title: Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis.
abstract: 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.
authors: Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut, USA. fsylves@ccmckids.org
authors: Francisco A
authors: FA
authors: Sylvester
authors: Dan
authors: D
authors: Turner
authors: Andrew
authors: A
authors: Draghi
authors: Krista
authors: K
authors: Uuosoe
authors: Robin
authors: R
authors: McLernon
authors: Kristen
authors: K
authors: Koproske
authors: David R
authors: DR
authors: Mack
authors: Wallace V
authors: WV
authors: Crandall
authors: Jeffrey S
authors: JS
authors: Hyams
authors: Neal S
authors: NS
authors: Leleiko
authors: Anne M
authors: AM
authors: Griffiths
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D005243:Feces / Q000737:chemistry*; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D053244:Osteoprotegerin / Q000032:analysis* / Q000378:metabolism; D011237:Predictive Value of Tests; D012372:ROC Curve; D012720:Severity of Illness Index; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D053244:Osteoprotegerin