Serotonin Reuptake Inhibitors and Bone Mineralization in Adolescents

青少年血清素再摄取抑制剂和骨矿化

• 批准号: 7993410
• 负责人: Chadi A. Calarge
• 金额: $ 67.9万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7993410
• 关键词: 17 year old; 20 year old; Accounting; Adolescent; Adult; Adverse effects; Affect; Age; Alkaline Phosphatase; Animals; Architecture; Award; Bone Density; Bone Resorption; Boxing; Cell Differentiation process; Child; Childhood; Clinical Trials; Collagen Type I; Complement; Cyclophosphamide; Development; Elderly; Enrollment; Epidemiologic Studies; Exhibits; Failure; Female; Fracture; Future; Genes; Genetic; Genetic Variation; Genetic screening method; Genotype; Growth; Individual; Intervention; Knowledge; Laboratories; Life; Life Expectancy; Light; Link; Measures; Medicine; Mental disorders; Minerals; Minisatellite Repeats; Mission; Morbidity - disease rate; Mus; National Institute of Mental Health; Observational Study; Osteocalcin; Osteogenesis; Osteoporosis; Participant; Patients; Peripheral; Pharmaceutical Preparations; Pharmacogenetics; Physiologic calcification; Play; Population; Preventive Intervention; Process; Psychiatric therapeutic procedure; Psychopathology; Quality of life; Radial; Recruitment Activity; Research Priority; Risk; Role; Safety; Sampling; Selective Serotonin Reuptake Inhibitor; Serotonin; Sex Distribution; Site; Staging; Sum; System; Testing; Variant; Vertebral column; Vulnerable Populations; Weight-Bearing state; Work; X-Ray Computed Tomography; Youth; age group; bone; bone cell; bone health; bone loss; bone mass; bone metabolism; bone turnover; emerging adult; follow-up; genetic variant; high risk; improved; lifetime risk; male; mortality; pre-clinical; preclinical study; prevent; prospective; public health relevance; receptor; research study; restoration; senescence; serotonin receptor; serotonin transporter; skeletal; treatment duration; young adult

DESCRIPTION (provided by applicant): Bone mass achieved by early adulthood is a major determinant of lifetime risk for osteoporosis. Therefore, optimizing peak bone mass is crucial to avoiding bone fracture with its associated morbidity and mortality. Emerging evidence suggests that serotonin plays a central role in bone metabolism. For example, preclinical experiments have shown that bone cells express the serotonin transporter and a variety of functional serotonin receptors whose activity modulates bone turnover. Epidemiologic studies have linked selective serotonin reuptake inhibitors (SSRIs) to reduced bone mineral density and increased fracture risk in the elderly. SSRIs are widely used in youths to treat a number of psychiatric disorders. However, while their short-term efficacy and safety have been established, their long-term safety remains little investigated. We, here, propose to recruit, in a 2-year prospective observational study, 15 to 20 year-old participants upon the initiation of SSRI treatment. During the period of the Award, bone mineral density of the lumbar spine and whole body will be measured using dual x-ray absorptiometry and of the radius using peripheral quantitative computerized tomography. A detailed psychiatric assessment will be conducted to control for psychopathology, as a potential confounding factor affecting bone mineralization. Changes in psychiatric treatment during the follow up period will also be documented and accounted for. By using a group of healthy controls, of comparable age and sex distribution, we aim to evaluate 1) whether psychopathology, at baseline, is associated with low bone mass, 2) if treatment with SSRIs suppresses bone mineralization, and 3) if the discontinuation of the SSRI is followed by a restoration of bone mineral accrual. 4) Furthermore, genetic testing will investigate whether variants of the serotonin system genes moderate the effect of SSRI treatment on bone mineral density. In sum, this work aims to improve the long-term safety of psychiatric treatments in order to optimize functioning and the quality of life of those who suffer from psychiatric disorders. This is consistent with the mission of the National Institute of Mental Health. PUBLIC HEALTH RELEVANCE: Building on findings from animal studies, pediatric clinical trials, epidemiologic research in adults, and on preliminary findings from our laboratory in children and adolescents, this project aims to investigate whether SSRIs, a group of widely-used psychotropics, are associated with impaired bone mineralization in youths. Establishing such an association is a first step in a process that would eventually involve developing preventative interventions. Identifying genetic factors that place certain youths at higher risks for this side effect would ultimately allow clinicians to tailor treatment to the needs and vulnerabilities of each youth, moving the field closer towards individualized medicine.

描述（由申请人提供）：成年早期达到的骨量是终生骨质疏松症风险的主要决定因素。因此，优化峰值骨量对于避免骨折及其相关的发病率和死亡率至关重要。 新的证据表明，血清素在骨代谢中发挥着核心作用。例如，临床前实验表明，骨细胞表达血清素转运蛋白和多种功能性血清素受体，其活性可调节骨转换。流行病学研究表明，选择性血清素再摄取抑制剂（SSRI）会降低老年人的骨矿物质密度并增加骨折风险。 SSRIs 广泛用于青少年治疗多种精神疾病。然而，虽然它们的短期疗效和安全性已经确定，但其长期安全性仍然很少被研究。 我们在此建议在一项为期 2 年的前瞻性观察研究中招募 15 至 20 岁的参与者，以开始 SSRI 治疗。颁奖期间，将使用双 X 射线骨密度测量仪测量腰椎和全身的骨矿物质密度，并使用外周定量计算机断层扫描测量桡骨的骨矿物质密度。将进行详细的精神病学评估以控制精神病理学，将其作为影响骨矿化的潜在混杂因素。随访期间精神治疗的变化也将被记录并说明。通过使用一组年龄和性别分布相当的健康对照，我们的目的是评估 1) 基线时精神病理学是否与低骨量相关，2) SSRI 治疗是否会抑制骨矿化，以及 3) 停用 SSRI 后是否会恢复骨矿物质累积。 4) 此外，基因检测将调查血清素系统基因的变异是否会调节 SSRI 治疗对骨矿物质密度的影响。 总之，这项工作旨在提高精神治疗的长期安全性，以优化精神疾病患者的功能和生活质量。这与国家心理健康研究所的使命是一致的。 公共健康相关性：基于动物研究、儿科临床试验、成人流行病学研究的结果以及我们实验室在儿童和青少年中的初步研究结果，该项目旨在调查 SSRIs（一组广泛使用的精神药物）是否与青少年骨矿化受损有关。建立这样的协会是最终涉及制定预防性干预措施的过程的第一步。确定使某些青少年面临这种副作用更高风险的遗传因素，最终将使临床医生能够根据每个青少年的需求和脆弱性定制治疗方案，使该领域更接近个体化医疗。