Serum osteoprotegerin is increased in Crohn's disease: A population-based case control study
Article first published online: 14 DEC 2006
Copyright © 2005 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 11, Issue 4, pages 325–330, April 2005
How to Cite
Bernstein, C. N., Sargent, M. and Leslie, W. D. (2005), Serum osteoprotegerin is increased in Crohn's disease: A population-based case control study. Inflamm Bowel Dis, 11: 325–330. doi: 10.1097/01.MIB.0000164015.60795.ca
- Issue published online: 14 DEC 2006
- Article first published online: 14 DEC 2006
- Manuscript Accepted: 26 DEC 2004
- Manuscript Received: 16 JUL 2004
- Canadian Institutes of Health Research
- Crohn's disease;
- inflammatory bowel disease;
- receptor for activated nuclear factor kappa-B;
- ulcerative colitis
Background: There is a potential interface between osteoporosis and the chronic inflammation of inflammatory bowel disease (IBD), and the osteoprotegerin (OPG)/receptor for activated nuclear factor-κB (RANK)/RANK ligand (RANKL) signaling pathway may be an important mediator, although data are limited.
Methods: We conducted a population-based case-control seroassay study to look for alterations in serum OPG and soluble RANKL (sRANKL). The study population included IBD patients who were 18 to 50 years old with Crohn's disease (CD; n = 287) or ulcerative colitis (UC; n = 166), age-matched healthy controls (n = 368), and nonaffected siblings of IBD patients (n = 146). Serum OPG and sRANKL were measured by enzyme-linked immunoassay. Sex-specific reference ranges were derived from the healthy controls.
Results: Analysis of variance (ANOVA) confirmed significant group differences in women for mean serum OPG (P = 0.018). CD women had higher values of OPG than UC women (P = 0.028) or healthy controls (P = 0.045), whereas the other groups were similar. OPG levels were above the reference range in 13/173 (8%) of CD women, exceeding the expected proportion (P = 0.032). In contrast, no differences in OPG were seen in men between controls, CD, or UC. Estrogen use in women (P = 0.000002) and corticosteroid use in men (P = 0.026) were associated with higher OPG levels. In multivariate analysis, CD diagnosis (P = 0.031) and estrogen use (P = 0.000002) were independently associated with higher OPG levels. No group differences were seen in mean serum sRANKL measurements.
Conclusions: An OPG:sRANKL imbalance with OPG exceeding sRANKL should inhibit osteoclastogenesis and promote bone formation. CD is associated with increased fracture risk, and possibly, the paradoxically higher OPG is a counterregulatory response to factors such as inflammatory cytokines, promoting high bone turnover. Alternatively, elevated OPG in CD may reflect T-cell activation.