title: A mathematical model of bone remodeling dynamics for normal bone cell populations and myeloma bone disease.
abstract: BACKGROUND
  Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease.
  
  
  RESULTS
  Mathematical models are developed for normal bone remodeling and for the dysregulated bone remodeling that occurs in myeloma bone disease. The models examine the critical signaling between osteoclasts (bone resorption) and osteoblasts (bone formation). The interactions of osteoclasts and osteoblasts are modeled as a system of differential equations for these cell populations, which exhibit stable oscillations in the normal case and unstable oscillations in the myeloma case. In the case of untreated myeloma, osteoclasts increase and osteoblasts decrease, with net bone loss as the tumor grows. The therapeutic effects of targeting both myeloma cells and cells of the bone marrow microenvironment on these dynamics are examined.
  
  
  CONCLUSIONS
  The current model accurately reflects myeloma bone disease and illustrates how treatment approaches may be investigated using such computational approaches.
  
  
  METHODS
  This article was reviewed by Ariosto Silva and Mark P. Little.
authors.affiliation: Department of Mathematics, University of Iowa, Iowa City, IA 52242, USA. ayati@math.uiowa.edu
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Ayati
authors.forename: Claire M
authors.initials: CM
authors.lastname: Edwards
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Webb
authors.forename: John P
authors.initials: JP
authors.lastname: Wikswo
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D006801:Humans; D008962:Models, Theoretical; D009101:Multiple Myeloma / Q000473:pathology*; D010010:Osteoclasts / Q000166:cytology*; D010011:Osteocytes / Q000166:cytology*
references.citation: PLoS One. 2008 May 07;3(5):e2104
references.pmid: 18461134
references.citation: J Bone Miner Res. 2009 May;24(5):860-70
references.pmid: 19063683
references.citation: Br J Haematol. 1982 Dec;52(4):601-10
references.pmid: 7138789
references.citation: Eur J Haematol. 1998 Aug;61(2):128-34
references.pmid: 9714526
references.citation: Br J Haematol. 2006 Dec;135(5):688-92
references.pmid: 17107351
references.citation: J Clin Invest. 2003 Jun;111(11):1771-82
references.pmid: 12782679
references.citation: N Engl J Med. 1974 Nov 14;291(20):1041-6
references.pmid: 4413338
references.citation: J Cell Biochem. 1994 Jul;55(3):273-86
references.pmid: 7962158
references.citation: J Bone Miner Metab. 2005;23(1):1-7
references.pmid: 15616887
references.citation: Bone. 2004 Oct;35(4):918-28
references.pmid: 15454099
references.citation: J Clin Invest. 1991 Jul;88(1):62-6
references.pmid: 2056131
references.citation: Cancer. 1990 Jul 1;66(1):167-72
references.pmid: 2354403
references.citation: Am J Hematol. 2009 May;84(5):268-72
references.pmid: 19296472
references.citation: Clin Chem. 2001 Apr;47(4):686-93
references.pmid: 11274019
references.citation: Blood. 2008 Oct 1;112(7):2935-45
references.pmid: 18535198
references.citation: Bone. 2003 Aug;33(2):206-15
references.pmid: 14499354
references.citation: Eur J Cancer. 1998 Feb;34(2):246-51
references.pmid: 9741328
references.citation: Nature. 2008 Jul 10;454(7201):221-5
references.pmid: 18548006
references.citation: Conf Proc IEEE Eng Med Biol Soc. 2006;2006:3154-7
references.pmid: 17947010
references.citation: Br J Haematol. 2007 Nov;139(3):434-8
references.pmid: 17910634
references.citation: Endocrinology. 2005 Aug;146(8):3589-95
references.pmid: 15860557
references.citation: Cancer Res. 2001 Apr 1;61(7):3071-6
references.pmid: 11306489
references.citation: Cancer Res. 2002 Sep 1;62(17):4996-5000
references.pmid: 12208752
references.citation: Biochem Biophys Res Commun. 2005 Jul 22;333(1):200-5
references.pmid: 15936724
references.citation: J Bone Joint Surg Br. 1989 Mar;71(2):288-90
references.pmid: 2925748
references.citation: Clin Lymphoma Myeloma. 2007 Nov;7(9):587-9
references.pmid: 18186967
references.citation: Eur J Haematol. 1992 Oct;49(4):192-8
references.pmid: 1464362
references.citation: Am J Hematol. 2009 Jan;84(1):6-14
references.pmid: 18980173
references.citation: Comput Methods Biomech Biomed Engin. 2009 Jun;12(3):341-52
references.pmid: 19089785
references.citation: J Theor Biol. 2004 Aug 7;229(3):293-309
references.pmid: 15234198
references.citation: Leuk Res. 2001 Oct;25(10):901-7
references.pmid: 11532524
references.citation: Biomech Model Mechanobiol. 2005 Nov;4(2-3):147-67
references.pmid: 15942795
references.citation: Biophys Chem. 2007 May;127(3):194-212
references.pmid: 17321664
references.citation: Bone. 2008 Aug;43(2):249-63
references.pmid: 18514606
references.citation: J Biomed Mater Res. 2002 May;60(2):292-9
references.pmid: 11857436
references.citation: Ann N Y Acad Sci. 2006 Apr;1068:557-9
references.pmid: 16831951