Abstract
SummaryMultiple 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.
Highlights
Multiple myeloma (MM), a haematological malignancy developed in the bone marrow, is the most common cancer involving bone and the second most prevalent cancer involving blood cells [1, 2]
Recent research into MM bone disease has revealed that the interaction between MM cells and the bone microenvironment plays an important role in the development of the condition, and a ‘vicious cycle’ of myeloma development and bone destruction is established [2,3,4]
Bortezomib stimulates osteoblast proliferation and bone formation in MM patients, which can potentially inhibit the growth of myeloma cells as well as bone destruction
Summary
Multiple myeloma (MM), a haematological malignancy developed in the bone marrow, is the most common cancer involving bone and the second most prevalent cancer involving blood cells [1, 2]. Bisphosphonate treatments target high turnover skeletal sites, binding to the mineralized bone matrix within these sites [7,8,9] After their internalization by bone-resorbing osteoclasts, bisphosphonates inhibit further osteoclast activity and bone resorption by suppressing the differentiation of osteoclast precursors into mature osteoclasts, promoting osteoclast apoptosis and disrupting osteoclast function [8, 9]. TGF-β is reported to contribute to the progression of MM-induced bone disease [5] It is released with bone resorption and stimulates the production of osteoblast progenitors but inhibits the differentiation of mature osteoblasts. It suppresses bone formation and indirectly promotes the progression of MM cells (immature osteoblast cells facilitate the growth and survival of MM cells, while mature cells enhance apoptosis of MM cells). A mathematical model we described previously [3] was extended to simulate these three different strategies and determine their efficacies in MM (Tables I and II)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International Journal for Numerical Methods in Biomedical Engineering
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
