title: Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease.
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.
authors.affiliation: School of Control Science and Engineering, Shandong University, 17923 Jingshi Road, Jinan, 250061, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ji
authors.forename: Paul G
authors.initials: PG
authors.lastname: Genever
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Patton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fagan
mesh_terms: D000465:Algorithms; D001847:Bone Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D009101:Multiple Myeloma / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D016212:Transforming Growth Factor beta
keywords: MM-induced bone disease; bone microenvironment; mathematical model; multiple myeloma; osteoblast and osteoclast activities