snooker palm bone morphology and structure changed similarly to the spiker.

Effect of HIV Infection on Growth and Bone Density in Peripubertal Children in the Era of Antiretroviral Therapy: A Cross-Sectional Study in Zimbabwe

Background: Poor linear growth and pubertal delay, both common in children with HIV (CWH) in sub-Saharan Africa, may affect adolescent bone accrual and future fragility fracture risk. We investigated the association of HIV with size-adjusted bone density in peri-pubertal children in Zimbabwe. Methods: CWH aged 8-16 years taking ART for ≥2 years from public-sector HIV clinics in Harare, and HIV-uninfected children from schools in the same catchment area, were recruited into a cross-sectional study. Sociodemographic, clinical and anthropometric data were collected. Outcomes were dual-energy X-ray absorptiometry (DXA) measured total-body less-head bone mineral content-for-lean mass adjusted for height (TBLH-BMCLBM) and lumbar spine bone mineral apparent density (LS-BMAD). Linear regression models using multiple imputation for missing data, assessed relationships between risk factors and DXA measures by HIV status, and interaction by sex and pubertal (Tanner) stage. Findings: We recruited 303 CWH and 306 without HIV, mean (SD) age 12.5 (2.5) years and 50% female. Mean ART duration was 7.9 (2.6) years; for 34% ART included tenofovir disproxil fumarate (TDF). The prevalence of low TBLH-BMCLBM and LS-BMAD (Z-Score<-2) was higher in children with than without HIV (10.4% vs. 6.2%, p=0.066; 14.3% vs. 5.8%, p=0.001 respectively). HIV and male sex were associated with earlier Tanner stage. The negative effects of HIV on TBLH-BMCLBM and LS-BMAD were more pronounced with pubertal maturation, particularly in females. Among CWH, years of TDF exposure and orphanhood were strongly associated with lower TBLH-BMCLBM Z-Score in both unadjusted and adjusted analyses. Current TDF use was associated with 0.40 (95%CI 0.07, 0.73; p=0.018) and 0.31 (0.07, 0.69; p=0.110) lower TBLH-BMCLBM and LS-BMAD Z-Scores respectively. Interpretation: Despite ART, HIV is associated with substantial skeletal deficits by the end of puberty. The size of bone deficits associated with TDF and its widespread use in children in sub-Saharan Africa raise concern for future adult fracture risk. Funding Statement: Wellcome Trust. Declaration of Interests: RR (206764/Z/17/Z) RAF (206316/Z/17/Z) are funded by the Wellcome Trust. CK is funded by a National Institute of Health (NIH) Fogarty Trent Fellowship. AMR is partially supported by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement which is also part of the EDCTP2 programme supported by the European Union Grant Ref: MR/R010161/1. All other authors declare no competing interests. Ethics Approval Statement: Ethical and governance approvals were granted by the London School of Hygiene and Tropical Medicine Ethics Committee (Ref: 15333), the Institutional Review Board of the Biomedical Research and Training Institute in Harare (Ref: AP145/2018), the Joint Research Ethics Committee for University of Zimbabwe College of Health Sciences and the Parirenyatwa Group of Hospitals (Ref: 11/18), Harare Central Hospital Ethics Committee (Ref: 170118/04), the Medical Research Council of Zimbabwe (Ref: MRCZ/A/2297) and the Ministry of Primary and Secondary Education Zimbabwe (Ref: C/426/Harare). Guardians provided written informed consent and children provided written assent.

Fibrocartilaginous mesenchymoma with an unusual location in the rib.

Fibrocartilaginous mesenchymoma is a rare bone tumor, with fewer than 35 cases reported in the literature since 1984. This tumor usually occurs in the long bones of children and adolescents. In the current case, the tumor affected a rib. A 17-year-old boy presented with a mass in the right fifth rib. Radiologic findings revealed an osteolytic mass with cortical destruction and calcification; en bloc resection was performed. The tumor showed three distinct histologic features: bland spindle cell proliferation, benign cartilage nodules, and epiphyseal plate-like enchondral ossification. The pathologic diagnosis was fibrocartilaginous mesenchymoma. The patient remains free of disease 1 year after the surgery. Pathological diagnosis of fibrocartilaginous mesenchymoma can be challenging, especially when the tumor occurs in an unusual site. When any fibro-osseous lesion with a cartilaginous component is encountered, the possibility of fibrocartilaginous mesenchymoma should be considered because of its locally aggressive behavior.

