Circulating matrix metalloproteinase-9 and osteoporosis in patients with chronic obstructive pulmonary disease.
Matrix metalloproteinase-9 (MMP-9) has been implicated in airways injury in chronic obstructive pulmonary disease (COPD). Osteoporosis is common in patients with COPD, and MMP-9 is an indicator of activated osteoclasts. We hypothesized that circulating MMP-9 would be related to bone mineral density (BMD) in COPD. We explored the relationship between MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1 and -2, and BMD status in patients with COPD. A total of 70 clinically stable patients with confirmed COPD and 39 control subjects underwent spirometry, dual-energy x-ray absorptiometry to determine BMD, and venous sampling for measurement of cytokines and MMP-9 and TIMP-1 and -2. In patients, circulating MMP-9 was increased: mean (SD) 38.5 (2.2) compared with control subjects 20.1 (2.0) ng/mL, P < 0.001, whereas TIMP-1 and -2 were not different. In the patients, MMP-9 was greater in those with osteoporosis, compared with those with osteopenia, no bone disease or control subjects, and patients with osteopenia had greater MMP-9 than control subjects. The adjusted receiver operating characteristics curve area for MMP-9 detecting osteoporosis was 0.86. Patients had elevated systemic inflammatory mediators compared with control subjects, but these were unrelated to bone status. Increased circulating MMP-9 in patients with COPD was related to the presence of osteoporosis and not to lung function. MMP-9 may be a biomarker of increased bone resorption.
Bolton
C E
CE
Department of Respiratory Medicine, School of Medicine, Cardiff University, Academic Centre, University Hospital Llandough, Penlan Road, Penarth. Vale of Glamorgan CF64 2XX. UK. boltonce@cf.ac.uk
Stone
M D
MD
Edwards
P H
PH
Duckers
J M
JM
Evans
W D
WD
Shale
D J
DJ
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D010024:Osteoporosis / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000150:complications* / Q000201:enzymology*; D012372:ROC Curve; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
D015415:Biomarkers; D018836:Inflammation Mediators; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9