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

 描述(由申请人提供)： 低骨密度(BMD)与慢性阻塞性肺疾病(COPD)相关，与传统的骨质疏松症危险因素无关，包括缺乏运动、类固醇使用、恶病质。然而，由于对这类患者的骨质疏松筛查指南缺乏共识，COPD男性患者的骨质疏松往往被低估。全身炎症在COPD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或随时间推移加速的BMD丢失之间存在关系。免疫改变同样导致COPD和骨质疏松症的发病，但自身免疫在COPD相关性骨质疏松症中的作用尚未被研究。低骨密度与肺气肿之间的独立关联已得到文献的支持，但这种关联的机制尚不清楚。该项目的总体目标是确定与慢性阻塞性肺疾病男性患者并发和进行性骨密度丢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两年纵向对照和获得基线和两年的骨密度、放射学肺气肿和肺功能评估来实现。炎症生物标记物水平将每隔6个月和慢性阻塞性肺病急性加重(AECOPD)期间进行测量。系统炎症和自身免疫生物标记物与骨密度丢失、肺气肿进展、定量CT扫描和两年时间间隔内的髋部或脊椎骨折有关。还将评估AECOPD患者全身炎症和自身免疫生物标记物水平的变化，以及与骨转换和累积骨密度丢失的关系。该项目的发现将为有加速骨密度丢失风险的男性COPD患者确定早期和连续骨密度评估可能有益的标准，为COPD和骨质疏松症的发病机制提供洞察，并为男性COPD患者的骨质疏松症预防和治疗策略提供新的靶点。该项目还将解决未得到满足的公共卫生需求，因为有关骨骼健康的大多数数据都在妇女身上。

 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.