Emphysema and Inflammatory Biomarkers and Risk of Osteoporosis in Men with COPD

肺气肿和炎症生物标志物以及男性慢性阻塞性肺病患者骨质疏松症的风险

• 批准号: 9551566
• 负责人: JESSICA BON
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9551566
• 关键词: Acute; Address; Alveolar Macrophages; Animal Model; Antibodies; Autoantibodies; Autoantigens; Autoimmune Process; Autoimmunity; Binding; Biological Markers; Bone Density; Bone Resorption; Cachexia; Cells; Chronic Obstructive Airway Disease; Consensus; Data; Diagnostic radiologic examination; Endoplasmic Reticulum; Female; Fibrinogen; Fracture; Frequencies; Future; Goals; Guidelines; Health; Hip Fractures; Human; IL6 gene; Immunologics; Incidence; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukin-6; Knowledge; Link; Literature; Longitudinal cohort; Low Prevalence; Measures; Mediating; Molecular Chaperones; Morbidity - disease rate; Obstructive Lung Diseases; Osteoclasts; Osteoporosis; Osteoporosis prevention; Pathogenesis; Pathogenicity; Pathologic; Patients; Play; Population; Prevalence; Prevention strategy; Process; Production; Proteins; Public Health; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Risk; Risk Factors; Roentgen Rays; Role; Smoker; Spinal Fractures; Steroids; Symptoms; Testing; Time; Translations; Veterans; Woman; X-Ray Computed Tomography; bone; bone loss; bone turnover; circulating biomarkers; endoplasmic reticulum stress; epidemiology study; glucose-regulated proteins; human model; insight; male; men; mortality; novel; osteoporosis with pathological fracture; osteoporotic bone; physical inactivity; precursor cell; predictive marker; promoter; prospective test; public health relevance; pulmonary function; response; screening; skeletal; targeted treatment; time interval; treatment strategy

 DESCRIPTION (provided by applicant): Low bone mineral density (BMD) is associated with chronic obstructive lung disease (COPD) independent of traditional osteoporosis risk factors, including physical inactivity, steroid use, ad cachexia. However, osteoporosis in men with COPD is often underdiagnosed due to lack of consensus on osteoporosis screening guidelines in this group of patients. Systemic inflammation plays a key role in the pathogenesis of both COPD and osteoporosis; but few studies have shown a relationship between specific systemic inflammatory biomarkers and either low BMD or accelerated loss of BMD over time. Immunologic alterations likewise contribute to the pathogenesis of both COPD and osteoporosis but the role of autoimmunity in COPD-related osteoporosis has not been studied. An independent association between low BMD and emphysema has been supported by the literature, but the mechanism for this association is unknown. This project's overall goal is to identify specific systemic inflammatory and autoimmune processes associated with both concurrent and progressive BMD loss and emphysema in men with COPD. This goal will be accomplished by establishing a two-year longitudinal c o h o r t o f m e n w i t h C O P D and attaining baseline and two-year assessments of BMD, radiographic emphysema, a n d pulmonary function. Inflammatory biomarker levels will be measured at six month intervals and during episodes of acute exacerbation of COPD (AECOPD). Systemic inflammatory and autoimmune biomarkers associated with BMD loss, measured by dual x-ray absorptiometry, emphysema progression, measured by quantitative CT scan, and incident hip or vertebral fractures over the two-year time interval will be identified. Changes in systemic inflammatory and autoimmune biomarker levels with AECOPD and the relationship to bone turnover and cumulative BMD loss will also be assessed. The findings from this project will identify criteria for male COPD patients at risk of accelerated BMD loss in whom early and serial BMD assessments may be beneficial, provide insight into pathogenic mechanisms linking COPD and osteoporosis, and provide novel targets for osteoporosis prevention and treatment strategies in men with COPD. This project will also address an unmet public health need given that most data on skeletal health are in women.

 描述（由申请人提供）： 低骨矿物质密度 (BMD) 与慢性阻塞性肺病 (COPD) 相关，独立于传统的骨质疏松症危险因素，包括身体活动不足、类固醇使用、恶病质。然而，由于对这组患者的骨质疏松症筛查指南缺乏共识，患有慢性阻塞性肺病的男性骨质疏松症经常被诊断不足。全身炎症在慢性阻塞性肺病和骨质疏松症的发病机制中起着关键作用；但很少有研究表明特定的全身炎症生物标志物与低 BMD 或随着时间的推移 BMD 加速损失之间存在关系。免疫学改变同样导致慢性阻塞性肺病和骨质疏松症的发病机制，但自身免疫在慢性阻塞性肺病相关骨质疏松症中的作用尚未研究。文献支持低 BMD 与肺气肿之间存在独立关联，但这种关联的机制尚不清楚。该项目的总体目标是确定与 COPD 男性并发和进行性 BMD 损失和肺气肿相关的特定全身炎症和自身免疫过程。这一目标将通过建立慢性阻塞性肺病患者的两年纵向队列并获得 BMD、放射学肺气肿和肺功能的基线和两年评估来实现。将每隔六个月以及在慢性阻塞性肺病急性加重 (AECOPD) 发作期间测量炎症生物标志物水平。将确定与 BMD 损失（通过双 X 射线骨密度测定法测量）、肺气肿进展（通过定量 CT 扫描测量）以及两年时间间隔内发生的髋部或椎骨骨折相关的全身炎症和自身免疫生物标志物。还将评估 AECOPD 引起的全身炎症和自身免疫生物标志物水平的变化以及与骨转换和累积 BMD 损失的关系。该项目的研究结果将确定具有加速 BMD 损失风险的男性 COPD 患者的标准，对这些患者进行早期和连续的 BMD 评估可能是有益的，深入了解 COPD 和骨质疏松症之间的致病机制，并为患有 COPD 的男性骨质疏松症预防和治疗策略提供新的目标。鉴于大多数骨骼健康数据都来自女性，该项目还将解决未满足的公共卫生需求。