title: A mathematical model of cell equilibrium and joint cell formation in multiple myeloma.
abstract: In Multiple Myeloma Bone Disease healthy bone remodelling is affected by tumour cells by means of paracrine cytokinetic signalling in such a way that osteoclast formation is enhanced and the growth of osteoblast cells inhibited. The participating cytokines are described in the literature. Osteoclast-induced myeloma cell growth is also reported. Based on existing mathematical models for healthy bone remodelling a three-way equilibrium model is presented for osteoclasts, osteoblasts and myeloma cell populations to describe the progress of the illness in a scenario in which there is a secular increase in the cytokinetic interactive effectiveness of paracrine processes. The equilibrium state for the system is obtained. The paracrine interactive effectiveness is explored by parameter variation and the stable region in the parameter space is identified. Then recently-discovered joint myeloma-osteoclast cells are added to the model to describe the populations inside lytic lesions. It transpires that their presence expands the available parameter space for stable equilibrium, thus permitting a detrimental, larger population of osteoclasts and myeloma cells. A possible relapse mechanism for the illness is explored by letting joint cells dissociate. The mathematics then permits the evaluation of the evolution of the cell populations as a function of time during relapse.
authors.affiliation: Department Engineering and The Environment, University of Southampton, Highfield, Southampton SO17 1BJ, UK. Electronic address: c_koenders@yahoo.com.
authors.forename: M A
authors.initials: MA
authors.lastname: Koenders
authors.affiliation: Bud Flanagan Ambulatory Outpatients Unit, The Royal Marsden, Downs Road, Sutton, Surrey SM2 5 PT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Saso
mesh_terms: D000465:Algorithms; D016723:Bone Remodeling; D002450:Cell Communication; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D015398:Signal Transduction
chemical_list: D016207:Cytokines
keywords: Joint myeloma/osteoclast cells; Mathematical modelling; Multiple myeloma; Paracrine cytokines