Skeletal Health and Bone Marrow Composition Among Youth

青少年骨骼健康和骨髓成分

• 批准号: 10401768
• 负责人: CATHERINE M. GORDON
• 金额: $ 58.29万
• 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/10401768
• 关键词: Address; Adipocytes; Adolescence; Adolescent; Adult; Adverse effects; Affect; Age; Agonist; Anxiety; Awareness; Beck depression inventory; Birth; Body mass index; Bone Density; Bone Marrow; Bone structure; Child; Child Health; Clinical Assessment Tool; Data; Development; Disease Progression; Distress; Dual-Energy X-Ray Absorptiometry; Eating Disorders; Equipment and supply inventories; Estrogens; Ethnic Origin; Fatty acid glycerol esters; Feeling; Female; Fracture; Gender; Geometry; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Health; Hematopoietic; Hormonal; Hormones; Intervention; Lipids; Long-Term Effects; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Marrow; Measurement; Measures; Medical; Mental Depression; Mental Health; Mesenchymal Stem Cells; Monitor; Obesity; Osteoblasts; Osteogenesis; Osteoporosis; Outcome; Participant; Patient Self-Report; Pediatric Hospitals; Peripheral; Phase; Prevention strategy; Professional Organizations; Provider; Puberty; Questionnaires; Race; Research; Research Personnel; Sex Characteristics; Site; Skeleton; Spectrum Analysis; Structure; Testosterone; Time; Translating; Well in self; Work; X-Ray Computed Tomography; Yellow Marrow; Youth; bone; bone health; bone mass; clinically relevant; clinically significant; cohort; critical period; experience; fracture risk; gender dysphoria; health related quality of life; hormone therapy; insight; male; patient population; physical conditioning; recruit; restrictive eating; sex; skeletal; spectroscopic imaging; tool; trait; 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.

摘要