Skip to main content
SpringerLink
Log in

Osteoclasts: Potential Target for Blocking Microenvironmental Support of Myeloma

  • Chapter
  • First Online:
Advances in Biology and Therapy of Multiple Myeloma

Abstract

Multiple myeloma (MM) bone disease is a major contributor to the morbidity and mortality of MM patients due to pathological fractures. The MM cells interact with the cells of the bone microenvironment to both generate bone lesions as a result of enhanced induction of osteoclastogenesis and prevent reactive new bone formation to heal the lesions by repressing osteoblast activity. The MM stimulated osteoclasts (OCLs) not only generate bone lesions, but also interact with the myeloma cells to promote the proliferation and survival of the MM cells through the generation of interleukin-6 (IL-6), osteopontin, fibroblast activation protein, BAFF, APRIL, and annexin II. These MM-supportive OCL products present therapeutic opportunities. Further, the enhanced bone resorption by OCLs releases immobilized growth factors from the bone matrix that both support the MM cells and further stimulate OCL differentiation in a vicious cycle. Hence, targeting osteoclast activity may inhibit myeloma growth. Therefore, bisphosphonates have been investigated for their anti-tumor affects. The MM cells increase osteoclast activity both directly and by stimulation of microenvironmental production of RANKL, MIP-1α, TNF-α and interleukins IL-1b, IL-3 and IL-6. These are therefore also possible therapeutic targets to inhibit myeloma bone disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Roodman GD (2004) Pathogenesis of myeloma bone disease. Blood Cells Mol Dis 32:290–292

    Article  PubMed  CAS  Google Scholar 

  2. Melton LJ 3rd, Kyle RA, Achenbach SJ et al (2005) Fracture risk with multiple myeloma: a population-based study. J Bone Miner Res 20:487–493

    Article  PubMed  Google Scholar 

  3. Taube T, Beneton MN, McCloskey EV et al (1992) Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption. Eur J Haematol 49:192–198

    Article  PubMed  CAS  Google Scholar 

  4. Yaccoby S, Wezeman MJ, Henderson A et al (2004) Cancer and the microenvironment: myeloma-osteoclast interactions as a model. Cancer Res 64:2016–2023

    Article  PubMed  CAS  Google Scholar 

  5. Abe M, Hiura K, Wilde J et al (2004) Osteoclasts enhance myeloma cell growth and survival via cell–cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood 104:2484–2491

    Article  PubMed  CAS  Google Scholar 

  6. Ge Y, Zhan F, Barlogie B et al (2006) Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival. Br J Haematol 133:83–92. doi:10.1111/j.1365-2141.2006.05976.x

    Article  PubMed  CAS  Google Scholar 

  7. Pennisi A, Li X, Ling W et al (2009) Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease. Br J Haematol 145:775–787. doi:10.1111/j.1365-2141.2009.07696.x

    Article  PubMed  CAS  Google Scholar 

  8. Tanaka Y, Abe M, Hiasa M et al (2007) Myeloma cell–osteoclast interaction enhances angiogenesis together with bone resorption: a role for vascular endothelial cell growth factor and osteopontin. Clin Cancer Res 13:816–823. doi:10.1158/1078-0432.CCR-06-2258

    Article  PubMed  CAS  Google Scholar 

  9. Abe M, Kido S, Hiasa M et al (2006) BAFF and APRIL as osteoclast-derived survival factors for myeloma cells: a rationale for TACI-Fc treatment in patients with multiple myeloma. Leukemia 20:1313–1315. doi:10.1038/sj.leu.2404228

    Article  PubMed  CAS  Google Scholar 

  10. D’Souza S, Shiozawa Y, Galson DL et al (2009) Annexin II and Annexin II receptor interactions enhance multiple myeloma growth in the bone marrow microenvironment. In: The IX international meeting on cancer induced bone disease, Arlington, VA (Abstract)

    Google Scholar 

  11. Bao H, Jiang M, Zhu M et al (2009) Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol 90:177–185. doi:10.1007/s12185-009-0356-8

    Article  PubMed  CAS  Google Scholar 

  12. Takahashi S, Reddy SV, Chirgwin JM et al (1994) Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. J Biol Chem 269:28696–28701

    PubMed  CAS  Google Scholar 

  13. Menaa C, Devlin RD, Reddy SV et al (1999) Annexin II increases osteoclast formation by stimulating the proliferation of osteoclast precursors in human marrow cultures. J Clin Invest 103:1605–1613

