Skeletal Health and Bone Marrow Composition Among Youth

摘要 患有性别焦虑症的跨性别青年经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 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成脂肪细胞，而不是成骨细胞， 青少年和成人的骨生成、骨形成和骨密度。目前的调查人员已经 先前的研究表明，患有限制性饮食障碍和雌激素水平低下的青少年 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 骨髓变化可能对骨形成、骨增生和骨再生有长期的不利影响。 青春期，最终，终身骨骼健康。检查骨髓成分如何改变后， 跨性别青年的青春期阻滞及其与骨密度、结构和横截面的关系 几何学，可以提供一个机制的理解，促性腺激素释放激素激动剂对年轻，不成熟的 骷髅这项提案将研究青春期阻滞对骨骼的影响，青春期阻滞是变性的最初阶段。 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。的 这项研究将为跨性别青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）和波谱（MRS）。这些结果将与骨密度相关 通过临床评估工具，双能X射线吸收测定法（DXA）和 外周定量计算机断层扫描（pQCT）。我们还将讨论临床上 骨髓成分与年轻人骨密度和骨骼强度关系的相关问题 青春期受阻的青少年。我们将招募一批青少年， 出生时指定为女性（AFAB）和出生时指定为男性（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， 在青春期阻滞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人群，在国家认可的儿科医院和我们的 DXA、pQCT和MRI/MRS的丰富经验。在探索性目的中，我们还将考虑 青春期阻断焦虑、抑郁和健康相关生活质量。拟议研究的结果 将使我们能够确定预防策略，以应对潜在的长期不良后遗症的青春期 阻断，如早期骨质疏松症和骨折，提高跨性别青年的供应商的认识， 帮助指导接受GnRH激动剂后的监测。

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.