Alterations in bone metabolism in children with inflammatory bowel disease: an in vitro study.
BACKGROUND
In patients with inflammatory bowel disease (IBD), accelerated bone loss and osteopenia have been found. Potential etiologies of these bone abnormalities have included malnutrition, poor calcium intake or absorption, and the use of corticosteroids. Recent studies have suggested that circulating pro-inflammatory cytokines, which are produced 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 bone culture system.


METHODS
Organ cultures of fetal rat parietal bones were treated with sera from 9 subjects with Crohn's disease, 7 with ulcerative colitis, and 10 controls with functional bowel disease (age range of all subjects 7-16 years). Patients were also classified by disease activity, serum albumin level, erythrocyte sedimentation rate (ESR), and serum interleukin (IL) 6 levels. The effects of sera on bone formation and resorption were quantified.


RESULTS
Compared with control serum, serum from patients with Crohn's disease significantly decreased 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 effect. While no difference in collagen synthesis was noted between any of the three experimental groups, noncollagen protein synthesis was lower in the ulcerative colitis group than in the control group or those with Crohn's disease (p < 0.05). DNA content was similar in all groups. There was no significant effect of serum from any experimental group on bone resorption. There was no demonstrable relationship between clinical disease activity, ESR, or serum IL-6 levels and measures of bone metabolism. Histologic evaluation of cultured bone showed marked differences between control subjects and Crohn's disease patients, with the latter being characterized by disorganization of mineral and osteoid and morphologically abnormal osteoblasts.


CONCLUSIONS
Serum from children with IBD has a significantly different effect than control serum on an in vitro model of bone metabolism. Our data suggest that circulating factors may affect osteoblasts and bone formation, leading to bone loss. Further work will be required to further characterize the nature of these factors and develop treatment strategies to minimize their effects.
Hyams
J S
JS
Department of Pediatrics, Hartford Hospital, Connecticut, USA.
Wyzga
N
N
Kreutzer
D L
DL
Justinich
C J
CJ
Gronowicz
G A
GA
D000293:Adolescent; D000818:Animals; D001799:Blood Sedimentation; D001862:Bone Resorption; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism*; D002648:Child; D003093:Colitis, Ulcerative / Q000097:blood / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009924:Organ Culture Techniques; D011392:Proline / Q000378:metabolism; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism
D015850:Interleukin-6; D012709:Serum Albumin; D003094:Collagen; D011392:Proline; D017364:Collagenases