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Circulating matrix metalloproteinase-9 and osteoporosis in patients with chronic obstructive pulmonary disease

Department of Respiratory Medicine, School of Medicine, Cardiff University, Academic Centre, University Hospital Llandough, Penlan Road, Penarth. Vale of Glamorgan CF64 2XX. UK boltonce{at}cf.ac.uk

MD Stone

Bone Research Unit, School of Medicine, Cardiff University, Academic Centre, Llandough Hospital, Penlan Road, Penarth, Vale of Glamorgan CF64 2XX. UK

PH Edwards

On behalf of Ely Bridge Surgery, Mill Road, Ely, Cardiff, UK

JM Duckers

Department of Respiratory Medicine, School of Medicine, Cardiff University, Academic Centre, University Hospital Llandough, Penlan Road, Penarth. Vale of Glamorgan CF64 2XX. UK

WD Evans

Medical Physics and Clinical Engineering Directorate, University Hospital of Wales, Cardiff CF14 4XW. UK

DJ Shale

Department of Respiratory Medicine, School of Medicine, Cardiff University, Academic Centre, University Hospital Llandough, Penlan Road, Penarth. Vale of Glamorgan CF64 2XX. UK

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.

Key Words: ageing • bone densitometry • COPD • matrix proteins • osteoporosis

Chronic Respiratory Disease, Vol. 6, No. 2, 81-87 (2009)
DOI: 10.1177/1479972309103131


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