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The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD

骨质疏松症与慢性阻塞性肺病表型异质性的关系

基本信息

批准号：
8519518
负责人：
JESSICA BON
金额：
$ 13.03万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8519518
关键词：
Algorithms Antibodies Attenuated Bioinformatics Biological Factors Biological Markers Biological Response Modifier Therapy Biometry Blocking Antibodies Body mass index Bone Density Bone Diseases Bone Marrow Bone Resorption Categories Cell Count Cell Culture Techniques Chronic Chronic Obstructive Airway Disease Classification Clinical Clinical Trials Collaborations Comorbidity Coronary Arteriosclerosis Cross-Sectional Studies Dentin Development Direct Costs Discipline Disease Disease Progression Ensure Environment Epidemiology Evaluation Evolution Facilities and Administrative Costs Fracture Frequencies Functional disorder Future Gonadal Hormones Heterogeneity Hip region structure Individual Inflammation Inflammation Mediators Inflammatory Instruction Interleukin-6 Laboratories Lead Learning Link Literature Longitudinal Studies Lung Lung diseases Measurement Measures Mediator of activation protein Medical Mentors Modeling Monitor Mononuclear Morbidity - disease rate Multiple Myeloma Natural History Nature Obstruction Oral Osteoclasts Osteogenesis Osteoporosis Outcome Assessment Patients Pattern Peripheral Peripheral Blood Mononuclear Cell Phenotype Physiological Prevalence Principal Investigator Process Pulmonary Emphysema Pulmonary Function Test/Forced Expiratory Volume 1 Research Research Personnel Resources Risk Risk Factors Series Serum Serum Markers Severities Skeletal Muscle Skeletal system Smoker Steroid therapy Steroids Subgroup Techniques Testing Therapeutic Time Training Tumor Necrosis Factor-alpha United States Universities Variant Vertebral column authority base bone loss bone metabolism burden of illness cigarette smoking clinical phenotype cohort disease phenotype driving force experience hormone deficiency inflammatory marker insight knowledge base mortality precursor cell programs research study screening skills symposium time interval

项目摘要

Program Director/Principal Investigator (Last, First, Middle): Bon, Jessica, Marie Project Summary Studies show an increased prevalence of osteoporosis in individuals with chronic obstructive pulmonary disease (COPD), yet an understanding of the true prevalence, clinical implications, and mechanistic relationships remains limited. This proposal will determine the prevalence of decreased bone mineral density (BMD) and accelerated loss of BMD over time and its relationship to markers of bone resorption and formation within spirometrically defined categories of obstruction severity in a large cohort of current and former smokers with wide variability of airflow limitation. Radiographic, clinical, and serum marker phenotypes will be used to construct a classification and prediction model to identify COPD patients at greatest risk for osteoporosis and accelerated loss of BMD over time. Finally, a set of translational experiments will compare osteoclast formation and activity and its relationship to serum inflammatory mediators in COPD patients with and without decreased BMD and accelerated loss of BMD over time. These aims will define the COPD phenotype that should undergo osteoporosis screening, provide insight into the underlying mechanisms relating COPD and osteoporosis, and identify possible targets for screening and therapy. Training Plan: This proposal will provide the candidate with the unique opportunity to cross medical disciplines, expanding her COPD knowledge-base while developing a background in osteoporosis and bone metabolism. Through coursework and conferences, the candidate will acquire advanced training in biostatistics, epidemiology, and bioinformatics. Techniques learned in Dr. Roodman's laboratory through implementation of this proposal will equip the candidate with the skills necessary to communicate effectively during translational collaborations. The resources and experience of mentor Dr. Sciurba, an expert in COPD clinical phenotyping and outcome assessment in clinical trials, and co-mentor Dr. Roodman, an authority on multiple myeloma and bone disease, combined with the robust research environment at the University of Pittsburgh, ensure the candidate's successful evolution to an independent investigator. RELEVANCE (See instructions): The increased prevalence of osteoporosis in patients with COPD likely has both clinical and functional consequences, contributing significantly to disease burden. Limited understanding of the true prevalence, clinical implications and mechanistic relationship of osteoporosis in COPD necessitates a more precise characterization of the of the COPD patient at risk for osteoporosis as well as further elucidation of the clinical and biologic factors linking the lung and skeletal systems.

项目总监/首席研究员（最后、第一、中间）：Bon、Jessica、Marie 项目概要研究表明，慢性阻塞性肺疾病患者骨质疏松症患病率增加疾病（COPD），但了解真实的患病率、临床意义和机制关系仍然有限。该提案将确定骨矿物质减少的患病率密度（BMD）和 BMD 随着时间的推移加速损失及其与骨吸收和骨吸收标志物的关系在大量当前和以前吸烟者的气流受限变化很大。放射学、临床和血清标志物表型将用于构建分类和预测模型，以识别 COPD 患者随着时间的推移，骨质疏松症和骨密度加速损失的风险最大。最后附上一组翻译实验将比较破骨细胞的形成和活性及其与血清炎症的关系随着时间的推移，慢性阻塞性肺病 (COPD) 患者的 BMD 是否下降以及 BMD 加速损失。这些目标将定义应进行骨质疏松症筛查的慢性阻塞性肺病表型，提供见解深入了解慢性阻塞性肺病和骨质疏松症的相关机制，并确定可能的筛查目标和治疗。培训计划：该提案将为候选人提供独特的跨界机会医学学科，扩大她的慢性阻塞性肺病知识库，同时发展骨质疏松症的背景和骨代谢。通过课程和会议，候选人将获得高级培训生物统计学、流行病学和生物信息学。在鲁德曼博士的实验室中通过以下方式学到的技术该提案的实施将使候选人具备有效沟通所需的技能在翻译合作期间。导师COPD专家Sciurba博士的资源和经验临床试验中的临床表型和结果评估，以及联合导师 Roodman 博士，他是该领域的权威多发性骨髓瘤和骨病，结合大学强大的研究环境匹兹堡，确保候选人成功转型为独立调查员。相关性（参见说明）：慢性阻塞性肺病 (COPD) 患者骨质疏松患病率的增加可能具有临床和功能方面的影响后果，显着加重疾病负担。对真实患病率的了解有限， COPD 中骨质疏松的临床意义和机制关系需要更精确的研究具有骨质疏松风险的 COPD 患者的特征以及进一步阐明连接肺和骨骼系统的临床和生物学因素。