Examining the Skeletal Effects of Psychostimulants

检查精神兴奋剂对骨骼的影响

• 批准号: 10439840
• 负责人: Chadi A. Calarge
• 金额: $ 60.48万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-20 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439840
• 关键词: 11 year old; 16 year old; 17 year old; 19 year old; Accounting; Adolescent; Adolescent and Young Adult; Affect; Aftercare; Age; Amphetamines; Antipsychotic Agents; Attention deficit hyperactivity disorder; Bone Density; Bone Mineral Contents; Bone Resorption; Child; Chronic; Confounding Factors (Epidemiology); Control Groups; Cross-Sectional Studies; Data; Data Set; Development; Diagnosis; Distal; Dose; Drug Prescriptions; Dual-Energy X-Ray Absorptiometry; Enrollment; Failure; Family; Female; Funding; Growth; Height; Hip region structure; Impairment; Intervention; Knowledge; Life; Longitudinal Studies; Longitudinal observational study; Masks; Mediating; Medical; Minerals; Monitor; National Health and Nutrition Examination Survey; Neck; Observational Study; Osteoclasts; Outcome; Participant; Patients; Peripheral; Pharmaceutical Preparations; Physical activity; Polypharmacy; Prevalence; Prospective Studies; Psychopathology; Puberty; Publishing; Race; Radial; Rattus; Resolution; Risk; Risperidone; Ritalin; Scanning; Selective Serotonin Reuptake Inhibitor; Vertebral column; Vitamin D; X-Ray Computed Tomography; age group; base; bone; bone fragility; bone mass; bone quality; bone strength; boys; calcium intake; clinically significant; comparison group; cortical bone; critical developmental period; design; fracture risk; girls; male; medication safety; pre-clinical research; preference; prepuberty; prospective; psychostimulant; secondary analysis; sex; skeletal; stimulant use; substantia spongiosa; tibia; young adult

PROJECT SUMMARY Psychostimulants used to treat attention deficit hyperactivity disorder (ADHD) are the second most prescribed medication class for long-term use in children and adolescents. These medications have long been known to impede linear growth, however, recent preclinical research has shown that they also reduce appendicular bone mineral content (BMC) and bone quality in young rats. This is mediated by an increase in osteoclast differentiation and activity, promoting bone resorption. In children and adolescents, the use of psychostimulants has also been associated with clinically significant lower dual-energy x-ray absorptiometry (DXA)-based BMC and areal bone mineral density (aBMD) at the lumbar spine (LS) and hip, in a dose- dependent manner. In addition, our group has found that boys chronically-treated with psychostimulants may have lower LS aBMD velocity Z-scores compared to those not taking psychostimulants. Given that bone mass accrued by young adulthood may determine fracture risk later in life, this application seeks to examine the skeletal effects of psychostimulants in children and adolescents and examine whether sex and pubertal development are significant moderators. Specifically, we propose to enroll otherwise medically healthy 7 to 16 year-olds within one month of starting psychostimulants and unmedicated. In this observational study, we will monitor skeletal outcomes over a one-year period, with repeated DXA and high- resolution pQCT (HRpQCT) scans, along with a thorough assessment of psychopathology and of factors known to affect bone mineral accrual. This design will allow us to prospectively asses the effects of psychostimulants on bone mass accrual and bone microarchitecture in children and adolescents (Aim 1). Given that peak bone accrual velocity in boys is nearly double that in girls and that that bone mass increases exponentially during puberty, we also seek to evaluate whether sex and stages of sexual maturity moderate this effect (Aim 2). Secondary analyses will examine the impact of these medications on additional DXA- and HRpQCT-based outcomes. This study will be the first to prospectively examine whether psychostimulants impair bone mineral accrual during purberty, increasing one's risk for low bone mass later in life. This information is key to designing appropriate interventions to mitigate this risk and to helping clinicians and families make informed decisions about treatment options most suitable for the patient's needs.

项目摘要 用于治疗注意缺陷多动障碍（ADHD）的精神兴奋剂是第二大 儿童和青少年长期使用的处方药类别。这些药物长期以来 但是，最近临床前研究表明，它们也能减少 测定幼鼠骨矿物质含量（BMC）和骨质量。这是通过增加 破骨细胞分化活跃，促进骨吸收。在儿童和青少年中， 精神兴奋剂也与临床上显著较低的双能X线吸收测定法相关 （DXA）的BMC和面积骨矿物质密度（aBMD）在腰椎（LS）和髋关节，在剂量- 依赖的方式。此外，我们的研究小组发现，长期接受精神兴奋剂治疗的男孩可能 与未服用精神兴奋剂的患者相比，LS aBMD速度Z评分较低。 考虑到年轻时积累的骨量可能决定以后生活中的骨折风险， 旨在研究精神兴奋剂对儿童和青少年骨骼的影响， 性别和青春期发育是重要的调节因素。具体来说，我们建议以其他方式录取 医学上健康的7至16岁儿童在开始精神兴奋剂和未用药的一个月内。在这 观察性研究，我们将监测骨骼的结果超过一年的时间，重复DXA和高， 分辨率pQCT（HRpQCT）扫描，沿着对精神病理学和因素的全面评估 已知会影响骨矿物质积累。这种设计将使我们能够前瞻性地评估 精神兴奋剂对儿童和青少年骨量增加和骨微结构的影响（目的1）。 鉴于男孩的峰值骨增长速度几乎是女孩的两倍， 在青春期呈指数增长，我们还试图评估性别和性成熟阶段是否适度 这一效果（目标2）。次要分析将检查这些药物对额外DXA的影响， 基于HRpQCT的结果。 这项研究将是第一个前瞻性地研究精神兴奋剂是否会损害骨矿物质的积累 在青春期，增加了一个人在以后的生活中骨质疏松的风险。这些信息是设计 适当的干预措施，以减轻这种风险，并帮助临床医生和家庭作出明智的决定 最适合患者需求的治疗方案。