Interrelationship of Circulating Matrix Metalloproteinase-9, TNF-α, and OPG/RANK/RANKL Systems in COPD Patients with Osteoporosis

Previous studies have shown that matrix metalloproteinase-9 (MMP-9) and its cognate inhibitor TIMP-1, inflammatory cytokine TNF-alpha, and the OPG/RANK/RANKL system may each play individual roles in the pathogenesis of osteoporosis in patients with COPD. In the present study, we investigated the interrelationships of these factors in male COPD patients with and without osteoporosis. The serum levels of MMP-9, MMP-9/TIMP-1 ratio, TNF-alpha, RANKL, OPG, and the RANKL/OPG ratio were higher in COPD patients with osteoporosis than in individuals with normal or low bone mineral density (BMD) (N = 30, all P < 0.05 or < 0.01). The lung function FEV1%Pre and the BMD of the lumbar spine and femoral neck were found to be negatively correlated with MMP-9 serum level (r = -0.36, P < 0.05, r = -0.58, P < 0.001, and r = -0.62, P < 0.01, respectively), RANKL serum level (r = -0.21, P < 0.05, and r = -0.25, P < 0.05, and r = -0.26, P < 0.05, respectively), and RANKL/OPG ratio (r = -0.23, P < 0.05, r = -0.33, P < 0.05, and r = -0.38, P < 0.05, respectively). However, they had no correlation with TIMP-1, TNF-alpha, OPG, or RANK. The MMP-9 serum level was found to be positively correlated with TNF-alpha level (r = 0.35, P < 0.05) and RANKL/OPG ratio (r = 0.27, P < 0.05) but not associated with RANKL. These results suggest that MMP-9, TNF-alpha, and the OPG/RANK/RANKL system may be closely interrelated and may play interactive roles in pathogenesis of osteoporosis in COPD.