title: A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease.
abstract: 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.
authors.affiliation: School of Control Science and Engineering, Shandong University, Jinan, 250061, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ji
authors.affiliation: Department of Biology, University of York, York, YO10 5DD, UK.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Genever
authors.affiliation: School of Engineering, University of Hull, Hull, HU6 7RX, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fagan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001847:Bone Diseases / Q000188:drug therapy* / Q000209:etiology*; D000069286:Bortezomib / Q000494:pharmacology / Q000627:therapeutic use; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D014584:User-Computer Interface
chemical_list: D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta; D000069286:Bortezomib
keywords: bone disease; mathematical model; multiple myeloma; therapies