Disturbance of the OPG/RANK/RANKL pathway and systemic inflammation in COPD patients with emphysema and osteoporosis

Abstract

BackgroundOsteoporosis is one of the systemic features of COPD. A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear. Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema. The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis. Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.MethodsEighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires. Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA). Twenty age-matched healthy volunteers were recruited as controls.ResultsAmong these eighty patients, thirty-six had normal BMD and forty-four had low BMD. Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05). The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001). Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables. The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance. The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05). The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.ConclusionsRadiographic emphysema is correlated with low BMD in current and former smokers with COPD. IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD.

Air Pollution Exposure and Osteoporosis among Retired Workers with Chronic Obstructive Pulmonary Disease

“…Second, we cannot rule out the possibility of unmeasured confounders even though we have adjusted for several individual-level confounders. Third, the present study did not measure markers that are related to bone metabolism, such as osteocalcin [30] and pro-inflammatory cytokines [31]. Such markers should be analyzed in the future to understand the possible mechanisms underlying the association with NO 2 .…”

The Impact of Emphysema on Chronic Obstructive Pulmonary Diseases

“…Bon et al 27 confirmed that the degree of emphysema in COPD patients is the most important factor associated with the presence of osteoporosis independently of other predictors such as age, gender, tobacco smoking and BMI. Several pathways have been proposed in trying to explain the association of these two matrix degradation processes at different locations of COPD patients, but more research is still needed to try to elucidate the nexus 28 .…”

The clinical relevance of the emphysema-hyperinflated phenotype in COPD

“…Finally, there is increasing data supporting the association of COPD and osteoporosis. The causative mechanisms underlying this association are still being investigated, but are likely modulated by gender, clinical phenotype (with a significant relationship to the severity of emphysema) and genetic predisposition [82][83][84][85].…”