title: Role of Osteoprotegerin and Receptor Activator of Nuclear Factor-κB Ligand in Bone Loss Related to Advanced Chronic Obstructive Pulmonary Disease.
abstract: 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-κB 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-μ) with bone turnover in men with very severe COPD.
  
  
  METHODS
  Pulmonary function, 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 β-CrossLaps (βCL) 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 βCL, TNF-μ, and its receptors were higher. OPG directly correlated with forced expiratory volume in 1 s (FEV1) % 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 βCL (r = 0.48, P < 0.001). In addition, OPG was inversely correlated with RANKL (r = -0.39, P < 0.01), TNF-μ (r = -0.56, P < 0.001), and sTNFR-I (r = -0.40, P < 0.01).
  
  
  CONCLUSIONS
  Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD.
authors.affiliation: Departement of Pulmonology, Central Scientific Research Laboratory, Pacific State Medical University, Vladivostok 690950, Russian Federation.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Ugay
authors.affiliation: Departement of Pulmonology, Central Scientific Research Laboratory, Pacific State Medical University, Vladivostok 690950, Russian Federation.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Kochetkova
authors.affiliation: Departement of Pulmonology, Central Scientific Research Laboratory, Pacific State Medical University, Vladivostok 690950, Russian Federation.
authors.forename: Vera
authors.initials: V
authors.lastname: Nevzorova
authors.affiliation: Departement of Pulmonology, Central Scientific Research Laboratory, Pacific State Medical University, Vladivostok 690950, Russian Federation.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Maistrovskaia
mesh_terms: D015519:Bone Density / Q000502:physiology; D003430:Cross-Sectional Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D053245:RANK Ligand / Q000378:metabolism*; D012129:Respiratory Function Tests; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha