The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD

描述（由申请人提供）：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，但对真实患病率、临床意义和机制关系的理解仍然有限。本提案将在一个大型队列中确定骨矿物质密度（BMD）降低和BMD随时间加速丢失的患病率，以及其与肺量计定义的阻塞严重程度类别内的骨吸收和形成标志物的关系，该队列中的当前和既往吸烟者具有广泛的气流限制变异性。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，以识别骨质疏松症风险最高和BMD随时间加速丢失的COPD患者。最后，一组转化实验将比较破骨细胞形成和活性及其与COPD患者血清炎症介质的关系，这些患者有和没有BMD降低和BMD随时间的加速损失。这些目标将定义应接受骨质疏松症筛查的COPD表型，深入了解COPD和骨质疏松症相关的潜在机制，并确定筛查和治疗的可能靶点。培训计划：该提案将为候选人提供跨医学学科的独特机会，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的高级培训。通过实施本提案，在Roodman博士的实验室学到的技术将使候选人具备在翻译合作期间有效沟通所需的技能。导师Sciurba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Roodman博士是多发性骨髓瘤和骨病方面的权威，其资源和经验与匹兹堡大学强大的研究环境相结合，确保候选人成功发展为独立研究者。 (End摘要）

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)