Relationship between bone resorption, oxidative stress and inflammation in severe COPD exacerbation

Abstract

Background: The natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and co-morbidities. Increasing evidence indicates that COPD and osteoporosis are strongly linked. The common features in COPD pathology, history of smoking, age, inactivity, systemic inflammation, and use of systemic corticosteroids, are important risk factors for osteoporosis. Methods: Pulmonary function, matrix metalloproteinase, tissue inhibitor of metalloproteinases, oxidative stress parameters, inflammatory markers and bone resorption marker were measured in 85 COPD patients and 47 healthy subjects. In patients, all parameters were assessed at two time points: one day after admission during exacerbation and about 30 days after, in the stable state of disease. Results: In patients, bone resorption marker collagen type I p-isomerized C-terminal telopeptide (beta CL) was increased during exacerbation: geometric mean 0.521, compared with stable patients 0.408, p lt 0.01, and control subjects 0.362 ng/ml, p lt 0.001. During exacerbation high sensitivity C-reactive protein (hsCRP) and neutrophil count were significantly higher in COPD patients compared with the control group, p lt 0.001. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations were significantly higher in COPD patients, stable state or exacerbation, compared with control subjects, p lt 0.001. In patients during exacerbation, total oxidative status (TOS) was higher compared with the stable state, p lt 0.05 and control group, p lt 0.001. Multiple linear regression for the joint influence of inflammation, hypoxia and oxidative status during exacerbation showed almost 60% influence on the variability of beta CL concentrations. Conclusion: Intensification of disease characteristic symptoms such as inflammation, hypoxia, protease/antiprotease imbalance and oxidative stress, during exacerbation episodes in COPD patients may also contribute to increased bone resorption.