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-kappaB (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.
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-kappaB (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 IBDpatients 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 IBDpatients (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.
Authors: E Kokkotou; L A Conboy; D C Ziogas; M T Quilty; J M Kelley; R B Davis; A J Lembo; T J Kaptchuk Journal: Neurogastroenterol Motil Date: 2009-12-22 Impact factor: 3.598
Authors: Sundaram G Veerappan; Martin Healy; Bernard J Walsh; Colm A O'Morain; Jacqueline S Daly; Barbara M Ryan Journal: Dig Dis Sci Date: 2015-03-03 Impact factor: 3.199
Authors: Jamal A Mohamed; Herbert L DuPont; Zhi-Dong Jiang; Jose Flores; Lily G Carlin; Jaime Belkind-Gerson; Francisco G Martinez-Sandoval; Dongchuan Guo; A Clinton White; Pablo C Okhuysen Journal: J Infect Dis Date: 2009-02-15 Impact factor: 5.226
Authors: Ioannis Karatzoglou; Maria P Yavropoulou; Maria Pikilidou; George Germanidis; Evangelos Akriviadis; Alexandra Papazisi; Michael Daniilidis; Pantelis Zebekakis; John G Yovos Journal: World J Gastroenterol Date: 2014-07-28 Impact factor: 5.742