Bone Metabolism in Adolescents Undergoing Bariatric Surgery.

The prevalence of childhood obesity has increased over past decades with a concomitant increase in metabolic and bariatric surgery (MBS). While MBS in adults is associated with bone loss, only a few studies have examined the effect of MBS on the growing skeleton in adolescents. This mini-review summarizes available data on the effects of the most commonly performed MBS (sleeve gastrectomy and gastric bypass) on bone in adolescents. A literature review was performed using PubMed for English-language articles. Dual-energy x-ray absorptiometry (DXA) measures of areal bone mineral density (aBMD) and BMD Z scores decreased following all MBS. Volumetric BMD (vBMD) by quantitative computed tomography (QCT) decreased at the lumbar spine while cortical vBMD of the distal radius and tibia increased over a year following sleeve gastrectomy (total vBMD did not change). Reductions in narrow neck and intertrochanteric cross-sectional area and cortical thickness were observed over this duration, and hip strength estimates were deleteriously impacted. Marrow adipose tissue (MAT) of the lumbar spine increased while MAT of the peripheral skeleton decreased a year following sleeve gastrectomy. The amount of weight loss and reductions in lean and fat mass correlated with bone loss at all sites, and with changes in bone microarchitecture at peripheral sites. MBS in adolescents is associated with aBMD reductions, and increases in MAT of the axial skeleton, while sleeve gastrectomy is associated with an increase in cortical vBMD and decrease in MAT of the peripheral skeleton. No reductions have been reported in peripheral strength estimates.

Karachi Cancer Registry (KCR): Age-Standardized Incidence Rate by Age-Group and Gender in a Mega City of Pakistan.

Objectives:To estimate the cancer incidence by age group and gender for the population of Karachi Division by analyzing the Karachi Cancer Registry data of 2017-19. Settings:The population of Karachi division is 16.1 million according to national census 2017. ‘Karachi Cancer Registry’ which is a part of ‘National Cancer Registry’ is collecting data from eight major hospitals in Karachi since 2017. For outcome measures, cancer counts and the age standardized incidence rates (ASIR) per 100,000 population were computed for age groups (0–14, 15–19 and ≥20 years), in both genders and all cancer site/type. Methods:The population denominators were based on the population of Karachi division estimated at 16.1 million in the population census, 2017. Counts and age-standardized incidence rates (ASIR) were calculated for each of the three age categories. Results:From Jan 2017 till Dec 2019 a total of 33,309 malignant cases were recorded in KCR database comprising 17,490 (52.5%) females and 15,819 (47.5%) males. ASIRs in age groups 0-14, 15-19 and ≥ 20 years, among female were 11.5, 2.4 and 223.6 and in males were 17.6, 3.2 and 216.7 respectively. The commonest diagnosis in children, adolescent and adults were (1) among females: children; bone (3.12), leukemia (2.09) brain/CNS (1.26); in adolescents: bone (0.78), brain/CNS (0.27), connective and soft tissue (0.11), in adults: breast cancer (76.07), oral cancer (16.68) and ovary (10.89) respectively, and (2) among males: children; bone (4.56), leukemia (2.79) and brain/CNS (1.88); in adolescent; bone (1.19), brain/CNS (0.31) and leukemia (0.21) and in adults: oral cancer (42.83), liver (16.10) and bone (13.37) respectively. Conclusion:Oral Cancer, a largely preventable cancer is the leading cancer in Karachi adult males while in female adults Breast Cancer is the leading cancer followed by Oral Cancer. In children and adolescents Bone, Leukemia and Brain/CNS malignancies are most common.

Gestational perfluoroalkyl substance exposures and early adolescent bone mineral density in the HOME Study

Background/Aim: Perfluoroalkyl substances (PFAS) may impair bone health via endocrine disruption and nuclear hormone receptor activation. Bone mineral accrual during adolescence is important for long-term bone health, but human studies of PFAS and bone mineral density are primarily in adults or use a cross-sectional study design. We estimated associations of gestational PFAS exposures with early adolescent areal bone mineral density (aBMD) in a prospective cohort study. Methods: We examined 225 pregnant mothers enrolled from 2003-2006 in Cincinnati, OH and their children in the HOME Study. We measured concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononaoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) in maternal serum collected at 16 weeks gestation. When children were 12 years old, we measured lean body mass and total body, spine, total hip, femoral neck, and distal forearm (1/3 radius) aBMD with dual x-ray absorptiometry and calculated height-, age-, sex-, and race-specific aBMD z-scores. Using linear regression, we estimated covariate-adjusted associations in aBMD z-scores per doubling of gestational PFAS concentrations overall and stratified by sex. We estimated the proportion of total effects that were mediated by lean mass using structural equation modeling. Results: In adjusted models, higher PFOA concentrations were associated with lower aBMD z-scores of the forearm (β: -0.28, 95% CI: -0.49, -0.08), total hip (β: -0.28, 95% CI: -0.54, -0.02), and spine (β: -0.34, 95% CI: -0.61, -0.06) in males but not females. Lean mass mediated 29-50% of these associations. Higher PFHxS and PFNA concentrations were associated with lower aBMD z-scores of the forearm (PFHxS β: -0.11, 95% CI: -0.23, 0.00; PFNA β: -0.14, 95% CI: -0.35, 0.06), with no modification by sex or mediation by lean mass. PFOS was not associated with aBMD measures in either sex. Conclusions: Gestational PFAS exposures may reduce bone accrual in early adolescence, possibly in a sex-dependent manner.

Knockdown of STIP1 inhibits the invasion of CD133‑positive cancer stem‑like cells of the osteosarcoma MG63cellline via the PI3K/Akt and ERK1/2 pathways.

Osteosarcoma is the most common primary malignant tumor of the bone in adolescents and children, with high rates of metastasis and a poor prognosis. Recently, osteosarcoma cancer stem/stem‑like cells(CSCs) have been identified as the main cause of recurrence and metastasis. Stress‑induced phosphoprotein1 (STIP1), a co‑chaperone that binds to heat shock proteins70 and90, is abnormally expressed in several tumor cell lines, and may play an important role in tumor cell migration and invasion. These features indicate that STIP1 may represent a new therapeutic target for osteosarcoma CSCs. However, the role of STIP1 in osteosarcoma CSC migration and invasion remains largely unknown. In the present study, CD133‑positive osteosarcoma CSCs were first isolated and cultured by magnetic cell sorting and serum‑free medium suspension cell sphere culture, respectively. Knockdown of STIP1 by small interfering RNA significantly was then shown to inhibit the migration and invasion of these cells, possibly due to the regulation of the expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and tissue inhibitor of metalloproteinase‑2. Furthermore, data from the present study suggested that the knockdown of STIP1 decreased the levels of phosphorylated Akt and phosphorylated ERK1/2. In summary, these findings indicate that targeting STIP1 in osteosarcoma may constitute a viable molecular targeted therapy strategy for the inhibition of CSC invasion and migration.

Finite element analysis for prediction of adolescent bone strength: micro vs continuum models

Adolescence is a crucial period for bone growth, and many factors during this period can influence bone quality and the intensity of peak bone mass, e.g., nutritional intakes and physical activity ...

Clinical guidelines for burosumab in the treatment of XLH in children and adolescents: British paediatric and adolescent bone group recommendations.

X-linked hypophosphataemia (XLH) is caused by a pathogenic variant in the PHEX gene, which leads to elevated circulating FGF23. High FGF23 causes hypophosphataemia, reduced active vitamin D concentration and clinically manifests as rickets in children and osteomalacia in children and adults. Conventional therapy for XLH includes oral phosphate and active vitamin D analogues but does not specifically treat the underlying pathophysiology of elevated FGF23-induced hypophosphataemia. In addition, adherence to conventional therapy is limited by frequent daily dosing and side effects such as gastrointestinal symptoms, secondary hyperparathyroidism and nephrocalcinosis. Burosumab, a recombinant human IgG1 MAB that binds to and inhibits the activity of FGF23, is administered subcutaneously every 2 weeks. In clinical trials (phase 2 and 3) burosumab was shown to improve phosphate homeostasis that consequently resolves the skeletal/non-skeletal manifestations of XLH. Burosumab was licensed in Europe (February 2018) with the National Institute for Health and Care Excellence, UK approving use within its marketing authorisation in October 2018. In this publication, the British Paediatric and Adolescent Bone Group (BPABG) reviewed current evidence and provide expert recommendations for care pathway and management of XLH with burosumab.

Increased prevalence of fractures in inadequately transfused and chelated Indian children and young adults with beta thalassemia major.

In patients with beta thalassemia major, inadequate transfusion and chelation may compromise bone health and increase risk of fractures. The objective of this study was to describe the prevalence of fractures in Indian inadequately transfused and chelated children, adolescents and young adults with beta thalassemia major. We studied 179 patients with beta thalassemia (3.6-28.3years; 105 boys). Medical, transfusion, chelation and fracture history were recorded. Vertebral fracture assessment (VFA) was performed using lateral spine images acquired using the GE Lunar iDXA (Wisconsin, MD). Fractures were classified according to an adapted semi-quantitative method. History of non-traumatic long bone fractures was observed in 21% patients (n=37); there were significantly greater (p<0.05) number of males (n=30) than females (n=15). The 21% fracture prevalence in the present study is higher than the reported fractures of 9% in healthy Indian children and adolescents. The prevalence of vertebral fractures was 4.5% (n=8) in the study group. Of those with fractures, four patients had both long bone and vertebral fractures, and (any, long bone or vertebral fractures) sixteen patients had more than 1 fracture; eleven patients had 2 fractures, four patients had 3 fractures and one patient had 5 fractures. Thus, in 179 patients, there were a total of 68 single fractures which translates to 307 fractures per 10,000 patient years. This study found increased prevalence of non-traumatic long bone and vertebral fractures in children and adolescents with thalassemia major.

The effects of adolescent laparoscopic adjustable gastric band and sleeve gastrectomy on markers of bone health and bone turnover.

25-hydroxy vitamin D (25 OHD) deficiency and secondary hyperparathyroidism have been seen after metabolic and bariatric surgery, but data are lacking on the bone health outcomes of adolescent sleeve gastrectomy (SG). The purpose of this study was to examine bone-related nutrition after SG, compared to laparoscopic adjustable gastric band (LAGB), and trend bone turnover markers following SG. This is an observational study of 197 adolescents who underwent LAGB (n = 98) or SG (n = 99). Bone health labs were collected at baseline and 6 and/or 12 months after LAGB or SG, with additional analysis of bone turnover markers in the SG group. Calcium and 25 OHD levels increased at 6 and 12 months after LAGB and SG, with no difference between the surgeries. Parathyroid hormone levels decreased only in the SG group. SG patients had increased osteocalcin and carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) at 6 and 12 months post-SG, although CTX decreased between 6 and 12 months. Excess weight loss at 6 months predicted the rise in CTX, but the changes in osteocalcin and CTX could not be attributed to 25 OHD deficiency, hypocalcemia or hyperparathyroidism. Patients had improved 25 OHD levels post-surgery, which may be secondary to stringent vitamin supplementation guidelines. However, there were marked increases in bone turnover markers following SG. More studies are needed to evaluate the effects of SG on adolescent bone health and to correlate the early changes in bone turnover with bone mineral density and fracture risk.

