title: Are activated T cells regulators of bone metabolism in children with Crohn disease?
abstract: OBJECTIVE
  To test the hypothesis that circulating activated T cells may release cytokines that decrease bone turnover in children with Crohn disease.
  
  
  METHODS
  Newly diagnosed Crohn disease and healthy controls of similar age were compared for bone age, bone mineral content and density, markers of bone remodeling, and serum concentration and in vitro T-cell production of receptor activator of nuclear factor kappaB ligand (RANKL), interferon (INF)-gamma, and osteoprotegerin (OPG).
  
  
  RESULTS
  Newly diagnosed children with Crohn disease (n=23) had similar bone mineral density (BMD) z-scores and body mass index as the controls (n=40). Biochemical markers of bone remodeling indicated a state of low bone turnover in the Crohn disease patients compared with controls. Serum OPG (pmol/L; mean+/-SD, median) was higher (4.24+/-1.74, 3.98 vs 3.38+/-0.83, 3.41; P<.05), and serum RANKL (pmol/L) was lower in the Crohn disease patients (0.50+/-0.86, 0.28 vs 1.02+/-1.63, 0.49; P<.01), consistent with decreased bone resorption. Activated T cells from Crohn disease patients produced a higher concentration of INF-gamma (ng/microg protein) than those from controls (20.03+/-26.39, 8.70 vs 9.76+/-14.10, 6.17; P<.05).
  
  
  CONCLUSIONS
  The newly diagnosed children with Crohn disease exhibited reduced bone remodeling, possibly due to T-cell INF-gamma and OPG.
authors.affiliation: Connecticut Children's Medical Center, Saint Francis Hospital & Medical Center, Hartford 06106, and University of Connecticut School of Medicine, Farmington, Connecticut, USA. fsylves@ccmckids.org
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Sylvester
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Davis
authors.forename: Nancy
authors.initials: N
authors.lastname: Wyzga
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hyams
authors.forename: Trudy
authors.initials: T
authors.lastname: Lerer
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D015519:Bone Density / Q000276:immunology; D016723:Bone Remodeling / Q000276:immunology; D001862:Bone Resorption / Q000209:etiology / Q000276:immunology*; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D003424:Crohn Disease / Q000150:complications / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016015:Logistic Models; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D007371:Interferon-gamma