Aim: To assess the relationships of serum osteoprotegerin (OPG), receptor-activator of nuclear factor-κB ligand (RANKL) and tumor necrosis factor-alpha (TNF-α) superfamily with bone composition in end-stage COPD.
Methods: Body and bone composition, serum OPG, RANKL, TNF-α and its receptors (sTNFR I, sTNFR II), TNF-related apoptosis-inducing ligand (sTRAIL) levels were measured in 48 men end-stage COPD accepted for lung transplantation, and 36 male non COPD volunteers.
Results: OPG was lower in male COPD patients than in control whereas RANKL, TNF-α and its receptors were higher. No notably difference in the serum sTRAIL concentrations between the two groups. OPG directly correlated with FEV1% (r=0.49, P=0.0005), fat mass index (r=0.46, P=0.001), lumbar and femoral T-score (r=0.653, P<0.0001 and r=0.686, P<0.0001). Serum RANKL inversely associated with FEV% (r=0.49, P=0.0004), body lean mass (r=−0.68, P<0.0001), lumbar and femoral T-score (r=−0.65, P<0.0001 and r=−0.56, P<0.0001) but directly correlated with TNF-a (r=0.52, P=0.0002). A similar pattern of association with FEV1 was observed for sTRAIL, TNF-α and its receptors. OPG was inversely correlated with RANKL (r=−0.56, P<0.0001), TNF-a (r=−0.62, P<0,0001), sTRAIL (r=−0.31, P=0.034) and sTNFR-I (r=−0.512, P<0.0001). Using backward selection multivariable regression, increased serum TNF-α and RANKL were independently associated with lumbar bone loss (adjusted R2=0.61) while RANKL and weight independently predicted femoral T-score (adjusted R2=0.564). In addition, an increased level of serum RANKL and lowered serum OPG concentration were independently associated with reduced skeletal lean mass (adjusted R2=0.51).
Conclusion: Our results suggest that serum RANKL levels are remained significantly associated with reduced pretransplant BMD in male COPD.
Acknowledgments: This study was supported by grants from Russian Science Foundation (No. 14-33-00009).
Keywords: osteoporosis, chronic obstructive pulmonary disease, TNF-α, osteoprotegerin, RANKL, bone metabolism
14 May 2016 - 17 May 2016