FIBROUS CORTICAL DEFECT OF THE MANDIBLE: A CASE REPORT AND IMUNOHISTOCHEMICAL ANALYSIS

Fibrous cortical defect (FCD) is a benign non-neoplastic lesion, commonly found in long bones of adolescents. FCD in the jaws is rare. Only 9 cases have been previously reported, all affecting the mandible, preferentially of young females. A 15-year-old female patient was referred with complaint of swelling in the right side of the mandible. Imaginologic examination presented heterogeneous density with spiculate contour and irregularity in the basal mandibular cortex, suggesting FCD or benign fibro-osseous lesion. After surgical removal, microscopy showed a benign spindle cell proliferation with focal storiform pattern. Immunohistochemical analysis showed positivity for HLA-DR, CD68, CD163, FXIIIA, and alpha-SMA; Ki-67 labeling index

Abstract 301: RUNX3 upregulates c-MYC via mR1 – an essential genomic element for p53-deficient osteosarcomagenesis

Abstract Osteosarcoma (OS) is the most common malignancy of bone in children and adolescents. The 5-year survival rate of patients with relapse or metastasis remain 20%, underscoring a need for new treatment strategies. The disease is generally characterized by recurrent somatic alterations of p53. An osteoblast-specific p53-knockout mouse line (Sp7-Cre;p53F/F; ‘OS mouse' herein) has a high incidence of osteosarcoma with a close histopathological resemblance to that of human. Thus, the OS mouse serves as a rational animal model to study molecular mechanisms of OS development. RUNX3/Runx3 was proved oncogenic in osteosarcomagenesis. We found dominant upregulation of RUNX3 in both human and mouse OS tissues, analyzing gene expression profiles of human OS cases, most of which possess genetically inactivated p53, and those of OS mice. Both human OS cell lines and mouse OS cells cloned from OS mice showed a strong dependency on RUNX3 for tumorigenicity in nude mice. Heterozygous deletion of Runx3 efficiently extended lifespans of OS mice. c-MYC/c-Myc was identified as a positive target of RUNX3. Combining microarray and ChIP-seq analyses of mouse OS cells, we found that c-Myc is transcriptionally upregulated by Runx3. In human and mouse OS cells, expression levels of RUNX3 and c-MYC correlated well with each other and knockdown of RUNX3 greatly reduced c-MYC expression and tumorigenicity. Heterozygous deletion of c-Myc, as well as that of Runx3, prevented osteosarcomagenesis of OS mice. In OS patients, mRNA levels of RUNX3 and c-MYC showed a positive correlation and high expression of each was a predictor of poor prognosis. Furthermore, we located a requisite genomic element for c-MYC induction by RUNX3. Assessing the ChIP-seq profiles of mouse OS cells, we selected several candidates of genomic elements responsible for upregulation of c-Myc within its 3-megabase topological association domain. Epigenome/genome editing of these candidates in human and mouse OS cells revealed that a genomic element ‘mR1', the 6-bp RUNX consensus binding site most proximal to the c-MYC/c-Myc promoter, is essential for c-MYC induction by RUNX3 and tumorigenicity. Indeed, homozygous disruption of mR1 effectively suppressed osteosarcomagenesis of OS mice and thus improved their survivals. Taken together, we propose RUNX3 as a central oncogenic figure in p53-deficient osteosarcomagenesis: RUNX3 is somehow upregulated upon inactivation of p53 and then starts to aberrantly upregulate c-MYC. Moreover, we propose mR1 as an essential genomic element for overexpression of c-MYC by RUNX3. Importantly, mR1-null mice are viable and fertile whereas c-Myc-null mice result in embryonic lethality. This indicates that mR1 is required not for physiological expression of c-MYC in normal development, but for its aberrant upregulation by RUNX3 in osteosarcomagenesis, providing a rationale for targeting mR1 as a novel therapy of OS. Citation Format: Yuki Date, Shohei Otani, Tomoya Ueno, Kosei Ito. RUNX3 upregulates c-MYC via mR1 – an essential genomic element for p53-deficient osteosarcomagenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 301.

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma.

Osteosarcoma (OS, also known as osteogenic sarcoma) is the most common primary malignancy of bone in children and adolescents. The molecular mechanisms of OS are extremely complicated and its molecular mediators remain to be elucidated. We sequenced total RNA from 18 OS bone samples (paired normal-tumor biopsies). We found statistically significant (FDR <0.05) 26 differentially expressed transcript variants of LEPROT gene with different expressions in normal and tumor samples. These findings contribute to the understanding of molecular mechanisms of OS development and provide encouragement to pursue further research.

