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Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis

Sylvester, Francisco A. MD1,2; Turner, Dan MD, PhD3,4; Draghi, Andrew II, PhD1; Uuosoe, Krista RN4; McLernon, Robin RN4; Koproske, Kristen BSc1; Mack, David R. MD5; Crandall, Wallace V. MD6; Hyams, Jeffrey S. MD1,2; LeLeiko, Neal S. MD, PhD7; Griffiths, Anne M. MD4

doi: 10.1002/ibd.21561
Original Clinical Articles

Background: Osteoprotegerin (OPG) is increased in inflamed colonic mucosa and has a role in immune regulation and apoptosis resistance. Fecal OPG may be useful in predicting corticosteroid resistance in hospitalized children with severe ulcerative colitis (UC). We aimed to determine whether fecal OPG predicts the need for second-line therapies in children hospitalized for UC.

Methods: We included 83 children with UC admitted for intravenous corticosteroid treatment. Children were classified as responders/nonresponders based on the need for therapy escalation. Fecal OPG results were compared with those of four other fecal markers.

Results: Of the enrolled children, seven had day 1 samples only, 53 children had day 3 samples only, and 23 had both. Twenty-two children failed corticosteroid therapy and required infliximab (n = 20) or colectomy (n = 2). On the third treatment day the median fecal OPG levels were significantly higher in the nonresponders group compared with the responders: 77 pmol/L (interquartile range [IQR] 27–137) versus 13 pmol/L (3–109); P = 0.007. The best day 3 fecal OPG cutoff to predict second-line therapy was >50 pmol/L with a sensitivity of 71% and specificity of 69% (area under the receiver operator curve [ROC] of 0.70%–95% confidence interval [CI] 0.57–0.82). Fecal OPG was superior to day 3 fecal calprotectin, lactoferrin, and S100A12 as a predictor of corticosteroid nonresponse, but equivalent to the less commonly used M2-pyruvate kinase.

Conclusions: Day 3 fecal OPG may guide the decision to institute second-line therapy in children with severe UC. The role of OPG in the inflammatory response in pediatric UC deserves further study. (Inflamm Bowel Dis 2010;)

1Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut, University of Connecticut School of Medicine, Storrs, Connecticut, USA

2Saint Francis Hospital and Medical Center, Department of Research, Hartford, Connecticut, USA

3Shaare Zedek Medical Center, Jerusalem, Israel

4The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

5Children's Hospital of Eastern Ontario, Ottawa, Canada

6Nationwide Children's Hospital, Columbus, Ohio, USA

7Hasbro Children's Hospital, Providence, Rhode Island

Reprints: Francisco A. Sylvester, MD, Division of Digestive Diseases, Hepatology & Nutrition, Connecticut Children's Medical Center, 282 Washington St., Hartford, CT 06106.


Received 14 September 2010; Accepted 5 October 2010

Published online 3 December 2010 in Wiley Online Library (

Grant sponsor: Schering Canada; Grant sponsor: Connecticut Children's Medical Center and a Donaghue Foundation Investigator Award.

The multicenter study, in which stool samples were collected, was partially funded by Schering Canada in an investigator-initiated grant (to A.M.G.). Connecticut Children's Medical Center and a Donaghue Foundation Investigator Award funded the laboratory portion of this work (to F.A.S.).

The first two authors contributed equally to this work.

© Crohn's & Colitis Foundation of America, Inc.
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