Skeletal Health and Bone Marrow Composition Among Youth

青少年骨骼健康和骨髓成分

• 批准号: 10611431
• 负责人: AMY D DIVASTA
• 金额: $ 56.87万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-06 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611431
• 关键词: Address; Adipocytes; Adolescence; Adolescent; Adult; Adverse effects; Affect; Age; Agonist; Anxiety; Awareness; Beck depression inventory; Birth; Body mass index; Bone Density; Bone Marrow; Bone Marrow Examination; Bone structure; Child; Child Health; Clinical Assessment Tool; Data; Development; Disease Progression; Distress; Dual-Energy X-Ray Absorptiometry; Eating Disorders; Equipment and supply inventories; Estrogens; Ethnic Origin; Fatty acid glycerol esters; Feeling; Fracture; Gender; Geometry; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Health; Hematopoietic; Hormonal; Hormones; Intervention; Lipids; Long-Term Effects; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Marrow; Measurement; Measures; Medical; Mental Depression; Mental Health; Mesenchymal Stem Cells; Monitor; Obesity; Osteoblasts; Osteogenesis; Osteoporosis; Outcome; Participant; Patient Self-Report; Pediatric Hospitals; Peripheral; Phase; Prevention strategy; Professional Organizations; Provider; Puberty; Questionnaires; Race; Recommendation; Research; Research Personnel; Sex Characteristics; Site; Skeleton; Spectrum Analysis; Structure; Testosterone; Time; Translating; Well in self; Work; X-Ray Computed Tomography; Yellow Marrow; Youth; assigned female at birth; assigned male at birth; bone; bone health; bone mass; clinically relevant; clinically significant; cohort; critical period; experience; fracture risk; gender affirmation; gender dysphoria; health related quality of life; hormone therapy; improved; insight; patient population; physical conditioning; puberty blocker; recruit; restrictive eating; sex; skeletal; tool; trait; transgender

ABSTRACT Transgender youth with gender dysphoria are often treated with a gonadotropin-releasing hormone (GnRH) agonist to suppress sex steroids and pubertal development. However, there is little information available on its effects on bone health in young peri-pubertal transgender youth. Sex steroid suppression can alter mesenchymal stem cells to differentiate preferentially into adipocytes over osteoblasts, compromising osteogenesis, bone formation, and bone density in both adolescents and adults. The current investigators have previously demonstrated that adolescents with restrictive eating disorders and hypoestrogenism experience bone marrow shifts from red (hematopoietic) to yellow (fatty) marrow with progression of disease. These bone marrow changes may have adverse long-term implications for bone formation, bone accretion during adolescence, and ultimately, lifetime skeletal health. Examining how bone marrow composition is altered after pubertal blockade in transgender youth, and its relation to bone density, structure, and cross-sectional geometry, could provide a mechanistic understanding of the effects of a GnRH agonist on a young, immature skeleton. This proposal will examine the skeletal effects of pubertal blockade, the initial phase of transgender medical management, prior to gender affirming hormonal therapy (estrogen or testosterone therapy). The study will provide new insights on bone health in transgender youth, examining bone marrow composition via magnetic resonance imaging (MRI) and spectroscopy (MRS). These results will be correlated with BMD measurements obtained by the clinical assessment tool, dual-energy x-ray absorptiometry (DXA), and the research tool, peripheral quantitative computed tomography (pQCT). We will also address the clinically relevant question of how bone marrow composition relates to bone density and skeletal strength in young adolescents who are undergoing pubertal blockade. We will recruit a cohort of adolescents including those assigned female at birth (AFAB) and assigned male at birth (AMAB), and matched healthy controls, and examine bone marrow composition (by MRI/MRS), bone density (by DXA + pQCT), and bone structure and cross-sectional geometry (by pQCT), before and after 12 months of pubertal blockade. This project will leverage our large patient population as a two-site study in nationally recognized pediatric hospitals and our extensive experience with DXA, pQCT, and MRI/MRS. In an exploratory aim, we will also consider the effect of pubertal blockade on anxiety, depression, and health-related quality of life. Findings from the proposed study will allow us to identify preventive strategies to counter potential long-term adverse sequelae of pubertal blockade such as early osteoporosis and fractures, raise awareness for providers of transgender youth, and help guide monitoring after receipt of a GnRH agonist.

抽象的 性别烦躁不安的跨性别青年通常用促性腺激素释放激素（GNRH）治疗 激动剂抑制性类固醇和青春期发育。但是，几乎没有有关其的信息 青年跨性别跨性别青年对骨骼健康的影响。性类固醇抑制会改变 间充质干细胞优先区分成骨细胞的脂肪细胞，妥协 青少年和成人的成骨，骨形成和骨密度。现任调查人员有 以前证明，具有限制性饮食失调和低雌激素经验的青少年 骨髓从红色（造血）转变为疾病进展的黄色（脂肪）骨髓。这些骨头 骨髓变化可能对骨形成，骨积聚可能具有不利的长期影响 青春期，最终是终身骨骼健康。检查骨髓组成如何改变之后 跨性别青年的青春期封锁及其与骨密度，结构和横截面的关系 几何形状可以提供对GnRH激动剂对年轻，不成熟的影响的机械理解 骨骼。该建议将检查青春期封锁的骨骼影响，跨性别者的初始阶段 医疗管理，在确认激素疗法（雌激素或睾丸激素治疗）之前。这 研究将提供有关跨性别青年骨骼健康的新见解，通过 磁共振成像（MRI）和光谱法（MRS）。这些结果将与BMD相关 通过临床评估工具，双能X射线吸收法（DXA）获得的测量值和 研究工具，外围定量计算机断层扫描（PQCT）。我们还将在临床上讲话 骨髓组成如何与年轻的骨密度和骨骼强度有关的相关问题 正在经历青春期封锁的青少年。我们将招募包括其中包括的青少年 出生时分配女性（AFAB），并在出生时分配男性（AMAB），并匹配健康的对照，并且 检查骨髓组成（通过MRI/MRS），骨密度（由DXA + PQCT）以及骨结构以及 横截面几何形状（由PQCT），在青春期封锁12个月之前和之后。这个项目将 在全国认可的儿科医院和我们的 DXA，PQCT和MRI/MRS的丰富经验。为了探索目的，我们还将考虑 焦虑，抑郁和与健康相关的生活质量的青春期封锁。拟议研究的发现 将使我们能够确定预防性策略，以应对青春期的潜在长期不良后遗症 封锁，例如早期骨质疏松和骨折，提高对跨性别青年提供者的认识，以及 收到GnRH激动剂后，帮助指导监测。