Naslov
Receptor activator of nuclear factor κ B-ligand, its decoy receptor osteoprotegerin and proinflammatory cytokines associated bone decline in patients with inflammatory bowel disease

Autori
Turk, Nikša ; Čuković-Čavka, Silvija ; Koršić, Mirko ; Turk, Zdenka ; Vucelić, Boris

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Clinical Chemistry and Laboratory Medicine (suppl 1) / - , 2008, S385-S385

Skup
IFCC-WordLab Congress

Mjesto i datum
Fortaleza, Brazil, 28.09.2008. - 02.10.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Inflammatory bowel diseases (IBD); Receptor activator of nuclear factor κ B-ligand (RANKL); Osteoprotegerin

Sažetak
Background/Aim Inflammatory bowel diseases (IBD) are associated with a number of extraintestinal manifestations including low bone mass. As the biogenesis of RANKL/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. To test the hypothesis, it was necessary to evaluate serum concentrations of RANKL and OPG in naï ; ve and long-standing patients, and to correlate these values with proinflammatory cytokines, biochemical markers of bone turnover and bone mineral density (BMD). Patients and Methods The study population included 95 patients, 15 of them newly diagnosed and previously untreated. Serum concentrations of free soluble RANKL, OPG, TNF-α , IL-1β , IL-6, osteocalcin and C-telopeptide cross-linked collagen type I were measured by immunoassays. Reference ranges were derived from 30 age-matched healthy controls. BMD of the spine (L1-L4) and total hip was measured by dual-energy x-ray absorptiometry (DXA). Results Reduced BMD (Z-score ≤ -1SD) was recorded at diagnosis in 40% of naï ; ve patients and BMD below the range for age (Z-score ≤ -2SD) in 37% of long-standing IBD 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 (r=-0.42 ; p=0.033) was found in those with Z-score <-2SD. In naï ; ve patients, the correlation between sRANKL and OPG was highly inverse (r=-0.8 ; p=0.02) and the patients with reduced Z-score were characterized by lower BMI (p=0.025), a significantly higher level of TNF-α (p=0.043) and IL-6 (p=0.028), elevated CRP, and increased activity of free sRANKL (15.8± ; 7 vs 9.3± ; 6 pg/ml ; p=0.033) and OPG (111± ; 60 vs 96± ; 23 pg/ml ; p=0.004). In the group of naϊ ve IBD patients there was a highly negative relationship between humoral TNF-α and BMD Z-scores either at the spine (r=-0.6, p=0.023) or hip (r=-0.63, p=0.015). Conclusion Bone disease that accompanies IBD 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.

Izvorni jezik
Engleski

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