Skeletal Health and Bone Marrow Composition in Transgender Youth

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。性激素抑制可改变间充质 干细胞优先分化为脂肪细胞，而不是成骨细胞，从而影响成骨、骨 青少年和成年人的骨形成和骨密度。现任调查人员此前曾 证明了患有限制性饮食障碍和雌激素减退的青少年会经历骨髓 随着疾病的发展，骨髓从红色(造血细胞)转变为黄色(脂肪)。这些骨髓改变 可能会对青春期的骨形成、骨生长产生不利的长期影响，最终， 终生骨骼健康。青春期封闭后骨髓成分改变的研究 变性人青年及其与骨密度、结构和横断面几何的关系可以提供 从机理上理解促性腺激素释放激素激动剂对年轻、未成熟骨骼的影响。这项提议将 检查青春期封锁对骨骼的影响，青春期封锁是变性人医疗管理的初始阶段，在 性别肯定荷尔蒙治疗(雌激素或睾酮治疗)。这项研究将为我们提供新的见解 变性人青年的骨骼健康，通过磁共振成像(MRI)检查骨髓成分 和光谱学(MRS)。这些结果将与临床获得的骨密度测量结果相关联。 评估工具，双能X射线吸收法(DXA)，以及研究工具，外周定量 计算机断层扫描(PQCT)。我们还将解决与临床相关的问题，即骨髓如何 青春期青少年的骨组成与骨密度和骨骼强度有关 封锁。我们将招募一批青少年，包括那些被分配为出生时女性(AFAB)和被分配到 出生时男性(AMAB)和匹配的健康对照组，并检查骨髓成分(通过MRI/MRS)， 治疗前后的骨密度(通过DXA+pQCT)以及骨结构和横截面几何(通过pQCT) 12个月的青春期封锁。该项目将利用我们庞大的患者群体作为两个站点的研究 国家认可的儿科医院和我们在DXA、pQCT和MRI/MRS方面的丰富经验 探索性目的，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，以应对潜在的 青春期封锁的长期不良后遗症，如早期骨质疏松症和骨折，提高人们对 在接受促性腺激素激动剂后，帮助指导监测。

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.