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P044. OPG circulating levels are reduced by infliximab treatment and correlate to CRP levels

L. Pastorelli1,2, E. Galliera3, G. Dogliotti3, C. De Salvo4, G. Tosetti5, G. Banfi6, M.M. Corsi3, M. Vecchi1,2

1Department of Surgical and Medical Sciences, University of Milan, Milan, Italy; 2Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; 3Department of Human Morphology and Biomedical Sciences, University of Milan, Milan, Italy; 4Department of Pathology, Case Western Reserve University, Cleveland, OH, United States; 5Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, Milan, Italy; 6Laboratory of Cell Cultures and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy

Aim: Osteoporosis has a high prevalence among Inflammatory bowel disease (IBD) patients, due to the prolonged and repeated exposure to corticostisteroids, and also because of the direct bone resorptive effect of pro-inflammatory cytokines. The bone metabolism and remodeling are regulated by several molecules, among which, Receptor Activator of NF-kB (RANK), its ligand, RANKL, and Osteoprotegerin (OPG) play a major role. RANKL, upon the binding of its receptor, RANK, a member of the TNF receptor superfamily, potently activates osteoclastogenesis. OPG is a decoy receptor, which binds to RANKL functionally blocking its activity. Anti-TNF therapy, potently decreasing the production of pro-inflammatory cytokines, may modulate the RANK/RANKL/OPG system. Aim of the present study is to evaluate the effects of Infliximab administration on OPG and RANKL serum concentration in patients affected by IBD.

Materials and Methods: Serum OPG and RANKL concentrations were measured in 108 sera collected from 11 IBD patients (6 CD and 5 ulcerative colitis (UC)), before and 2 hours after every IFX infusion (5 mg/kg/infusion), performed from time 0 (T0) to week 22 (W22), according to the usual therapeutic protocol (T0, W2, W6, W14 and W22). Correlation between OPG and RANKL concentrations to C-reactive protein (CRP) levels and to clinical activity was also tested. OPG, RANKL and CRP levels were determined by means of commercially available ELISA kits, whereas clinical activity was assessed using the CDAI for CD and the CAI for UC. Statistical analysis was performed by means of paired Student's t test and linear regression analysis, as appropriate.

Results: 2 hours after IFX infusion, OPG was not acutely modified, but, interestingly, RANKL levels were significantly increased (3.34±0.41 vs. 6.17±0.89 pg/ml, Pre-Infusion and Post-Infusion values respectively; P < 0.005); instead, OPG levels significantly decreased throughout the duration of the IFX therapy (2007.27±336.08 vs. 1631.02±287.00 pg/ml, T0 and W22, respectively; P < 0.01); no significant difference was seen for RANKL values. Mean CRP values, CDAI and CAI scores progressively decreased throughout the study. OPG reflected disease biochemical activity, significantly correlating to CRP serum concentrations (P < 0.05, r = 0.35).

Conclusions: Taken together, our data suggest that the modifications of bone metabolism markers in the serum of IBD patients during Infliximab treatment might not reflect the actual bone turn over, being instead influenced by inflammation itself. In fact, high OPG levels correlate with increased biochemical inflammatory activity in IBD, and may have the potential to be tested in clinical settings as a novel biomarker of intestinal inflammation.