The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD

项目负责人/主要研究者（最后，第一，中间）：Bon，Jessica，玛丽 项目摘要 研究表明，慢性阻塞性肺疾病患者骨质疏松症的患病率增加 疾病（COPD），但了解真正的患病率，临床意义和机制， 关系仍然有限。这项提案将确定骨矿物质减少的患病率 骨密度（BMD）和BMD随时间的加速损失及其与骨吸收标志物的关系， 在一个大的队列中， 曾吸烟者，气流受限的变异性很大。影像学、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， 骨质疏松症的风险最大，随着时间的推移，BMD会加速流失。最后，一组平移 实验将比较破骨细胞的形成和活性及其与血清炎症因子的关系， 在COPD患者中，BMD降低和BMD随时间加速损失的介质。 这些目标将定义应接受骨质疏松症筛查的COPD表型， 了解COPD和骨质疏松症相关的潜在机制，并确定可能的筛查目标 和心理治疗培训计划：此建议书将为候选人提供一个独特的机会， 医学学科，扩大她的COPD知识基础，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里学到的技术， 实施这一建议将使候选人具备有效沟通的必要技能 在翻译合作中。导师慢性阻塞性肺疾病专家Sciurba博士的资源和经验 临床试验中的临床表型和结果评估，以及共同导师Roodman博士， 多发性骨髓瘤和骨骼疾病，结合强大的研究环境，在大学 匹兹堡，确保候选人成功发展为独立调查员。 相关性（参见说明）： COPD患者骨质疏松症患病率的增加可能具有临床和功能两方面的原因， 严重影响了疾病负担。对真正的患病率了解有限， COPD患者骨质疏松症的临床意义和机制关系需要更精确的 具有骨质疏松症风险的COPD患者的表征以及进一步阐明 连接肺和骨骼系统的临床和生物学因素。

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.