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Soluble RANKL/Osteoprotegerin relationship to bone status in patients with inflammatory bowel disease

INTRODUCTION: Inflammatory bowel disease (IBD) is frequently associated with bone disease and increased risk of fragile fractures. We hypothesised that low bone mineral density (BMD) in patients with IBD might be mediated through the osteoclastogenic factor RANKL (the ligand for receptor activator of NFκ B), produced by an exaggerated activity of T ­lymphocytes. We further hypothesised that imbalance in RANKL/osteoprotegerin (osteoclastogenesis inhibitory factor) regulation system might favour increased bone resorption. AIMS & METHODS: In this report we evaluated soluble-RANKL (in free and OPG-complexed form) and osteoprotegerin level in peripheral blood of IBD patients compared to controls, as well as the association with bone status. Thirty-four patients with different stages of IBD (Crohn's disease n = 22, ulcerative colitis n = 11, Intermediate sy n = 1 ; median age 33 years, range 18– 63) and 20 healthy controls were recruited. Bone status was evaluated at the time of study in all patients using calcaneal quantitative ultrasonography (QUS) and dual X­ray absorptiometry (DXA). Immunoassay was performed to estimate sRANKL and OPG levels. RESULTS: Free soluble RANKL was detectable in 70% of patients whereas in the controls only 30% was positive. Serum OPG was significantly higher in IBD-patients in comparison to healthy controls (85.8±31 vs 52±16 pg/ml ; p = 0.000018). Patients with t­scores indicating osteopenia and osteoporosis showed significantly higher concentrations of OPG than controls or patients with normal t­scores (p<0.0002). OPG level was significantly but inversely associated with calcaneal QUS parameters BUA (r = -0.5, p = 0.00025) and SOS (r = -0.51, p = 0.000016). As well as, there was negative correlation with bone mineral density (BMD) of lumbal spine (r = -0.54, p = 0.015) and total hip (r = -0.55, p = 0.0014) measured by DXA. CONCLUSION: The results of this pilot study revealed significant differences in the levels of osteoprotegerin and free sRANKL in peripheral blood of IBD patients when compared with healthy controls. Significantly higher osteoprotegerin in IBD patients with osteopenia and osteoporosis could reflect a compensatory response to increased bone resorption process.

Crohn disease; ulcerative colitis; metabolic bone disease

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