The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD

描述(申请人提供)：研究表明慢性阻塞性肺疾病(COPD)患者骨质疏松症的患病率增加，但对其真实患病率、临床意义和发病机制的了解仍然有限。这项建议将确定随着时间的推移，骨密度降低和骨密度加速丧失的流行率，以及它与呼吸节律定义的梗阻严重程度中骨吸收和形成的标志物的关系，在一大群现吸烟者和既往吸烟者中，空气流动限制的差异很大。放射学、临床和血清标志物表型将被用来构建一个分类和预测模型，以确定COPD患者随着时间的推移有最大的骨质疏松症和骨密度加速丧失的风险。最后，一组翻译实验将比较COPD患者中破骨细胞的形成和活性及其与血清炎症介质的关系，这些患者有或没有随着时间的推移骨密度下降和骨密度加速丢失。这些目标将定义应接受骨质疏松症筛查的COPD表型，提供与COPD和骨质疏松症相关的潜在机制的洞察，并确定可能的筛查和治疗靶点。培训计划：这项建议将为候选人提供一个独特的跨医学学科的机会，扩大她的COPD知识基础，同时发展骨质疏松症和骨代谢的背景。通过课程和会议，候选人将获得生物统计学、流行病学和生物信息学方面的高级培训。在Roodman博士的实验室中通过实施这项提议所学到的技术将使应聘者具备在翻译合作中有效沟通所需的技能。导师肖尔巴博士是COP临床表型和临床试验结果评估方面的专家，共同导师鲁德曼博士是多发性骨髓瘤和骨骼疾病方面的权威，他们的资源和经验加上匹兹堡大学强大的研究环境，确保了候选人成功地演变为一名独立的研究人员。(摘要结束)

DESCRIPTION (provided by applicant): 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 COP 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. (End of Abstract)