Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice

Holgersen, K., Dobie, R., Farquharson, C., vanʼt Hof, R., Ahmed, S. F. , Hansen, A. K. and Holm, T. L. (2015) Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice. Inflammatory Bowel Diseases, 21(2), pp. 257-266. (doi: 10.1097/MIB.0000000000000269) (PMID:25569742) (PMCID:25569742)

Abstract

Background: Osteoporosis and fractures are common complications of inflammatory bowel disease. The pathogenesis is multifactorial and has been partly attributed to intestinal inflammation. The aim of this study was to evaluate bone status and assess the association between bone loss and gut inflammation in an experimental colitis model.<p></p> Methods: Colitis was induced in interleukin-10 knockout mice (PAC IL-10 k.o.) by peroral administration of piroxicam for 12 days. The degree of colitis was assessed by clinical, macroscopic, and microscopic evaluation. Trabecular and cortical bone microarchitecture of tibia were determined using micro-computed tomography. Moreover, the serum levels of bone formation and bone resorption biomarkers were measured, and inflammatory protein profiling was performed on colons.<p></p> Results: PAC IL-10 k.o. mice developed severe colitis, characterized by hyperplasia and focal transmural inflammation, which was consistent with Crohn's disease-like pathology. The gut inflammation was accompanied by a 14% and 12% reduction in trabecular thickness relative to piroxicam-treated wild type and untreated wild type mice, respectively (P < 0.001). The trabecular bone structure was also changed in PAC IL-10 k.o. mice, whereas no differences in cortical bone geometry were observed. The trabecular thickness was inversely correlated with serum levels of CTX (r = -0.93, P = 0.006). Moreover, numerous inflammatory mediators, including RANKL and osteoprotegerin, were significantly increased in the colon of PAC IL-10 k.o. mice.<p></p> Conclusions: PAC IL-10 k.o. mice develop bone loss and changed trabecular structure, as a result of increased bone resorption. Thus, the PAC IL-10 k.o. model could be a useful experimental model in preclinical research of inflammatory bowel disease-associated bone loss.<p></p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ahmed, Professor Syed Faisal
• Authors: Holgersen, K., Dobie, R., Farquharson, C., vanʼt Hof, R., Ahmed, S. F., Hansen, A. K., and Holm, T. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Inflammatory Bowel Diseases
• Publisher: Wiley
• ISSN: 1078-0998
• ISSN (Online): 1536-4844