Dextran sodium sulfate-induced colitis causes rapid bone loss in mice.
BACKGROUND
Osteopenia is a common complication of human inflammatory bowel disease (IBD). We evaluated the contribution of colonic inflammation to osteopenia and its mechanism in a murine colitis model.


METHODS
Colitis was induced by adding dextran sodium sulfate (DSS) to the drinking water for 2 weeks to nine-week-old Balb/C male mice. 5% DSS was added on the first week and was reduced to 2.5% on the second week. Age- and sex-matched Balb/C mice served as the control group. Indices of femoral bone mass and architecture were determined by micro computed tomography (muCT). Bone formation parameters and osteoclast number were determined by dynamic histomorphometry. The degree of colonic inflammation was assessed by a clinical disease activity index, and colonic mucosal myeloperoxidase activity.


RESULTS
DSS-treated mice exhibited a significantly lower bone mass compared to controls as indicated by decreased trabecular bone volume (BV/TV) of 32%. This reduction was accompanied by decreased trabecular number (23%) and connectivity density (37%) compared to the controls. No changes were observed in cortical bone indices. Osteopenia resulted from suppressed bone formation, as indicated by decreased trabecular double-labeled surface (dL%) of 90%, mineralizing surface (MS) of 62%, and bone formation rate (BFR) of 67%, and increased bone resorption as indicated by a 34% increase in osteoclast number in DSS-treated mice compared to the controls. Myeloperoxidase activity inversely correlated with trabecular BV/TV (r=-0.67, p=0.02), trabecular number (r=-0.86, p=0.0008) and connectivity density (r=-0.63, p=0.03). Myeloperoxidase activity inversely correlated with the bone formation indices: dL%, MS, and BFR (r=-0.79, p=0.007, r=-0.84, p=0.002, r=-0.83, p=0.003, respectively).


CONCLUSIONS
DSS-induced colitis is associated with reduced femoral bone mass and altered micro architecture, which results from suppressed bone formation and increased bone resorption. The decrease in indices of bone mass, structure and formation are directly linked to the degree of colonic mucosal inflammation. DSS-induced colitis can be used to study pharmacological interventions for bone loss in colitis.
Hamdani
Gilad
G
Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
Gabet
Yankel
Y
Rachmilewitz
Daniel
D
Karmeli
Fanny
F
Bab
Itai
I
Dresner-Pollak
Rivka
R
D000818:Animals; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014057:Tomography, X-Ray Computed
D016264:Dextran Sulfate