    Article  PubMed  CAS  Google Scholar 

  14. Cole SP, Pinkoski MJ, Bhardwaj G et al (1992) Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line. Br J Cancer 65:498–502

    Article  PubMed  CAS  Google Scholar 

  15. Shinar DM, Schmidt A, Halperin D et al (1993) Expression of alpha v and beta 3 integrin subunits in rat osteoclasts in situ. J Bone Miner Res 8:403–414

    Article  PubMed  CAS  Google Scholar 

  16. Vishwanatha JK, Chiang Y, Kumble KD et al (1993) Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis 14:2575–2579

    Article  PubMed  CAS  Google Scholar 

  17. Emoto K, Sawada H, Yamada Y et al (2001) Annexin II overexpression is correlated with poor prognosis in human gastric carcinoma. Anticancer Res 21:1339–1345

    PubMed  CAS  Google Scholar 

  18. Claudio JO, Masih-Khan E, Tang H et al (2002) A molecular compendium of genes expressed in multiple myeloma. Blood 100:2175–2186. doi:10.1182/blood-2002-01-0008

    Article  PubMed  CAS  Google Scholar 

  19. Zimmermann U, Woenckhaus C, Pietschmann S et al (2004) Expression of annexin II in conventional renal cell carcinoma is correlated with Fuhrman grade and clinical outcome. Virchows Arch 445:368–374. doi:10.1007/s00428-004-1103-4

    Article  PubMed  CAS  Google Scholar 

  20. Sharma MR, Koltowski L, Ownbey RT et al (2006) Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol 81:146–156. doi:10.1016/j.yexmp.2006.03.003

    Article  PubMed  CAS  Google Scholar 

  21. Shiozawa Y, Havens AM, Jung Y et al (2008) Annexin II/Annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 370:370–380. doi:10.1002/jcb.21835

    Article  Google Scholar 

  22. Li F, Chung H, Reddy SV et al (2005) Annexin II stimulates RANKL expression through MAPK. J Bone Miner Res 20:1161–1167

    Article  PubMed  CAS  Google Scholar 

  23. Costes V, Portier M, Lu ZY et al (1998) Interleukin-1 in multiple myeloma: producer cells and their role in the control of IL-6 production. Br J Haematol 103:1152–1160

    Article  PubMed  CAS  Google Scholar 

  24. Choi SJ, Cruz JC, Craig F et al (2000) Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood 96:671–675

    PubMed  CAS  Google Scholar 

  25. Giuliani N, Colla S, Rizzoli V (2004) New insight in the mechanism of osteoclast activation and formation in multiple myeloma: focus on the receptor activator of NF-kappaB ligand (RANKL). Exp Hematol 32:685–691

    Article  PubMed  CAS  Google Scholar 

  26. Lee JW, Chung HY, Ehrlich LA et al (2004) IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood 103:2308–2315

    Article  PubMed  CAS  Google Scholar 

  27. Gunn WG, Conley A, Deininger L et al (2006) A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: a potential role in the development of lytic bone disease and tumor progression in multiple myeloma. Stem Cells 24:986–991

    Article  PubMed  CAS  Google Scholar 

  28. Ehrlich LA, Roodman GD (2005) The role of immune cells and inflammatory cytokines in Paget’s disease and multiple myeloma. Immunol Rev 208:252–266

    Article  PubMed  CAS  Google Scholar 

  29. Sezer O, Heider U, Jakob C et al (2002) Immunocytochemistry reveals RANKL expression of myeloma cells. Blood 99:4646–4647

    Article  PubMed  CAS  Google Scholar 

  30. Giuliani N, Colla S, Sala R et al (2002) Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood 100:4615–4621

    Article  PubMed  CAS  Google Scholar 

  31. Pearse RN, Sordillo EM, Yaccoby S et al (2001) Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci USA 98:11581–11586

    Article  PubMed  CAS  Google Scholar 

  32. Menu E, Asosingh K, Van Riet I et al (2004) Myeloma cells (5TMM) and their interactions with the marrow microenvironment. Blood Cells Mol Dis 33:111–119. doi:10.1016/j.bcmd.2004.04.012

    Article  PubMed  Google Scholar 

  33. Epstein J, Yaccoby S (2005) The SCID-hu myeloma model. Methods Mol Med 113:183–190. doi:10.1385/1-59259-916-8:183

    PubMed  Google Scholar 

  34. Oba Y, Lee JW, Ehrlich LA et al (2005) MIP-1alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells. Exp Hematol 33:272–278

