title: Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones.
abstract: OBJECTIVE
  Bone loss is a common complication of human inflammatory bowel disease (IBD), but its mechanisms are not understood completely. We investigated bone metabolism in interleukin-10-deficient ( IL-10-/- ) mice, an animal model with IBD features.
  
  
  METHODS
  IL-10-/- male mice (8- and 12-weeks-old) and their age-matched wild-type counterparts (C57BL/6J) were studied. Bone mass of the femur was determined by ashing. Tibial cancellous and cortical bone mass and formation was measured by static and dynamic histomorphometry. Biomechanical strength of the femur was tested. Primary bone marrow stromal cell cultures were used to assess osteoblast generation. Serum levels of 25-OH vitamin D 3, insulin-like growth factor-1 (IGF-1), parathyroid hormone, osteocalcin, and deoxy-pyridinoline cross-links were measured. The presence of colitis was determined histologically, and by IL-12 and interferon-gamma (IFN-gamma) secretion from cultured colonic explants.
  
  
  RESULTS
  Eight- and 12-week-old IL-10-/- mice developed osteopenia of both cancellous and cortical bone, evidenced by lower femoral ash weight, cancellous bone area and surface, trabecular number, and decreased cortical bone area and width. Osteopenia was associated with mechanical fragility, manifested by decreased stiffness and mechanical load at fracture, and was caused by suppressed bone formation, indicated by decreased cancellous double-labeled surface, mineralizing surface, serum osteocalcin level, and mineralized nodule number in bone marrow stromal cell cultures. IL-10-/- mice with colitis had significantly less bone mass compared with IL-10-/- mice without colitis.
  
  
  CONCLUSIONS
  IL-10-/- mice develop the hallmarks of osteoporosis, that is, reduced bone mass, increased mechanical fragility, and suppressed bone formation. The presence of colitis is an important contributor to osteoporosis in IL-10-/- mice.
authors.affiliation: Endocrinology and Metabolism Service, Hadassah University Hospital, P.O. Box 12000, Jerusalem IL-91120, Israel. rivkap@md.huji.ac.il
authors.forename: Rivka
authors.initials: R
authors.lastname: Dresner-Pollak
authors.forename: Nir
authors.initials: N
authors.lastname: Gelb
authors.forename: Daniel
authors.initials: D
authors.lastname: Rachmilewitz
authors.forename: Fanny
authors.initials: F
authors.lastname: Karmeli
authors.forename: Miron
authors.initials: M
authors.lastname: Weinreb
mesh_terms: D000818:Animals; D015519:Bone Density / Q000276:immunology; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000276:immunology; D001842:Bone and Bones / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000276:immunology*; D016753:Interleukin-10 / Q000172:deficiency* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010012:Osteogenesis / Q000276:immunology*; D010024:Osteoporosis / Q000209:etiology / Q000276:immunology*
chemical_list: D016753:Interleukin-10