Experimental colitis impairs linear bone growth independent of nutritional factors.
BACKGROUND
Poor linear growth frequently complicates chronic inflammatory bowel disease in children. Circulating inflammatory mediators may play a role in this growth delay. We evaluated the effect of experimental colitis on bone growth in a nutritionally controlled rat model.


METHODS
Experimental colitis was induced in male Sprague-Dawley rats (125-150 g) by enema with trinitrobenzene sulfonic acid in 50% ethanol on day 1 and 11 of a 14-day protocol. Control animals were pair-fed and all animals received a liquid rat diet (1 kcal/ml). Twenty-four-hour urine, collected on days 2 and 12 and serum samples, collected at death, were analyzed for calcium, zinc, and magnesium. Serum samples from a separate set of animals were studied for serial interleukin-6 levels. Right proximal tibias were processed for growth-plate histomorphometry, in which linear growth is proportional to the heights of the proliferative zone, and terminal hypertrophic chondrocyte, but inversely proportional to the height of the resting zone.


RESULTS
Histology confirmed active inflammation in the animals given trinitrobenzene sulfonic acid. Weight gain and both urinary excretion and serum levels of zinc, calcium, and magnesium did not differ between treatment and nontreatment groups. Histologically, there was impaired linear bone growth. The resting zone was greater in the colitis group (94.5 +/- 32.6 microns versus 3.9 +/- 5.4 microns; p < 0.05); the proliferative zone was smaller in the colitis group (123.7 +/- 18.2 microns versus 78.9 +/- 11.2; p < 0.05 micron); the terminal hypertrophic chondrocyte was reduced in the colitis group (19.5 +/- 1.4 microns versus 28.8 +/- 3.6 microns; p < 0.05). At 6 and 24 hours after induction, the level of interleukin-6 was elevated in the colitis group.


CONCLUSIONS
Experimental colitis results in a decreased linear bone growth, independent of nutritional intake. Circulating cytokines derived from intestinal inflammation may contribute to the suppression of bone growth.
Koniaris
S G
SG
Department of Pediatrics, North Shore University Hospital-New York University School of Medicine, Manhasset, USA.
Fisher
S E
SE
Rubin
C T
CT
Chawla
A
A
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001681:Biological Assay; D001846:Bone Development / Q000502:physiology*; D002118:Calcium / Q000097:blood / Q000652:urine; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology* / Q000652:urine; D003106:Colon / Q000473:pathology; D004195:Disease Models, Animal; D006132:Growth Plate / Q000254:growth & development*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008274:Magnesium / Q000097:blood / Q000652:urine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000254:growth & development; D013997:Time Factors; D015430:Weight Gain / Q000502:physiology; D015032:Zinc / Q000097:blood / Q000652:urine
D015850:Interleukin-6; D008274:Magnesium; D015032:Zinc; D002118:Calcium