Identification of mechanisms and biomarkers of bone loss in patients with Cystic Fibrosis

Abstract

Background: Cystic Fibrosis (CF) Bone Disease (CFBD), accompanied by bone mass reduction, is a common but not well-understood complication in adult patients, with devastating consequences to their quality of life and longevity. Amongst the possible etiologies for CFBD, recurrent infective exacerbations correlate with increased bone degradation. We previously found in the murine model that soluble bone catabolic mediators, such as Serum Amyloid A (SAA), increase in response to infection. Therefore, we hypothesize that sustained inflammatory status induced by chronic infections substantially contributes to decreased bone mass. Here, we aimed to understand whether SAA or other immune mediators may be used as novel biomarkers to monitor bone mass in CF patients. Methods: This was a transversal observational study at a single CF care center consisting of twenty-six adult CF patients. Circulating levels of several bone turnover biomarkers, cytokines and chemokines were measured in the plasma and correlated with bone mineral density (BMD). Results: We found that SAA were increased in CF patients with normal and low BMD and did not correlate with BMD in lumbar spine and femur. Circulating SAA levels in CF patients positively correlated with pulmonary function (as measured by the percentage of predicted forced expiratory volume, %FEV1). On the other hand, BMD positively correlated with %FEV1 and IL1 and negatively with osteoprotegerin and immune mediators such as MCP-3, M-CSF, TNF. Conclusions: This pilot study showed that the persistent inflammatory status of CF patients correlates with decreased bone mass. Furthermore, we identified potential candidates to monitor bone loss in these patients, laying the ground for future investigations on the mechanisms that modulate the impact of these immune mediators on bone metabolism.