A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease. (2nd September 2015)

• Record Type: Journal Article
• Authors: Ji, Bing; Genever, Paul G.; Fagan, Michael J.
• Is Part Of: International journal for numerical methods in biomedical engineering. Volume 32:Number 3(2016:Mar.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2015-09-02
• Subjects: multiple myeloma -- bone disease -- therapies -- mathematical model; Biomedical engineering -- Periodicals; Imaging systems in medicine -- Periodicals; Numerical analysis -- Periodicals; Engineering mathematics -- Periodicals; 610.28
• DOI: 10.1002/cnm.2735
• Languages: English
• ISSNs: 2040-7939

Abstract

Summary: 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. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd. Abstract : An extended mathematical model is developed to evaluate three therapies of multiple myeloma bone disease, namely: bisphosphonates, bortezomib and transforming growth factor β (TGF‐β) inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction but also reduce the viability of myeloma cells, while treatments designed to inhibit TGF‐β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells. These findings contribute to the current debate regarding the efficacy of these three therapies.