Pathogenesis of osteoporosis in advanced stages chronic obstructive pulmonary disease (COPD) is unclear. Therefore, the study of OPG-RANK-RANKL axis contribution to pathogenesis of osteopenic syndrome in COPD is of particular interest. Aim: to estimate the relationships between serum OPG, RANKL, TNF-α and bone metabolism markers levels, bone mineral density (BMD) in advanced stages COPD. Methods: pulmonary function, BMD at the lumbar spine and femoral neck, serum OPG, RANKL, TNF-α and its receptors (sTNFR I, sTNFR II), osteocalcin (bone formation marker), and βCrossLaps (marker of bone resorption) levels were measured in 67 patients with severe and very severe stages COPD and 82 healthy. Results: 61% COPD patients have osteoporosis and BMD were normal in 12% subjects. Osteopenic syndrome (osteopenia and osteoporosis) was determinated in 44% control individuals. Serum βCrossLaps, TNF-α and its receptors, RANKL levels were significant higher and osteocalcin, OPG concentrations were lower in patients with COPD than in control. The univariate analysis showed that OPG correlated with FEV1 (r=0,63, p<0,001), osteocalcin (r=0,57, p<0,01), both lumbar and femur neck BMD (lumbar: r=0,43, p<0,05 and femur neck: r=0,64, p<0,001), pCO2 (r=-0,39, p<0,05), RANKL (r=-0,67, p<0,001), TNF-a (r=-0,046, p<0,05), and its receptors (sTNFR-I: r=-0,41, p<0,05 and sTNFR-II: r=-0,37, p<0,05). In contrast, we established the inverse relationship between serum RANKL and BMD both at the lumbar spine and at the femur neck (r=-0,48, p<0,01 and r=-0,59, p<0,00 1 respectively); and also direct correlation with βCrossLaps (r=0,42, p<0,05). There were no relationships between serum RANKL levels and pulmonary lung parameters, TNF-α and its receptors. Conclusion: our results suggest that serum OPG and RANKL levels participate in the pathogenesis of respiratory failure and loss of bone density in patients with advanced stages COPD