    Article  PubMed  CAS  Google Scholar 

  35. Vallet S, Raje N, Ishitsuka K et al (2007) MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. Blood 110:3744–3752. doi:10.1182/blood-2007-05-093294

    Article  PubMed  CAS  Google Scholar 

  36. Menu E, De Leenheer E, De Raeve H et al (2006) Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clin Exp Metastasis 23:291–300. doi:10.1007/s10585-006-9038-6

    Article  PubMed  CAS  Google Scholar 

  37. Wei S, Kitaura H, Zhou P et al (2005) IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 115:282–290. doi:10.1172/JCI23394

    PubMed  CAS  Google Scholar 

  38. Lam J, Takeshita S, Barker JE et al (2000) TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 106:1481–1488. doi:10.1172/JCI11176

    Article  PubMed  CAS  Google Scholar 

  39. Nakamura I, Jimi E (2006) Regulation of osteoclast differentiation and function by interleukin-1. Vitam Horm 74:357–370. doi:10.1016/S0083-6729(06)74015-8

    Article  PubMed  CAS  Google Scholar 

  40. Sati HI, Greaves M, Apperley JF et al (1999) Expression of interleukin-1beta and tumour necrosis factor-alpha in plasma cells from patients with multiple myeloma. Br J Haematol 104:350–357

    Article  PubMed  CAS  Google Scholar 

  41. Tsimberidou AM, Waddelow T, Kantarjian HM et al (2003) Pilot study of recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein (TNFR:Fc; Enbrel) in patients with refractory multiple myeloma: increase in plasma TNF alpha levels during treatment. Leuk Res 27:375–380. doi:S0145212602000826 [pii]

    Article  PubMed  CAS  Google Scholar 

  42. Lust JA, Lacy MQ, Zeldenrust SR et al (2009) Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc 84:114–122. doi:10.4065/84.2.114

    Article  PubMed  CAS  Google Scholar 

  43. Merico F, Bergui L, Gregoretti MG et al (1993) Cytokines involved in the progression of multiple myeloma. Clin Exp Immunol 92:27–31

    Article  PubMed  CAS  Google Scholar 

  44. Barton BE, Mayer R (1989) IL-3 induces differentiation of bone marrow precursor cells to osteoclast-like cells. J Immunol 143:3211–3216

    PubMed  CAS  Google Scholar 

  45. Solary E, Guiguet M, Zeller V et al (1992) Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma. Am J Hematol 39:163–171

    Article  PubMed  CAS  Google Scholar 

  46. Sati HI, Apperley JF, Greaves M et al (1998) Interleukin-6 is expressed by plasma cells from patients with multiple myeloma and monoclonal gammopathy of undetermined significance. Br J Haematol 101:287–295

    Article  PubMed  CAS  Google Scholar 

  47. Abildgaard N, Glerup H, Rungby J et al (2000) Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. Eur J Haematol 64:121–129

    Article  PubMed  CAS  Google Scholar 

  48. Roodman GD, Kurihara N, Ohsaki Y et al (1992) Interleukin 6. A potential autocrine/paracrine factor in Paget’s disease of bone J Clin Invest 89:46–52

    CAS  Google Scholar 

  49. Palmqvist P, Persson E, Conaway HH et al (2002) IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae. J Immunol 169:3353–3362

    PubMed  CAS  Google Scholar 

  50. Karadag A, Oyajobi BO, Apperley JF et al (2000) Human myeloma cells promote the production of interleukin 6 by primary human osteoblasts. Br J Haematol 108:383–390

    Article  PubMed  CAS  Google Scholar 

  51. Anderson KC, Jones RM, Morimoto C et al (1989) Response patterns of purified myeloma cells to hematopoietic growth factors. Blood 73:1915–1924

    PubMed  CAS  Google Scholar 

  52. Russell RG, Watts NB, Ebetino FH et al (2008) Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 19:733–759. doi:10.1007/s00198-007-0540-8

    Article  PubMed  CAS  Google Scholar 

  53. Corey E, Brown LG, Quinn JE et al (2003) Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer. Clin Cancer Res 9:295–306

    PubMed  CAS  Google Scholar 

  54. Hiraga T, Williams PJ, Ueda A et al (2004) Zoledronic acid inhibits visceral metastases in the 4 T1/luc mouse breast cancer model. Clin Cancer Res 10:4559–4567. doi:10.1158/1078-0432.CCR-03-0325

    Article  PubMed  CAS  Google Scholar 

  55. Koto K, Horie N, Kimura S et al (2009) Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model. Cancer Lett 274:271–278. doi:10.1016/j.canlet.2008.09.026

