Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice

Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1020-9. doi: 10.1152/ajpgi.90696.2008. Epub 2009 Mar 19.


Decreased bone density and stature can occur in pediatric patients with inflammatory bowel disease (IBD). Little is known about how IBD broadly impacts the skeleton. To evaluate the influence of an acute episode of IBD on growing bone, 4-wk-old mice were administered 5% dextran sodium sulfate (DSS) for 5 days to induce colitis and their recovery was monitored. During active disease and early recovery, trabecular bone mineral density, bone volume, and thickness were decreased. Cortical bone thickness, outer perimeter, and density were also decreased, whereas inner perimeter and marrow area were increased. These changes appear to maintain bone strength since measures of moments of inertia were similar between DSS-treated and control mice. Histological (static and dynamic), serum, and RNA analyses indicate that a decrease in osteoblast maturation and function account for changes in bone density. Unlike some conditions of bone loss, marrow adiposity did not increase. Similar to reports in humans, bone length decreased and correlated with decreases in growth plate thickness and chondrocyte marker expression. During disease recovery, mice experienced a growth spurt that led to their achieving final body weights and bone length, density, and gene expression similar to healthy controls. Increased TNF-alpha and decreased IGF-I serum levels were observed with active disease and returned to normal with recovery. Changes in serum TNF-alpha (increased) and IGF-I (decreased) paralleled changes in bone parameters and returned to normal values with recovery, suggesting a potential role in the skeletal response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adipocytes / metabolism
  • Animals
  • Biomarkers / metabolism
  • Bone Density
  • Bone Remodeling*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism
  • Bone and Bones / physiopathology*
  • Cell Differentiation
  • Chondrocytes / metabolism*
  • Chondrocytes / pathology
  • Colitis / chemically induced
  • Colitis / diagnostic imaging
  • Colitis / metabolism
  • Colitis / physiopathology*
  • Dextran Sulfate
  • Disease Models, Animal
  • Down-Regulation
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology
  • Recovery of Function
  • Time Factors
  • Tomography, X-Ray Computed
  • Tumor Necrosis Factor-alpha / blood


  • Biomarkers
  • Tumor Necrosis Factor-alpha
  • Insulin-Like Growth Factor I
  • Dextran Sulfate