Bone Density, Structure, and Estimated Strength in Transgender Youth Receiving Pubertal Suppression in Early Puberty

青春期早期接受青春期抑制的跨性别青少年的骨密度、结构和估计强度

• 批准号: 10269888
• 负责人: Janet Yi Man Lee
• 金额: $ 2.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10269888
• 关键词: 25-hydroxyvitamin D; Adolescent; Age; Agonist; Area; Attenuated; Biometry; Body Composition; Body measure procedure; Bone Density; Bone Development; Bone Growth; Bone Resorption; C-telopeptide; Caring; Child Care; Childhood; Clinical; Cohort Studies; Complex; Coupled; Data; Data Analyses; Densitometry; Diagnostic radiologic examination; Dietary Calcium; Drops; Dual-Energy X-Ray Absorptiometry; Elderly; Endocrinology; Enrollment; Ensure; Epidemiology; Estradiol; European; Exercise; Fellowship; Fracture; Future; Gender; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Growth; Guidelines; Health; Hormones; Image; Impairment; Incidence; Insulin-Like Growth Factor I; Intervention; Investigation; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Learning; Life; Measures; Medical; Mental Health; Mentorship; N-terminal; Osteogenesis; Outcome; Participant; Peripheral; Physicians; Physiological; Procollagen; Puberty; Radiology Specialty; Reference Values; Reporting; Research; Resolution; Risk; Scientist; Site; Skeletal Development; Skeletal bone; Skeleton; Structure; Testing; Testosterone; Time; Training; Treatment Protocols; Vitamin D; Weight-Bearing state; Work; X-Ray Computed Tomography; Youth; age related; attenuation; bone; bone age; bone health; bone imaging; bone mass; bone metabolism; bone quality; bone strength; bone turnover; boys; calcium intake; clinical care; clinical practice; design; diet and exercise; experience; fracture risk; gender dysphoria; gender nonconforming; girls; hormone therapy; improved; intervention effect; lean body mass; mineralization; prevent; primary outcome; secondary outcome; sex; skeletal; transgender; young adult

PROJECT SUMMARY/ABSTRACT Access to and demand for gender-affirming medical therapy for gender non-conforming youth have increased, but understanding of the ramifications of these therapies on bone development and skeletal health has lagged behind. Current guidelines recommend treatment of gender dysphoria as early as Tanner Stage 2 with gonadotropin-releasing hormone agonists for puberty suppression, but little is known about the skeletal effects of this intervention. Puberty is a key period of skeletal vulnerability, as rapid longitudinal bone growth coupled with a lag in mass accrual results in decreased bone strength and increased fracture incidence. Peak bone mass, achieved during puberty and young adulthood, largely determines age-related fractures in later life. One European group has demonstrated attenuation of bone mineral density (BMD) accrual after pubertal suppression in older transgender adolescents that did not recover despite subsequent gender-affirming hormone therapy. Major determinants of bone health such as body composition, vitamin D status, weight- bearing exercise, and dietary calcium intake were not assessed. The skeletal effects of puberty suppression in early pubertal transgender youth have never been reported. The objective of this fellowship proposal is to examine measures of bone mass and quality during pubertal suppression in early pubertal transgender youth and to correlate these bone measures with major determinants of bone health. Dr. Lee has designed the proposed longitudinal observational cohort study, during which she will collect and analyze anthropometric, laboratory, and imaging data. We hypothesize that BMD, bone microarchitecture, and bone strength estimates will have attenuated accrual in early pubertal transgender youth after one year of pubertal suppression when compared to puberty-matched, non-transgender, control youth. Dr. Lee's proposed research to test this this hypothesis will concurrently provide training in the use and interpretation of pediatric bone densitometry (Aim 1) and high-resolution peripheral quantitative computed tomography (Aim 2). She will additionally perform complex longitudinal data analyses to determine the relationships between major determinants of skeletal development and bone mass, microarchitecture, and strength (Aim 3). These results will inform current clinical practices and lead to longer-term studies and investigations of interventions to mitigate the expected lag in skeletal development during pubertal suppression. Ultimately, this research will positively contribute to the clinical care of transgender youth. Dr. Lee is training to become a physician-scientist at the intersection of bone metabolism and gender- affirming therapy, a highly relevant area in need of rigorous investigation. Her mentorship team is comprised of experts in endocrinology, radiology, epidemiology, and biostatistics. They will ensure that Dr. Lee fulfills her training goals in advanced skeletal imaging, complex longitudinal data analysis, and the endocrinology of bone and transgender care, which will bolster her application for career development award.

项目摘要/摘要 访问和需求对性别不符合性别的年轻人的性别提供医疗疗法已有 增加，但了解这些疗法对骨骼发育和骨骼健康的影响 落后了。当前的指南建议早在坦纳第2阶段就治疗性别烦躁不安 促性腺激素释放激素激动剂以抑制青春期，但对骨骼知之甚少 这种干预的影响。青春期是骨骼脆弱性的关键时期，因为纵向骨生长迅速 结合质量应计的滞后，导致骨强度降低和骨折发生率增加。顶峰 在青春期和成年期间实现的骨骼质量在很大程度上决定了以后与年龄有关的骨折。 一个欧洲群体表明，青春期后的骨矿物质密度（BMD）衰减 尽管有性别证明 激素疗法。骨骼健康的主要决定因素，例如身体成分，维生素D状态，体重 - 轴承运动和饮食钙摄入量未评估。青春期抑制的骨骼影响 青春期早期的跨性别青年从未得到报道。该奖学金建议的目的是 检查青春期早期青春期抑制期间骨骼质量和质量的测量 变性青年，将这些骨骼测量与骨骼健康的主要决定因素相关联。博士 Lee设计了拟议的纵向观察队列研究，在此期间她将收集和 分析人体测量学，实验室和成像数据。我们假设BMD，骨微结构， 和骨骼强度估计将减弱青春期早期的跨性别青年的应计 与青春期匹配的，非变形者，控制青年相比，青春期抑制的一年。博士 Lee提出的研究旨在检验这一假设的研究将同时提供使用的培训 小儿骨密度测定法（AIM 1）和高分辨率外周定量计算的解释 断层扫描（AIM 2）。她还将执行复杂的纵向数据分析以确定 骨骼发育的主要决定因素与骨骼质量，微体系结构和 力量（目标3）。这些结果将为当前的临床实践提供依据，并导致长期研究 对青春期期间骨骼发育中预期滞后的干预措施的调查 抑制。最终，这项研究将对跨性别青年的临床护理做出积极贡献。 李博士正在训练成为骨骼代谢和性别交集的医师科学家 确认疗法，这是一个需要严格研究的高度相关领域。她的指导团队由 内分泌，放射学，流行病学和生物统计学专家。他们将确保李博士履行她 高级骨骼成像，复杂的纵向数据分析和骨骼内分泌学的训练目标 和Transgender Care，这将加强她的职业发展申请奖。