The effect of azathioprine on bone health

Morgan, Stephanie

Abstract

Individuals with inflammatory bowel disease (IBD) often present with poor bone health and have increased risk of osteoporotic bone fractures. The development of targeted therapies for this bone loss requires a better understanding of the underlying cellular mechanisms. Azathioprine is a commonly used drug for IBD management and has been shown to induce autophagy within the colon. However, its mechanisms of action, in particular its effects on the skeleton, are not yet fully understood. Herein, the dextran sulphate sodium (DSS) model of colitis was induced in mice to examine the effects of azathioprine treatment on bone health. Micro-computed tomography assessment of vehicle-treated DSS mice revealed a worsened trabecular bone architecture compared to vehicle-treated control mice. The azathioprine treated mice were found to have decreased bone architecture when treated with the drug alone without the presence of colitis, and there was a partial protection provided to the DSS-treated animals with azathioprine treatment However, when combined with DSS, azathioprine provides partial protection against damage to bone architecture. Histological analysis revealed that azathioprine treatment induced autophagy in the bone. This indicates that azathioprine reduces bone health in an in vivo a model of IBD. This therefore suggests that azathioprine treatment may have a deleterious effect on IBD patients who may already be at increased risk of osteoporotic bone fractures and thus will inform on future treatment strategies for patient stratification.

Citation

Morgan, S. The effect of azathioprine on bone health. (Thesis). Edinburgh Napier University. http://researchrepository.napier.ac.uk/Output/2386593

• Thesis Type: Thesis
• Deposit Date: Dec 10, 2019
• Publicly Available Date: Dec 10, 2019
• Keywords: bone health; inflammatory bowel disease; autophagy; colitis; osteoporosis; azathioprine
• Public URL: http://researchrepository.napier.ac.uk/Output/2386593
• Award Date: Oct 31, 2019