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.

Public Health Relevance

Although the prevalence of low bone mineral density (BMD) is increased in men with chronic obstructive pulmonary disease (COPD), a consensus on osteoporosis screening criteria in men with obstructive lung disease does not exist. Epidemiologic studies of male veterans with COPD have shown a high rate of hip fracture with rare BMD assessment or osteoporosis treatment. Male veterans hospitalized with hip fractures have higher mortality rates than females. This project will identify systemic inflammatory and autoimmune biomarkers predictive of rapid BMD loss in male COPD patients that may be combined with dual x-ray BMD assessment to identify men at greatest risk for osteoporotic fracture. This project will also investigate the mechanisms linking COPD and osteoporosis that may serve as possible targets for future therapies.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Endocrinology B (ENDB)
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Veterans Health Administration
United States
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