Abstract
Cystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation. Endocrine complications, such as CF bone disease (CFBD), are increasingly identified as patients are living longer. The cause of CFBD is multifactorial with chronic systemic inflammation theorized to be a contributing factor. Thus, we attempted to identify inflammatory biomarkers that are associated with CFBD. We conducted a retrospective observational study of 56 adult patients with CF with an average percentage predictive forced expiratory volume in one second (ppFEV1) of 73.7% (standard deviation: 30.0) who underwent baseline serum analysis for osteoprotegerin (OPG) and pro-inflammatory biomarkers (IL-1β, IL-6, IL-8 and TNF-α), and had repeated dual-energy x-ray absorptiometry (DXA) scans separated by at least 2 years to examine correlations between serum biomarkers and bone mineral density (BMD) measurements. Univariate linear regression model analysis demonstrated that serum IL-1β and IL-8, but not other pro-inflammatory markers, were negatively correlated with baseline BMD results. However, after accounting for confounding variables, only the relationship between IL-8 and left femoral neck BMD remained statistically significant. Additionally, IL-8 level was associated with BMD decline over time. These results suggest that IL-8 might play a unique role in the pathophysiology of CFBD relative to other pro-inflammatory cytokines but further study is warranted before firm conclusions can be made.
Highlights
Cystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation
There are likely multiple factors in CF that confers an imbalance between osteoblast and osteoclast activity that may result in CF bone disease (CFBD), including CFTR dysfunction directly impairing new bone formation[9] via reduced osteoblast a ctivity[10], as well as secondary causes, including malabsorption of calcium and vitamin D as a result of pancreatic insufficiency and recurrent pulmonary infections that lead to increased inflammatory bone r esorption[2,4,11,12]
We examined the relationship between clinical characteristics or baseline blood biomarkers with bone density change over time using a multivariate linear mixed effect models, adjusted for age, sex, p pFEV1, body mass index (BMI) and CF-related diabetes (CFRD) (Table 4)
Summary
Cystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation Endocrine complications, such as CF bone disease (CFBD), are increasingly identified as patients are living longer. When human CF osteoblasts were provided with a proinflammatory stimulus, RANK-L production increased markedly while osteoprotegerin (OPG), a competitive inhibitor of RANK-L signalling, was found in relatively lower concentrations than RANK-L and as a result, osteoclastogenesis was favoured[16] It remains unclear how these in vitro findings may impact clinical changes to BMD and CFBD development
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