    Article  PubMed  CAS  Google Scholar 

  56. Guenther A, Gordon S, Tiemann M et al (2010) The bisphosphonate zoledronic acid has antimyeloma activity in vivo by inhibition of protein prenylation. Int J Cancer 126:239–246. doi:10.1002/ijc.24758

    Article  PubMed  CAS  Google Scholar 

  57. Yaccoby S, Pearse RN, Johnson CL et al (2002) Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. Br J Haematol 116:278–290

    Article  PubMed  Google Scholar 

  58. Croucher PI, De Hendrik R, Perry MJ et al (2003) Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res 18:482–492

    Article  PubMed  CAS  Google Scholar 

  59. Radl J, Croese JW, Zurcher C et al (1985) Influence of treatment with APD-bisphosphonate on the bone lesions in the mouse 5 T2 multiple myeloma. Cancer 55:1030–1040

    Article  PubMed  CAS  Google Scholar 

  60. Brown HK, Holen I (2009) Anti-tumour effects of bisphosphonates–what have we learned from in vivo models? Curr Cancer Drug Targets 9:807–823

    Article  PubMed  CAS  Google Scholar 

  61. Baulch-Brown C, Molloy TJ, Yeh SL et al (2007) Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. Leuk Res 31:341–352. doi:10.1016/j.leukres.2006.07.018

    Article  PubMed  CAS  Google Scholar 

  62. Corso A, Ferretti E, Lunghi M et al (2005) Zoledronic acid down-regulates adhesion molecules of bone marrow stromal cells in multiple myeloma: a possible mechanism for its antitumor effect. Cancer 104:118–125. doi:10.1002/cncr.21104

    Article  PubMed  CAS  Google Scholar 

  63. Nefedova Y, Landowski TH, Dalton WS (2003) Bone marrow stromal-derived soluble factors and direct cell contact contribute to de novo drug resistance of myeloma cells by distinct mechanisms. Leukemia 17:1175–1182. doi:10.1038/sj.leu.2402924

    Article  PubMed  CAS  Google Scholar 

  64. Azab AK, Azab F, Blotta S et al (2009) RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood 114:619–629. doi:10.1182/blood-2009-01-199281

    Article  PubMed  CAS  Google Scholar 

  65. Denoyelle C, Hong L, Vannier JP et al (2003) New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects. Br J Cancer 88:1631–1640. doi:10.1038/sj.bjc.6600925

    Article  PubMed  CAS  Google Scholar 

  66. Karabulut B, Erten C, Gul MK et al (2009) Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells. Cell Biol Int 33:239–246. doi:10.1016/j.cellbi.2008.11.011

    Article  PubMed  CAS  Google Scholar 

  67. Rachner TD, Singh SK, Schoppet M et al (2010) Zoledronic acid induces apoptosis and changes the TRAIL/OPG ratio in breast cancer cells. Cancer Lett 287:109–116. doi:10.1016/j.canlet.2009.06.003

    Article  PubMed  CAS  Google Scholar 

  68. Berenson JR, Lichtenstein A, Porter L et al (1996) Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group N Engl J Med 334:488–493

    CAS  Google Scholar 

  69. Attal M, Harousseau JL, Leyvraz S et al (2006) Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 108:3289–3294. doi:10.1182/blood-2006-05-022962

    Article  PubMed  CAS  Google Scholar 

  70. Kondo H, Mori A (2002) Anti-tumor activity of pamidronate in human multiple myeloma. Leuk Lymphoma 43:919–921

    Article  PubMed  Google Scholar 

  71. Powles T, Paterson S, Kanis JA et al (2002) Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J Clin Oncol 20:3219–3224

    Article  PubMed  CAS  Google Scholar 

  72. Diel IJ, Jaschke A, Solomayer EF et al (2008) Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol 19:2007–2011. doi:10.1093/annonc/mdn429

    Article  PubMed  CAS  Google Scholar 

  73. Diel IJ, Solomayer EF, Costa SD et al (1998) Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 339:357–363

    Article  PubMed  CAS  Google Scholar 

  74. Gnant M, Mlineritsch B, Schippinger W et al (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679–691. doi:10.1056/NEJMoa0806285

    Article  PubMed  CAS  Google Scholar 

  75. Lipton A (2010) Should bisphosphonates be utilized in the adjuvant setting for breast cancer? Breast Cancer Res Treat 122(3):627–636

    Article  PubMed  CAS  Google Scholar 

  76. Mhaskar R, Redzepovic J, Wheatley K et al. (2010) Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev 3:CD003188. doi:10.1002/14651858.CD003188.pub2