Chondrosarcoma of bone in children and adolescents

PurposeChondrosarcomas typically present in adults during the fifth to seventh decades and are rare in young patients. The biological behaviour and oncological outcomes may be different in children and adolescents.MethodsWe retrospectively evaluated the outcomes of all patients with chondrosarcoma of bone who were younger than 18 years of age at the time of diagnosis and were treated at our centre between 1995 and 2018.ResultsThe 15 consecutive patients studied included nine male and six female cases, with a mean age at diagnosis of 13 years (7 to 17). The median follow-up was 117 months (30 to 277). The tumours were primary and secondary in ten and five patients, respectively. The tumours were central in 13 and surface in two patients. The tumour locations were the humerus in five, digits in five, femur in three, radius in one and pelvis in one patient. The histological grades were grade I in seven, grade II in seven and grade III in one patient. The surgical treatments were limb salvage in ten patients and ray amputation in five patients. The surgical margins were wide in eight, marginal in two and intralesional in five patients. All the patients were alive and continuously free of disease at the time of the last follow-up. No patient developed metastases or local recurrence.ConclusionChondrosarcoma of bone in children and adolescent patients has a very good prognosis and is less aggressive compared with published outcomes in older patients.Level of evidenceIV

Categorizing 10 Sports According to Bone and Soft Tissue Profiles in Adolescents.

Considering the different loading and training characteristics of the sports practiced during growth, it is important to specify and categorize the bone and soft tissue adaptations in adolescent athletes. This study aimed to categorize 10 different loading sports and a nonsport group and identify the differences in bone density and soft tissues. The sample included 625 adolescents (10 to 17 yr of age) of 10 sports (soccer, basketball, volleyball, track and field, judo, karate, kung fu, gymnastics, baseball, and swimming) and a nonsport group. Dual-energy x-ray absorptiometry assessed areal bone mineral density (aBMD), bone mineral apparent density (BMAD), and soft tissues (lean soft tissue and fat mass). The results were adjusted for sex, peak height velocity status, lean soft tissue, fat mass, and weekly training volume. The comparisons among groups showed that soccer had the highest whole-body aBMD (mean ± SEM: 1.082 ± 0.007 g·cm) and lower limb aBMD (1.302 ± 0.010 g·cm). Gymnastics presented the highest upper limb aBMD (0.868 ± 0.012 g·cm) and whole-body BMAD (0.094 ± 0.001 g·cm). Swimming presented the lowest aBMD values in all skeletal sites (except at the upper limbs) and whole-body BMAD. The soft tissue comparisons showed that soccer players had the highest lean soft tissue (43.8 ± 0.7 kg). The lowest fat mass was found in gymnasts (8.04 ± 1.0 kg). The present study investigated and categorized for the first time 10 different sports according to bone density and soft tissue profiles. Soccer and gymnastics sport groups were found to have the highest bone density in most body segments, and both sports were among the groups with the lowest fat mass.

Abstract B28: A cross-species enhancer activity analysis approach to identify the Ewing sarcoma cell of origin

Abstract Ewing sarcoma is a malignant bone and soft tissue tumor in children and adolescents. In 85% of all cases the formation of Ewing sarcoma is caused by a chromosomal translocation, leading to the expression of the oncogene EWS-FLI1. This aberrant transcription factor is the main driver of the disease and leads to massive transcriptional dysregulation. Although the genetic mechanism driving Ewing sarcoma is well understood, an animal model adequately mimicking the disease is still lacking. One reason why modeling attempts have remained difficult is the elusive cell of origin in Ewing sarcoma. Several cell types including neural crest progenitor cells and mesenchymal stem cells have been proposed, but none of them has yet been confirmed as cell of origin of Ewing sarcoma. Towards identifying this cell of origin, we are currently following a novel cross-species approach by exploring the use of enhancers, which are specifically active in Ewing sarcoma cells, but were not created de novo by EWS-FLI1. Injection of reporter constructs into zebrafish embryos allows for visualization of cell types with activity of the selected enhancers and provides us with cell-of-origin candidate cell types. To investigate which of these candidate cells are permissive for development of Ewing-like tumors, we will also express EWS-FLI1 in these cells. If successful, this approach will not only reveal the Ewing sarcoma cell of origin but also result in a zebrafish Ewing sarcoma model, which will help to understand tumor initiation and progression and, furthermore, will be a valuable tool to develop novel therapeutic strategies. Citation Format: Sarah Grissenberger, Anna Poetsch, Monika Heinzl, Luisa Morelli, Nathan Sheffield, Niko Popitsch, Heinrich Kovar, Martin Distel. A cross-species enhancer activity analysis approach to identify the Ewing sarcoma cell of origin [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B28.

