Role of Osteoprotegerin and Receptor Activator of Nuclear Factor-κB Ligand in Bone Loss Related to Advanced Chronic Obstructive Pulmonary Disease

Background: Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-alpha) with bone turnover in men with very severe COPD. Methods: Pulmonary fimction, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-I and II (sTNFR-I, sTNFR-II), osteocalcin (OC), and j-CrossLaps (beta CL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using an independent t-test and Mann-Whitney U-test. The Pearson coefficient was used to assess the relationships between variables. Results: OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum beta CL, TNF-alpha, and its receptors were higher. OPG directly correlated with forced expiratory volume in 1 s (FEVl) % predicted (r = 0.46, P < 0.005), OC (r = 0.34, P < 0.05), LS (r = 0.56, P < 0.001), and FN T-score (r = 0.47, P < 0.01). In contrast, serum RANKL inversely associated with LS and FN T-score (r = -0.62, P < 0.001 and r = -0.48, P< 0.001) but directly correlated with 3CL (r = 0.48, P < 0.001). In addition, OPG was inversely correlated with RANKL (r = -0.39, P < 0.01), TNF-(r = -0.56, P < 0.001), and sTNFR-I (r = -0.40, P < 0.01). Conclusion: Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD.