Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease

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

Abstract

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets.

Citation

Ji, B., Genever, P. G., Patton, R. J., & Fagan, M. J. (2014). Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease. International journal for numerical methods in biomedical engineering, 30(11), 1085-1102. https://doi.org/10.1002/cnm.2645

• Journal Article Type: Article
• Acceptance Date: Mar 28, 2014
• Online Publication Date: May 9, 2014
• Publication Date: 2014-11
• Deposit Date: Jun 3, 2015
• Publicly Available Date: Jun 3, 2015
• Journal: International journal for numerical methods in biomedical engineering
• Print ISSN: 2040-7939
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 30
• Issue: 11
• Pages: 1085-1102
• DOI: https://doi.org/10.1002/cnm.2645
• Keywords: Multiple myeloma, MM-induced bone disease, Bone microenvironment, Mathematical model, Osteoblast and osteoclast activities
• Public URL: https://hull-repository.worktribe.com/output/374658
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/cnm.2645/abstract;jsessionid=D555DB2E2BE76CED928229CE5982F100.f04t04
• Additional Information: Copy of an article published in International journal for numerical methods in biomedical engineering, 2014, v.30 at http://dx.doi.org/10.1002/cnm.2645
• Contract Date: Jun 3, 2015