Role of matrix metalloproteinase-9 in the pathogenesis of osteoporosis in patients with chronic obstructive pulmonary disease

Aim. To determine a relationship between matrix metalloproteinase-9 (MMP-9) activity and its tissue inhibitors TIMP-1 and 2, tumor necrosis factor-α (TNF-α), bone mineral density (BMD), and bone exchange in chronic obstructive pulmonary disease (COPD). Subjects and methods. Seventy-six patients with COPD and 20 healthy volunteers were examined using dual-energy X-ray absorptiometry n the lumbar spine (LII-LIV) and femoral neck (FN). The serum levels of MMP-9, TIMP-1 and TIMP-2, TNF-α, and Β-Crosslaps (ΒCL) were measured. Results. There was a higher MMP-9 level in COPD than that in the controls ((383.8±54.2 and 137.6±31.4 pg/ml, respectively; p<0.01). The levels of TIMP-1 and TIMP-2 were not different from those in the control group. An inverse correlation was found between forced expiratory volume in one second (FEV1) and MMP-9 concentration (r= -0.59; p=0.002) and a positive correlation with smoking index (r=0.47; p=0.04). There was an inverse correlation between MMP-9 concentration and BMD in both LII-LIV and FN (r= -0.67; p<0.001 and r= -0.61; p<0.01, respectively) and a direct correlation with ΒCL (r=0.53; p=0.04). An inverse correlation was established between TNF-α and T index in both LII-LIV (r =-0.54; p<0.01) and FN (r= -0.48; p<0.01). At the same time, the level of TNF-α directly correlated with the bone resorption marker ΒCL (r=0.53; p=0.002) and MMP-9 (r=0.57; p=0.003). Conclusion. Elevated MMP-9 levels may play an important role in type I collagen degradation, giving rise to enhanced bone resorption in COPD.

metalloproteinases, tissue inhibitors of metalloproteinase, osteoporosis, tumor necrosis factor-α, chronic obstructive pulmonary disease