Skeletal Health and Bone Marrow Composition in Transgender Youth

跨性别青年的骨骼健康和骨髓成分

基本信息

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
项目类别：
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

项目摘要

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，从而损害成骨、骨青少年和成人的骨形成和骨密度。目前的调查人员此前已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骨髓随着疾病的进展，骨髓从红色（造血）变为黄色（脂肪）骨髓。这些骨髓变化可能对青春期的骨形成、骨增生产生不利的长期影响，并最终，终生骨骼健康。检查青春期封锁后骨髓成分如何改变跨性别青年及其与骨密度、结构和横截面几何形状的关系可以提供从机制上理解 GnRH 激动剂对年轻、不成熟骨骼的影响。该提案将检查青春期封锁对骨骼的影响，这是跨性别医疗管理的初始阶段，之前性别肯定激素疗法（雌激素或睾酮疗法）。该研究将提供新的见解跨性别青少年的骨骼健康，通过磁共振成像 (MRI) 检查骨髓成分和光谱（MRS）。这些结果将与临床获得的 BMD 测量值相关联。评估工具，双能 X 射线吸收测定法 (DXA)，以及研究工具，外周定量计算机断层扫描 (pQCT)。我们还将解决骨髓如何成分与青春期青少年的骨密度和骨骼强度有关封锁。我们将招募一批青少年，包括出生时被指定为女性 (AFAB) 和被指定为女性的青少年出生时为男性 (AMAB)，并匹配健康对照，并检查骨髓成分（通过 MRI/MRS），之前和之后的骨密度（通过 DXA + pQCT）以及骨结构和横截面几何形状（通过 pQCT）青春期封锁12个月。该项目将利用我们庞大的患者群体作为一项两中心研究国家认可的儿科医院以及我们在 DXA、pQCT 和 MRI/MRS 方面的丰富经验。在一个作为探索性目标，我们还将考虑青春期封锁对焦虑、抑郁和健康相关的影响生活质量。拟议研究的结果将使我们能够确定预防策略来应对潜在的青春期阻断的长期不良后遗症，如早期骨质疏松和骨折，提高对青春期阻断的认识跨性别青少年的提供者，并帮助指导接受 GnRH 激动剂后的监测。