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Title: Investigation of the pathogenesis of bone loss associated with inflammation and steroid therapy
Author: Kriel , Muhammed Hashir
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Patients with inflammatory bowel disease (IBO), comprising Crohn's disease (CD) and ulcerative colitis (UC) are at increased risk of osteoporosis with associated fracture and morbidity, particularly at a younger age. Numerous studies in the literature have shown that disease activity and glucocorticoid (GC) use are major contributing factors. Individuals can vary in their response to GC as reflected by their Iymphocyte steroid sensitivity (LSS) in vitro and the sensitivity of bone to effects of GC can vary as well. The observation that rapid bone loss at Ward's triangle occurred in a cohort of CD patients treated for a disease relapse with a single course of glucocorticoid therapy lead to the interventional randomised control trial that formed the basis of this project and the prospective and cross-sectional investigations described in this thesis. The RCT was designed to determine whether risedronate could prevent bone loss in CD and UC patients treated with a short course of GC for a relapse. Patients recruited to the RCT provided serum and urine samples at regular intervals which were used to measure Iymphocyte steroid sensitivity (LSS), bone turnover markers (P1 NP and CTX), cytokine concentrations and 11 hydroxysteroid dehydrogenase (11BHSD1). The aim of the project was to explore mechanisms which determine the extent of bone loss in patients with IBD and to determine whether the degree of bone loss is related to individual steroid sensitivity or the extent of systemic inflammation or both of these mechanisms. Hence skeletal changes measured by DXA and bone turnover markers were related to LSS, cytokines concentrations and disease activity scores. We determined whether 11 BHSD1 could predict change in BMD or bone markers. Risedronate was effective at reducing bone loss at WT shown to our knowledge for the first time during a short course of steroid therapy. 11BHS01 did not predict bone loss but this had not been explored in' the context of IBD previously. The cross-sectional data for LSS revealed some intriguing results but may not predict clinical steroid responsiveness in all patients. Clarifying the pathogenesis of bone loss may inform strategies to minimise bone loss, but there is no clear method of predicting which patients are most susceptible to the deleterious effects of GC.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available