Skeletal Health and Bone Marrow Composition Among Youth

青少年骨骼健康和骨髓成分

• 批准号: 10401768
• 负责人: CATHERINE M. GORDON
• 金额: $ 58.29万
• 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/10401768
• 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 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; Female; 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; Research; Research Personnel; Sex Characteristics; Site; Skeleton; Spectrum Analysis; Structure; Testosterone; Time; Translating; Well in self; Work; X-Ray Computed Tomography; Yellow Marrow; Youth; bone; bone health; bone mass; clinically relevant; clinically significant; cohort; critical period; experience; fracture risk; gender dysphoria; health related quality of life; hormone therapy; insight; male; patient population; physical conditioning; recruit; restrictive eating; sex; skeletal; spectroscopic imaging; 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.

摘要 患有性别焦虑症的变性青年通常使用促性腺激素释放激素(GnRH)进行治疗 抑制性激素和青春期发育的激动剂。然而，在ITS上提供的信息很少 青春期变性人青年对骨骼健康的影响。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，妥协 青少年和成人的成骨、骨形成和骨密度。目前的调查人员已经 先前证明，患有限制性饮食障碍和雌激素减退的青少年经历 随着疾病的发展，骨髓从红(造血系)骨髓向黄(脂肪)骨髓转变。这些骨头 骨髓的变化可能对骨形成、骨吸收有不利的长期影响 青春期，最终是终生的骨骼健康。检查骨髓成分是如何改变的 变性人青年的青春期障碍及其与骨密度、结构和横断面的关系 几何学，可以提供对促性腺激素释放激素激动剂对年轻、未成熟的 骷髅。这项提案将研究青春期封锁对骨骼的影响，青春期封锁是变性人的初始阶段 医疗管理，在性别确认荷尔蒙治疗(雌激素或睾酮治疗)之前。这个 这项研究将为跨性别青年的骨骼健康提供新的见解，通过 磁共振成像(MRI)和波谱(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)和 研究工具，外周定量计算机断层扫描(PQCT)。我们还将解决临床上的 年轻人骨髓成分与骨密度和骨强度关系的相关问题 正在经历青春期封锁的青少年。我们将招募一批青少年，包括那些 出生时指定的女性(AFAB)和出生时指定的男性(AMAB)，并匹配健康对照组，以及 检查骨髓成分(通过MRI/MRS)、骨密度(通过DXA+pQCT)和骨结构 青春期阻断12个月前后的横断面几何(PQCT)。这个项目将 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 具有丰富的DXA、pQCT和MRI/MRS经验。在探索性目标中，我们还将考虑 青春期阻碍焦虑、抑郁和与健康相关的生活质量。拟议研究的结果 将使我们能够确定预防策略，以对抗青春期潜在的长期不良后遗症 封锁早期骨质疏松症和骨折，提高对跨性别青年提供者的认识，以及 帮助指导收到促性腺激素释放激素激动剂后的监测。