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. © 2014 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd
Highlights
Multiple myeloma (MM) is the second most frequent haematological malignancy, and MM-induced bone disease is a major cause of morbidity for MM patients [1]
Many biochemical factors have been implicated in the development of MM-induced bone disease, for example, cytokines with osteoclast activating function, such as the receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor, interleukin-6 (IL-6), IL-11 and IL-1β [7], which are produced or
IL-6 secreted by bone marrow stromal cell (BMSC) stimulates the production of RANKL by osteoblast precursors [28], while MM cells suppress the production of OPG by mature osteoblasts [7]
Summary
Multiple myeloma (MM) is the second most frequent haematological malignancy, and MM-induced bone disease is a major cause of morbidity for MM patients [1]. MM induces increased bone resorption and suppressed bone formation leading to a negative bone balance and osteolytic lesions that rarely heal [2, 3]. The interaction between MM cells and the bone microenvironment (MM–bone interaction) plays an important role in the development of MM-induced bone disease. It promotes tumour growth and survival, as well as the consequent bone destruction [1]. Many biochemical factors have been implicated in the development of MM-induced bone disease, for example, cytokines with osteoclast activating function, such as the receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor, interleukin-6 (IL-6), IL-11 and IL-1β [7], which are produced or
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