P258 BIOMARKERS OF INFLAMMATION AND BONE TURNOVER ASSOCIATED BONE LOSS IN NAïVE AND LONG-STANDING PATIENTS WITH CROHN'S DISEASE

Abstract

Background/Aim The high incidence of bone disease and the increasing evidence that Crohn´s disease (CD) affects bone status in corticosteroid users and non-users suggest that bone metabolism is affected by the underlying inflammatory process. As the biogenesis of receptor activator of nuclear factor κ B-ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) may be a consequence of intestinal inflammation and because this signal pathway is shared between the immune and bone system, we hypothesized that the action of sRANKL, OPG and other inflammatory cytokines is not limited to the induction of local inflammation but might be directly or indirectly involved in the activation of bone metabolism. The aim of this study was to determine comparative serum levels of proinflammatory cytokines, markers of bone formation and resorption, and regulatory molecules of osteoclast biogenesis in CD patients with and without established metabolic bone disease. Patients and Methods The study population included 95 patients, 15 of them newly diagnosed and untreated. Serum concentrations of free soluble RANKL, OPG, TNF-α , IL-1β , IL-6, osteocalcin and C-telopeptide type I were measured by immunoassay. Reference ranges were derived from 30 age-matched healthy controls. Bone mineral density (BMD) of the spine and total hip was measured by DXA. Results We found 53% of Crohn´s patients with reduced BMD (t-score≤ 1.0) at diagnosis, and low bone mass in 72% of the study population. Elevated concentrations of sRANKL, OPG, TNF-α and IL-6 were found in patients with bone disease (p<0.01). In the newly diagnosed, previously untreated patients there was a good association between TNF-α and free sRANKL (r=0.6 ; p=0.027), and this positive correlation remained unchanged in the unselected study population as a whole (r=0.5 ; p=0.002). Stepwise multiple regression indicated TNF-α to be the best predictor of sRANKL (p<0.001). Patients with increased parameter of bone resorption were characterized by elevation of TNF-α , IL-6, CRP and OPG in systemic circulation. Analysis of the OPG and sRANKL relationship according to subgroups showed absence of correlation in patients with healthy skeleton, and an inverse relationship in those with pathologic BMD (r=-0.36 ; p=0.003). In the newly diagnosed patients with reduced BMD, correlation between free sRANKL and OPG was highly inverse (r=-0.8 ; p=0.02), whereas in those with normal BMD there was no relationship. Conclusion We found low bone mass in 50% of newly diagnosed and untreated Crohn´s patients. In nai ; ; ; ve Crohn´s patients we demonstrated strong relationship between TNF-α and the osteoclastic mediator sRANKL, and this positive correlation persisted across the unselected study population. Free sRANKL and OPG showed highly inverse relationship in patients with pathological bone density but not in those with healthy skeleton. Data on the newly diagnosed patients support the prominent role of inflammation in bone loss. Therefore, bone disease that accompanies Crohn´s disease needs to be considered for therapeutic options already at the diagnosis