engleski

Proinflammatory cytokines and receptor activator of nuclear factor kappaB-ligand/osteoprotegerin associated with bone deterioration in patients with Crohn´s disease

Objectives. The high incidence of bone disease and the increasing evidence for Crohn´s disease (CD) bone decline in corticosteroid users and non-users suggest that bone metabolism is affected by inflammatory process. The aim of the study was to compare serum levels of proinflammatory cytokines, markers of bone turnover and regulatory molecules of osteoclast biogenesis, RANKL and osteoprotegerin (OPG), between naï ; ; ; ; ve and long-standing CD patients. Methods. The study included 95 CD patients, 15 of them with newly diagnosed and previously untreated CD. The spine and hip bone mineral density (BMD) was measured by DXA. Biochemical markers were determined by immunoassay. Results. Reduced BMD (T-score ≤ -1SD) was recorded at diagnosis in 53% of naï ; ; ; ; ve patients and osteoporosis was found in 26% of long-standing CD patients. The newly diagnosed patients showed correlation between TNF-α and sRANKL (r=0.5 ; p=0.04), and this positive relationship characterized the study population as a whole (r=0.3 ; p=0.003). Analysis of the OPG and sRANKL relationship showed absence of correlation in patients with healthy skeleton, while an inverse correlation was found in those with osteopenia (r=-0.31 ; p=0.033) and osteoporosis (r=-0.48 ; p=0.028). In naï ; ; ; ; ve patients with reduced T-score, the correlation between sRANKL and OPG was highly inverse (r=-0.8 ; p=0.02) and these patients were characterized by lower BMI, significantly higher level of proinflammatory cytokines, elevated CRP and increased activity of free sRANKL and OPG. Conclusions. Bone disease that accompanies CD at diagnosis suggests that bone metabolism is affected by the underlying inflammatory process per se, as probably confirmed by our finding of the central proinflammatory cytokine TNF-α being strongly associated with the osteoclastogenic mediator RANKL, and inversely with bone density. .

Crohn's disease; Metabolic bone disease; Osteoprotegerin

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