  77. Aviles A, Nambo MJ, Neri N et al (2007) Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma. Med Oncol 24:227–230. doi:MO:24:2:227 [pii]

    Article  PubMed  CAS  Google Scholar 

  78. Vincenzi B, Santini D, Dicuonzo G et al (2005) Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients. J Interferon Cytokine Res 25:144–151. doi:10.1089/jir.2005.25.144

    Article  PubMed  CAS  Google Scholar 

  79. Cackowski FC, Anderson JL, Patrene KD et al (2010) Osteoclasts are important for bone angiogenesis. Blood 115(1):140–149

    Article  PubMed  CAS  Google Scholar 

  80. Kollet O, Dar A, Shivtiel S et al (2006) Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat Med 12:657–664. doi:10.1038/nm1417

    Article  PubMed  CAS  Google Scholar 

  81. Azab AK, Runnels JM, Pitsillides C et al (2009) CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 113:4341–4351. doi:10.1182/blood-2008-10-186668

    Article  PubMed  CAS  Google Scholar 

  82. Caccamo N, Meraviglia S, Scarpa F et al (2008) Aminobisphosphonate-activated gammadelta T cells in immunotherapy of cancer: doubts no more. Expert Opin Biol Ther 8:875–883. doi:10.1517/14712598.8.7.875

    Article  PubMed  CAS  Google Scholar 

  83. Roodman GD (2002) Role of the bone marrow microenvironment in multiple myeloma. J Bone Miner Res 17:1921–1925

    Article  PubMed  CAS  Google Scholar 

  84. Sezer O, Heider U, Zavrski I et al (2003) RANK ligand and osteoprotegerin in myeloma bone disease. Blood 101:2094–2098

    Article  PubMed  CAS  Google Scholar 

  85. Doran PM, Turner RT, Chen D et al (2004) Native osteoprotegerin gene transfer inhibits the development of murine osteolytic bone disease induced by tumor xenografts. Exp Hematol 32:351–359. doi:10.1016/j.exphem.2004.01.006

    Article  PubMed  CAS  Google Scholar 

  86. Rabin N, Kyriakou C, Coulton L et al (2007) A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer. Leukemia 21:2181–2191. doi:10.1038/sj.leu.2404814

    Article  PubMed  CAS  Google Scholar 

  87. Hamdy NA (2008) Denosumab: RANKL inhibition in the management of bone loss. Drugs Today (Barc) 44:7–21. doi:10.1358/dot.2008.44.1.1178467

    Article  CAS  Google Scholar 

  88. Body JJ, Facon T, Coleman RE et al (2006) A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 12:1221–1228

    Article  PubMed  CAS  Google Scholar 

  89. Vij R, Horvath N, Spencer A et al (2009) An open-label, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma. Am J Hematol 84:650–656. doi:10.1002/ajh.21509

    Article  PubMed  CAS  Google Scholar 

  90. Henry D, von Moos R, Vadhan-Raj S et al (2009) A double-blind, randomized study of denosumab versus zoledronic acid for the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. Eur J Cancer Suppl 7:12 Abstract.

    Google Scholar 

  91. Munshi N, Tai Y-T (2008) Antibody and other immune-based therapies for myeloma. In: Lonial S (ed) Myeloma therapy: pursuing the plasma cell. Humana Press, Totowa, NJ. doi:10.1007/978-1-59745-564-0

    Google Scholar 

  92. Ara T, Declerck YA (2010) Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 46:1223–1231. doi:10.1016/j.ejca.2010.02.026

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA

    Deborah L. Galson & Sonia D’Souza

  2. Division of Hematology Oncology, Indian University Medical Center, Indianapolis, IN, USA

    G. David Roodman M.D., Ph.D.

Authors
  1. Deborah L. Galson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonia D’Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. David Roodman M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. David Roodman M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Dana-Farber Cancer Institute, Harvard Medical School, Binney St. 44 44, Boston, 02115, Massachusetts, USA

    Nikhil C. Munshi

  2. Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Binney St. 44, Boston, 02115, Massachusetts, USA

    Kenneth C. Anderson

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Galson, D.L., D’Souza, S., Roodman, G.D. (2013). Osteoclasts: Potential Target for Blocking Microenvironmental Support of Myeloma. In: Munshi, N., Anderson, K. (eds) Advances in Biology and Therapy of Multiple Myeloma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4666-8_9

Download citation

Publish with us

Policies and ethics

Search

Navigation