title: Can 11β-hydroxysteroid dehydrogenase activity predict the sensitivity of bone to therapeutic glucocorticoids in inflammatory bowel disease?
abstract: In healthy individuals measures of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme activity predict the change in bone formation markers in response to therapeutic glucocorticoids. It is unclear whether these measures remain predictive in inflammatory disease. We therefore examined whether 11β-HSD1 activity predicts changes in bone markers and bone mineral density (BMD) in patients with inflammatory bowel disease (IBD) treated with therapeutic glucocorticoids. Prospective and cross-sectional studies were carried out in patients attending a gastroenterology clinic with active (n = 39) or clinically inactive (n = 34) IBD and healthy controls (n = 51). Urinary corticosteroid metabolite profiles were obtained on a spot urine sample and total corticosteroid metabolite excretion and 11β-HSD1 activity (measured as the ratio of tetrahydrocortisol to tetrahydrocortisone metabolites, [THF+alloTHF]/THE) determined. Patients with active disease were treated with an 8-week reducing course of oral prednisolone. The (THF+alloTHF)/THE ratio was significantly increased in patients with IBD, even those in clinical remission. The baseline (THF+alloTHF)/THE ratio failed to predict the decrease in bone formation markers or hip BMD. Measures of 11β-HSD activity do not predict bone loss during glucocorticoid treatment of active IBD, probably due to disease-related increases in 11β-HSD1 activity. Our observation of elevated 11β-HSD1 activity in clinically inactive IBD implicates gastrointestinal glucocorticoid activation in the maintenance of disease remission.
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, UK. m.s.cooper@bham.ac.uk
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cooper
authors.forename: Hashir
authors.initials: H
authors.lastname: Kriel
authors.forename: Adrian
authors.initials: A
authors.lastname: Sayers
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Williams
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Chris S
authors.initials: CS
authors.lastname: Probert
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Tobias
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D001862:Bone Resorption / Q000139:chemically induced / Q000175:diagnosis* / Q000453:epidemiology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D004351:Drug Resistance / Q000502:physiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1