A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease: Modelling Therapies for Multiple Myeloma Induced Bone Disease

Ji, Bing; Genever, Paul G.; Fagan, Michael J.

Abstract

Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma-induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF-β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti-tumour effect. On the other hand, the analyses indicate that treatments designed to inhibit TGF-β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells, which again contributes to the current controversy regarding the efficacy of TGF-β inhibition in multiple myeloma-induced bone disease.

Citation

Ji, B., Genever, P. G., & Fagan, M. J. (2016). A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease: Modelling Therapies for Multiple Myeloma Induced Bone Disease. International journal for numerical methods in biomedical engineering, 32(3), e02735. https://doi.org/10.1002/cnm.2735

• Journal Article Type: Article
• Acceptance Date: Jul 13, 2015
• Online Publication Date: Sep 2, 2015
• Publication Date: 2016-03
• Deposit Date: Oct 27, 2015
• Publicly Available Date: Nov 23, 2017
• Journal: International journal for numerical methods in biomedical engineering
• Print ISSN: 2040-7939
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 3
• Pages: e02735
• DOI: https://doi.org/10.1002/cnm.2735
• Keywords: Multiple myeloma, Bone disease, Therapies, Mathematical model
• Public URL: https://hull-repository.worktribe.com/output/380253
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/cnm.2735/abstract
• Additional Information: Copy of article first published in: International journal for numerical methods in biomedical engineering, 2015.
• Contract Date: Nov 23, 2017