Skeletal Health and Bone Marrow Composition in Transgender Youth

跨性别青年的骨骼健康和骨髓成分

• 批准号: 10707623
• 负责人: CATHERINE M. GORDON
• 金额: $ 16万
• 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/10707623
• 关键词: Address; Adipocytes; Adolescence; Adolescent; Adult; Adverse effects; Affect; Agonist; Anxiety; Awareness; Birth; Bone Density; Bone Marrow; Bone Marrow Examination; Bone structure; Clinical Assessment Tool; Development; Disease Progression; Dual-Energy X-Ray Absorptiometry; Eating Disorders; Estrogens; Fracture; Geometry; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Health; Hematopoietic; Magnetic Resonance Imaging; Marrow; Measurement; Medical; Mental Depression; Mental Health; Mesenchymal Stem Cells; Monitor; Osteoblasts; Osteogenesis; Osteoporosis; Outcome; Pediatric Hospitals; Peripheral; Phase; Prevention strategy; Provider; Research; Research Personnel; Site; Skeleton; Spectrum Analysis; Structure; Testosterone; Well in self; Work; X-Ray Computed Tomography; Youth; assigned female at birth; assigned male at birth; bone; bone health; clinically relevant; cohort; experience; gender affirmation; gender dysphoria; health related quality of life; hormone therapy; insight; patient population; physical conditioning; puberty blocker; recruit; restrictive eating; skeletal; tool; 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，造成骨的生成，骨骼 青少年和成人的形成和骨密度。目前的调查人员以前有 证明患有限制性饮食失调和低雌激素的青少年经历了骨髓 随着疾病进展的黄色（造血）转移到黄色（脂肪）骨髓。这些骨髓变化 可能对骨形成，青春期骨积聚的长期影响不良，最终 终身骨骼健康。检查青春期封锁后如何改变骨髓成分 变性青年及其与骨密度，结构和横截面几何形状的关系，可以提供 对GnRH激动剂对年轻，未成熟骨骼的影响的机械理解。该提议将 在跨性别医疗管理的初始阶段检查青春期封锁的骨骼影响，然后 性别确认激素疗法（雌激素或睾丸激素治疗）。该研究将提供有关的新见解 跨性别青年的骨骼健康，通过磁共振成像检查骨髓组成（MRI） 和光谱法（MRS）。这些结果将与临床获得的BMD测量相关 评估工具，双能X射线吸收法（DXA）和研究工具，外围定量 计算机断层扫描（PQCT）。我们还将解决有关骨髓如何与临床相关的问题 组成涉及正在经历青春期的年轻青少年的骨骼密度和骨骼强度有关 封锁。我们将招募一群青少年，包括分配的女性（AFAB）并分配的青少年 出生时男性（AMAB），并匹配健康对照，并检查骨髓组成（MRI/MRS）， 骨密度（通过DXA + PQCT），以及骨结构和横截面几何（由PQCT），之前和之后 12个月的青春期封锁。该项目将利用我们的大量患者人群作为两场研究 全国认可的儿科医院以及我们在DXA，PQCT和MRI/MRS的丰富经验。在 探索目的，我们还将考虑青春期阻滞对焦虑，抑郁和与健康有关的影响 生活质量。拟议研究的发现将使我们能够确定预防策略以应对潜力 青春期封锁的长期不良后遗症，例如早期骨质疏松症和骨折，提高人们对 跨性别青年的提供者，并在收到GnRH激动剂后帮助指导监测。