Js. Hyams et al., ALTERATIONS IN BONE METABOLISM IN CHILDREN WITH INFLAMMATORY BOWEL-DISEASE - AN IN-VITRO STUDY, Journal of pediatric gastroenterology and nutrition, 24(3), 1997, pp. 289-295
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.