Skeletal Health and Bone Marrow Composition in Transgender 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质细胞 干细胞优先分化成脂肪细胞，而不是成骨细胞， 形成和骨密度在青少年和成人。目前的调查人员此前曾 研究表明，患有限制性饮食障碍和雌激素分泌不足的青少年的骨髓 随着疾病的进展，骨髓从红色（造血）变为黄色（脂肪）。这些骨髓变化 可能对骨形成、青春期的骨增生有长期的不利影响，最终， 终身骨骼健康。研究青春期阻滞后骨髓成分如何改变， 跨性别青年，以及它与骨密度，结构和横截面几何形状的关系，可以提供一个 对GnRH激动剂对年轻、未成熟骨骼影响的机制性理解。这项建议会 检查青春期阻滞的骨骼影响，这是跨性别医疗管理的初始阶段， 性别肯定激素治疗（雌激素或睾酮治疗）。这项研究将提供新的见解， 变性青年的骨骼健康，通过磁共振成像（MRI）检查骨髓成分 光谱学（MRS）这些结果将与通过临床试验获得的BMD测量结果相关。 评估工具双能X线吸收测定法（DXA）和研究工具外周定量 计算机断层扫描（pQCT）。我们还将讨论骨髓如何与临床相关的问题， 本发明涉及正经历青春期的年轻青少年的骨密度和骨骼强度 封锁我们将招募一组青少年，包括出生时指定为女性（AFAB）的青少年和 出生时的男性（AMAB）和匹配的健康对照，并检查骨髓组成（通过MRI/MRS）， 术前和术后的骨密度（DXA + pQCT）、骨结构和横截面几何形状（pQCT） 12个月的青春期封锁。该项目将利用我们庞大的患者人群作为一个双中心研究， 我们在DXA、pQCT和MRI/MRS方面拥有丰富的经验。 为了探索性的目的，我们还将考虑青春期阻滞对焦虑，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战略，以应对潜在的 青春期阻滞的长期不良后遗症，如早期骨质疏松症和骨折，提高对 提供者的跨性别青年，并帮助指导监测后收到的GnRH激动剂。

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.