ALTERATIONS IN BONE METABOLISM IN CHILDREN WITH INFLAMMATORY BOWEL-DISEASE - AN IN-VITRO STUDY

Background: In patients with inflammatory bowel disease (IBD), acceler ated bone loss and osteopenia have been found. Potential etiologies of these bone abnormalities have included malnutrition, poor calcium int ake or absorption, and the use of corticosteroids. Recent studies have suggested that circulating pro-inflammatory cytokines, which are prod uced in inflamed bowel, can have a profound effect on bone metabolism, particularly bone resorption. Our aim was to characterize the effects of serum from subjects with IBD on bone metabolism in an in vitro bon e culture system. Methods: Organ cultures of fetal rat parietal bones were treated with sera from 9 subjects with Crohn's disease, 7 with ul cerative colitis, and 10 controls with functional bowel disease (age r ange of all subjects 7-16 years). Patients were also classified by dis ease activity, serum albumin level, erythrocyte sedimentation rate (ES R), and serum interleukin (IL) 6 levels. The effects of sera on bone f ormation and resorption were quantified. Results: Compared with contro l serum, serum from patients with Crohn's disease significantly decrea sed bone dry weight (p < 0.01) and calcium content (p < 0.001) during 96 h of culture, while serum from ulcerative colitis patients had no e ffect. While no difference in collagen synthesis was noted between any of the three experimental groups, noncollagen protein synthesis was l ower in the ulcerative colitis group than in the control group or thos e with Crohn's disease (p < 0.05). DNA content was similar in all grou ps. There was no significant effect of serum from any experimental gro up on bone resorption. There was no demonstrable relationship between clinical disease activity, ESR, or serum IL-6 levels and measures of b one metabolism Histologic evaluation of cultured bone showed marked di fferences between control subjects and Crohn's disease patients, with the latter being characterized by disorganization of mineral and osteo id and morphologically abnormal osteoblasts. Conclusions: Serum from c hildren with IBD has a significantly different effect than control ser um on an in vitro model of bone metabolism. Our data suggest that circ ulating factors may affect osteoblasts and bone formation, leading to bone loss. Further work will be required to further characterize the n ature of these factors and develop treatment strategies to minimize th eir effects. (C) 1997 Lippincott-Raven Publishers.