OBJECTIVE: Osteoporosis is a common complication of Crohn's disease (CD). Glucocorticoid use and detrimental effects of inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) can lead to osteoporosis. The aim of this study was to assess the ability of treatment with the TNF-alpha antagonist infliximab to increase bone formation as measured by surrogate markers of bone turnover in patients with active CD. METHODS: Sera from 38 prospectively enrolled CD patients were examined for levels of bone alkaline phosphatase (BAP), N-telopeptide of type I collagen (NTX), immunoreactive parathyroid hormone (iPTH), calcium, and pro-inflammatory cytokines at baseline and 4 weeks following infliximab infusion. Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and glucocorticoid dose also were collected. RESULTS: In this cohort, CDAI and IBDQ scores were significantly improved at week 4 (P<0.001). Infliximab therapy was associated with an increase in BAP, a marker of bone formation (P=0.010), whereas NTX, a marker of bone resorption, was not increased (P=0.801). Among 22 patients who were taking glucocorticoids, mean glucocorticoid dose decreased 36% (P<0.001; -7.9 mg). CONCLUSIONS: Treatment with infliximab was associated with increased markers of bone formation (BAP) without increasing bone resorption (NTX). This effect may be due to a beneficial effect of TNF-alpha blockade on bone turnover, a beneficial effect on CD activity resulting in decreased glucocorticoid dose, or both. Studies of longer duration are needed to assess the effect of infliximab on bone mineral density.
OBJECTIVE:Osteoporosis is a common complication of Crohn's disease (CD). Glucocorticoid use and detrimental effects of inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) can lead to osteoporosis. The aim of this study was to assess the ability of treatment with the TNF-alpha antagonist infliximab to increase bone formation as measured by surrogate markers of bone turnover in patients with active CD. METHODS: Sera from 38 prospectively enrolled CDpatients were examined for levels of bone alkaline phosphatase (BAP), N-telopeptide of type I collagen (NTX), immunoreactive parathyroid hormone (iPTH), calcium, and pro-inflammatory cytokines at baseline and 4 weeks following infliximab infusion. Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and glucocorticoid dose also were collected. RESULTS: In this cohort, CDAI and IBDQ scores were significantly improved at week 4 (P<0.001). Infliximab therapy was associated with an increase in BAP, a marker of bone formation (P=0.010), whereas NTX, a marker of bone resorption, was not increased (P=0.801). Among 22 patients who were taking glucocorticoids, mean glucocorticoid dose decreased 36% (P<0.001; -7.9 mg). CONCLUSIONS: Treatment with infliximab was associated with increased markers of bone formation (BAP) without increasing bone resorption (NTX). This effect may be due to a beneficial effect of TNF-alpha blockade on bone turnover, a beneficial effect on CD activity resulting in decreased glucocorticoid dose, or both. Studies of longer duration are needed to assess the effect of infliximab on bone mineral density.
Authors: Judith Pichler; Wolf Dietrich Huber; Christoph Aufricht; Bettina Bidmon-Fliegenschnee Journal: World J Gastroenterol Date: 2015-06-07 Impact factor: 5.742
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: Lindsay M Griffin; Meena Thayu; Robert N Baldassano; Mark D DeBoer; Babette S Zemel; Michelle R Denburg; Lee A Denson; Justine Shults; Rita Herskovitz; Jin Long; Mary B Leonard Journal: J Clin Endocrinol Metab Date: 2015-04-28 Impact factor: 5.958