Mette Reilev1, Jesper Hallas1, Martin Thomsen Ernst1,2, Gunnar Lauge Nielsen3,4, Ole K Bonderup5. 1. Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense University Hospital, Odense, Denmark. 2. OPEN - Open Patient data Explorative Network, Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 3. Department of Internal Medicine, Aalborg University Hospital, Aalborg, Denmark. 4. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 5. Diagnostic Centre, Regional Hospital Silkeborg, and University Research Clinic for Innovative Patient Pathways, Aarhus University, Aarhus, Denmark.
Abstract
BACKGROUND: Due to a substantial first-pass metabolism of oral budesonide, systemic bioavailability is low compared to other oral corticosteroids, thereby possibly avoiding adverse effects of systemic corticosteroid use. AIM: To determine whether use of oral budesonide is associated with osteoporotic fractures in patients with microscopic colitis (MC). METHODS: Applying data from the Danish nationwide health registries, we conducted a case-control study nested within a cohort of patients with MC from 2004 to 2012. We estimated odds ratios (ORs) for the association between budesonide use and osteoporotic fractures (hip, wrist and spinal fractures). RESULTS: We identified 417 cases with a first occurrence of an osteoporotic fracture. Eighty-six per cent were women and the median age was 78 years. The OR for the overall association between ever-use of budesonide and any osteoporotic fractures did not reach statistical significance (OR 1.13, CI: 0.88-1.47). The highest risk was observed for spinal fractures (OR 1.98, CI: 0.94-4.17), where a dose-response association seemed to exist, followed by hip and wrist fractures (OR 1.17 [CI: 0.79-1.73] and OR 0.99 [CI: 0.66-1.47] respectively). We generally found modestly increased ORs across subgroups at suspected high or low risk of fractures (1.00-2.49). No overall dose-response association was evident (OR for doubling of cumulative dose 0.93 (CI: 0.84-1.03). CONCLUSION: No overall association between use of oral budesonide and osteoporotic fractures was demonstrated among individuals with MC. There seemed to be an isolated adverse effect of budesonide on the risk of spinal fractures, which appears to be dose related.
BACKGROUND: Due to a substantial first-pass metabolism of oral budesonide, systemic bioavailability is low compared to other oral corticosteroids, thereby possibly avoiding adverse effects of systemic corticosteroid use. AIM: To determine whether use of oral budesonide is associated with osteoporotic fractures in patients with microscopic colitis (MC). METHODS: Applying data from the Danish nationwide health registries, we conducted a case-control study nested within a cohort of patients with MC from 2004 to 2012. We estimated odds ratios (ORs) for the association between budesonide use and osteoporotic fractures (hip, wrist and spinal fractures). RESULTS: We identified 417 cases with a first occurrence of an osteoporotic fracture. Eighty-six per cent were women and the median age was 78 years. The OR for the overall association between ever-use of budesonide and any osteoporotic fractures did not reach statistical significance (OR 1.13, CI: 0.88-1.47). The highest risk was observed for spinal fractures (OR 1.98, CI: 0.94-4.17), where a dose-response association seemed to exist, followed by hip and wrist fractures (OR 1.17 [CI: 0.79-1.73] and OR 0.99 [CI: 0.66-1.47] respectively). We generally found modestly increased ORs across subgroups at suspected high or low risk of fractures (1.00-2.49). No overall dose-response association was evident (OR for doubling of cumulative dose 0.93 (CI: 0.84-1.03). CONCLUSION: No overall association between use of oral budesonide and osteoporotic fractures was demonstrated among individuals with MC. There seemed to be an isolated adverse effect of budesonide on the risk of spinal fractures, which appears to be dose related.
Authors: Stephan Miehlke; Danila Guagnozzi; Yamile Zabana; Gian E Tontini; Anne-Marie Kanstrup Fiehn; Signe Wildt; Johan Bohr; Ole Bonderup; Gerd Bouma; Mauro D'Amato; Peter J Heiberg Engel; Fernando Fernandez-Banares; Gilles Macaigne; Henrik Hjortswang; Elisabeth Hultgren-Hörnquist; Anastasios Koulaouzidis; Jouzas Kupcinskas; Stefania Landolfi; Giovanni Latella; Alfredo Lucendo; Ivan Lyutakov; Ahmed Madisch; Fernando Magro; Wojciech Marlicz; Emese Mihaly; Lars K Munck; Ann-Elisabeth Ostvik; Árpád V Patai; Plamen Penchev; Karolina Skonieczna-Żydecka; Bas Verhaegh; Andreas Münch Journal: United European Gastroenterol J Date: 2021-02-22 Impact factor: 4.623