Exacerbations key to COPD–osteoporosis connection
medwireNews: Researchers have shown that bone resorption is increased during exacerbations of chronic obstructive pulmonary disease (COPD), adding to growing evidence of a strong association between the disease and osteoporosis.
Furthermore, they demonstrate that this change in bone mineral dynamics was predominantly influenced by the inflammation, hypoxia, and increased oxidative stress brought about by acute respiratory exacerbation.
The study of 85 hospitalized COPD patients showed that during exacerbation mean levels of the bone resorption marker collagen type 1 ß-isomerized C-terminal telopeptide (beta CL) were significantly greater than during stable disease (approximately 30 days following admission) at 0.521 ng/mL compared with 0.408 ng/mL. But both of these levels were significantly higher than that observed among a group of 47 controls, at a mean of 0.362 ng/mL.
The change in bone resorption rate observed in acute COPD exacerbations was accompanied by expected declines in respiratory function and the development of significant hypoxia. And while inflammation was persistent in the stable state, it was intensified during exacerbations, as evidenced by increased neutrophil counts and high-sensitivity C-reactive protein levels.
Additionally, total oxidative status was higher in COPD patients than controls, a difference that became highly significant during exacerbations (15.9 vs 10.1 mmol/L).
Using multiple linear regression analysis, the authors found that inflammation explained around 18% of variability in beta CL values, while hypoxia and inflammation together explained around 25%. However, it was the combination of inflammation, hypoxia, and oxidative status that could best account for the changes in beta CL, being responsible for 60% of variability, “which firmly established a connection between inflammation, respiratory dysfunction and oxidative stress status,” say study author Ivana Stanojkovic (University of Belgrade, Serbia) and colleagues.
The team also notes that levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 were significantly higher among COPD patients, during both exacerbation and in the stable state. And a slight increase in the former and decrease in the latter during exacerbation resulted in a significantly raised MMP-9 to TIMP-1 ratio, supporting the theory of unbalanced protease activity in COPD, leading to preferential loss of protein rich tissues such as skeletal muscle and bone connective tissue.
“Results of this analysis have confirmed the strong relationship between proteolytic and bone resorption processes in patients with jeopardized respiratory function,” the researchers conclude in Clinical Biochemistry.
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By Kirsty Oswald, medwireNews Reporter