Examining the Skeletal Effects of Psychostimulants

项目总结 用于治疗注意缺陷多动障碍(ADHD)的精神刺激剂排在第二位 儿童和青少年长期使用的处方药物类别。长期以来，这些药物一直是 然而，已知会阻碍线性增长，最近的临床前研究表明，它们也会减少 幼年大鼠附件骨矿物质含量与骨质量的关系。这是由增加的 破骨细胞分化活跃，促进骨吸收。在儿童和青少年中，使用 心理刺激剂也与临床上较低的双能x射线吸收测量法有关。 基于(DXA)的BMC和腰椎(LS)和髋部的面骨密度(ABMD)，在一定剂量- 依赖的态度。此外，我们小组发现，长期接受精神刺激剂治疗的男孩可能会 与不服用精神刺激剂的人相比，有较低的LS aBMD速度Z得分。 考虑到青壮年积累的骨量可能决定晚年的骨折风险，这一应用程序 旨在研究精神刺激剂对儿童和青少年的骨骼影响，并检查 性和青春期发育是重要的调节因素。具体地说，我们建议以其他方式注册 身体健康的7至16岁的儿童，在服用精神刺激剂后一个月内不服药。在这 观察性研究，我们将在一年内监测骨骼结果，重复DXA和高- 分辨率pQCT(HRpQCT)扫描，以及对精神病理学和因素的彻底评估 已知会影响骨矿物质的积累。这一设计将使我们能够前瞻性地评估 心理刺激剂对儿童和青少年骨量增加和骨微结构的影响(目标1)。 鉴于男孩的骨峰值速度几乎是女孩的两倍，而且骨量增加 在青春期，我们还试图评估性行为和性成熟阶段是否适中 此效果(目标2)。二次分析将检查这些药物对额外的DXA-和 基于HRpQCT的结果。 这项研究将首次前瞻性地研究精神刺激剂是否会损害骨矿物质的积累。 在青春期，增加了一个人在晚年患低骨量的风险。这些信息是设计的关键 适当的干预措施，以减少这种风险，并帮助临床医生和家庭做出明智的决定 关于最适合患者需求的治疗方案。

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.