The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD

项目主任/首席调查员(最后、第一、中间)：Bon、Jessica、Marie 项目摘要 研究表明慢性阻塞性肺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、临床意义和发病机制 人际关系仍然是有限的。这项建议将确定骨矿物质减少的流行率。 骨密度(BMD)和随时间加速的BMD丢失及其与骨吸收和骨吸收标志物的关系 在一大群海流和肺炎患者中，在肺活量定义的梗阻严重程度类别内形成 前吸烟者的气流限制有很大的可变性。放射学、临床和血清标记物 表型将被用来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丧失的风险最大。最后，一套可翻译的 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 伴有和不伴有BMD降低和随时间加速的BMD丢失的COPD患者中的介质。 这些目标将定义应接受骨质疏松症筛查的COPD表型，提供洞察力 研究慢性阻塞性肺疾病和骨质疏松症的潜在机制，并确定可能的筛查目标 和心理治疗。培训计划：这项建议将为应聘者提供独特的机会 医学学科，扩展她的COPD知识基础，同时发展骨质疏松症背景 和骨骼新陈代谢。通过课程作业和会议，候选人将获得高级培训 在生物统计学、流行病学和生物信息学方面。在鲁德曼博士的实验室里通过 这项提议的实施将使应聘者具备有效沟通所需的技能 在翻译协作期间。慢性阻塞性肺疾病专家肖尔巴博士导师的资源和经验 临床试验中的临床表型和结果评估，以及共同导师Roodman博士，他是 多发性骨髓瘤和骨病，再加上加州大学强大的研究环境 匹兹堡，确保候选人成功演变为独立调查员。 相关性(请参阅说明)： COPD患者骨质疏松症患病率的增加可能有临床和功能两方面的原因 造成严重后果，大大加重了疾病负担。对真实流行率的了解有限， COPD患者骨质疏松的临床意义和机制关系需要更精确的研究 有骨质疏松症风险的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.