Shedding "LIGHT" on the Link between Bone and Fat in Obese Children and Adolescents.

Obesity may affect bone health, but literature reports are contradictory about the correlation of body mass index (BMI) and bone markers. LIGHT, one of the immunostimulatory cytokines regulating the homeostasis of bone and adipose tissue, could be involved in obesity. The study involved 111 obese subjects (12.21 ± 3.71 years) and 45 controls. Patients underwent the evaluation of bone status by quantitative ultrasonography (QUS). LIGHT amounts were evaluated in sera by ELISA, whereas its expression on peripheral blood cells was evaluated by flow cytometry. Osteoclastogenesis was performed by culturing peripheral blood mononuclear cells (PBMCs) with or without anti-LIGHT antibodies. Obese patients showed significant high BMI-standard deviation score (SDS), weight-SDS, and Homeostatic model assessment for insulin resistance (HOMA-IR) that negatively correlated with the reduced Amplitude Dependent Speed of Sound (AD-SoS)-Z-score and Bone Transmission Time (BTT-Z)-score. They displayed significantly higher serum levels of LIGHT compared with controls (497.30 ± 363.45 pg/mL vs. 186.06 ± 101.41 pg/mL, p < 0.001). LIGHT expression on monocytes, CD3+-T-cells, and neutrophils was also higher in obese patients than in the controls. Finally, in PBMC cultures, the addition of anti-LIGHT antibodies induced a significant osteoclastogenesis inhibition. Our study highlighted the high serum levels of LIGHT in obese children and adolescents, and its relationship with both the grade of obesity and bone impairment.

Participation In Sports During Adolescence Positively Impacts Bone Health In Recruits Entering Basic Combat Training

It is well documented that participation in sports during childhood is beneficial to skeletal health. Almost 40% of bone mineral content is attained during years of peak height velocity (females 10-14y; males 12-16y). Improving bone development during these years may be beneficial in mitigating musculoskeletal injuries (MSKIs) in Soldiers. PURPOSE: To evaluate the relationship between participation in sports during adolescence and baseline bone microarchitectural parameters in recruits entering Basic Combat Training (BCT). METHODS: Survey data on sport participation from 840 Army recruits entering BCT were analyzed (611M, 25.0±3.7 kg/m2, 20.6±3.6y; 229F, 23.6±2.7 kg/m2, 20.4±3.5y). Low impact (LI) and high impact (HI) sports were categorized according to effective load stimulus scores. Middle school (MS) was defined as grades 6-8 (11-14y) and high school (HS) as grades 9-12 (14-18y). Baseline bone characteristics were measured at the ultradistal tibia using a high resolution CT scanner. Linear models were used to evaluate the association between bone microarchitecture and timing and impact category of sport played. Models were adjusted for ethnicity, BMI, age, and parents’ education. Effect estimates (EE) and p values for bone parameters compared to recruits who did not play sports (98M, 46F) are presented. RESULTS: Table 1 shows that participation in both low and high impact sports during adolescence had a significant effect on baseline bone measures in male and female recruits compared to those who did not participate in sports. While male sports participation in HS had a greater effect than MS sports participation, the opposite was observed in females. We found no significant effects in trabecular thickness, spacing or number. CONCLUSION: Promoting sports participation in children and adolescents, particularly during peak growth years, is important in providing long term skeletal health benefits and may help to reduce MSKIs in Soldiers.