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 患有性别不安的跨性别青少年通常接受促性腺激素释放激素 (GnRH) 治疗 抑制性类固醇和青春期发育的激动剂。然而，关于其的信息却很少 对青春期前后跨性别青少年骨骼健康的影响。性类固醇抑制可以改变 间充质干细胞优先分化为脂肪细胞而不是成骨细胞，从而损害 青少年和成人的成骨、骨形成和骨密度。目前调查人员已 先前证明，患有限制性饮食失调和雌激素低下症的青少年会经历 随着疾病的进展，骨髓从红色（造血）骨髓转变为黄色（脂肪）骨髓。这些骨头 骨髓变化可能对骨形成、骨增生产生长期不利影响 青春期，并最终影响终生骨骼健康。检查骨髓成分在术后如何改变 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 几何学，可以提供 GnRH 激动剂对年轻、不成熟的人的影响的机制理解 骨骼。该提案将研究青春期封锁（跨性别的初始阶段）对骨骼的影响 在性别确认激素治疗（雌激素或睾酮治疗）之前进行医疗管理。这 研究将为跨性别青少年的骨骼健康提供新的见解，通过检查骨髓成分 磁共振成像（MRI）和光谱学（MRS）。这些结果将与 BMD 相关 通过临床评估工具、双能 X 射线吸收测定法 (DXA) 和 研究工具，外周定量计算机断层扫描（pQCT）。我们还将讨论临床 年轻人的骨髓成分如何与骨密度和骨骼强度相关的相关问题 正经历青春期封锁的青少年。我们将招募一批青少年，包括 指定出生时女性 (AFAB) 和指定出生时男性 (AMAB)，以及匹配的健康对照，以及 检查骨髓成分（通过 MRI/MRS）、骨密度（通过 DXA + pQCT）和骨结构 青春期封锁 12 个月之前和之后的横截面几何形状（通过 pQCT）。该项目将 利用我们庞大的患者群体在国家认可的儿科医院和我们的医院进行两地研究 在 DXA、pQCT 和 MRI/MRS 方面拥有丰富的经验。在探索性目标中，我们还将考虑以下效果： 青春期对焦虑、抑郁和健康相关生活质量的封锁。拟议研究的结果 将使我们能够确定预防策略，以应对青春期潜在的长期不良后遗症 早期骨质疏松症和骨折等封锁，提高跨性别青年提供者的认识，以及 帮助指导收到 GnRH 激动剂后的监测。