Skip to main content
Top
Published in: Journal of Bone and Mineral Metabolism 3/2010

01-05-2010 | Review Article

Targeting the bone microenvironment in multiple myeloma

Author: G. David Roodman

Published in: Journal of Bone and Mineral Metabolism | Issue 3/2010

Login to get access

Abstract

Multiple myeloma (MM) is a plasma cell malignancy characterized by the frequent development of osteolytic lesions, osteopenia, pathological fractures, and/or severe bone pain. In the past few years several potential factors involved in this process have been identified and, with the increased knowledge of the signaling pathways involved in the regulation of normal osteoblast and osteoclast function, have provided us with a better understanding of the contributions of the marrow microenvironment to MM bone disease. These studies have identified several potential novel targets for treating MM bone disease in addition to the current standard treatment of bisphosphonates. In this article, we discuss several potential targets for treating MM bone disease as well as novel therapies that are in clinical trials for these patients.
Literature
1.
go back to reference Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton LJ 3rd (2004) Incidence of multiple myeloma in Olmsted County, Minnesota: trend over 6 decades. Cancer (Phila) 101:2667–2674CrossRef Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton LJ 3rd (2004) Incidence of multiple myeloma in Olmsted County, Minnesota: trend over 6 decades. Cancer (Phila) 101:2667–2674CrossRef
2.
go back to reference Phekoo KJ, Schey SA, Richards MA, Bevan DH, Bell S, Gillett D, Moller H (2004) A population study to define the incidence and survival of multiple myeloma in a National Health Service Region in UK. Br J Haematol 127:299–304CrossRefPubMed Phekoo KJ, Schey SA, Richards MA, Bevan DH, Bell S, Gillett D, Moller H (2004) A population study to define the incidence and survival of multiple myeloma in a National Health Service Region in UK. Br J Haematol 127:299–304CrossRefPubMed
3.
go back to reference American Cancer Society (2009) Cancer facts and figures. American Cancer Society, Atlanta, GA, pp 1–69 American Cancer Society (2009) Cancer facts and figures. American Cancer Society, Atlanta, GA, pp 1–69
5.
go back to reference Melton LJ 3rd, Kyle RA, Achenbach SJ, Oberg AL, Rajkumar SV (2005) Fracture risk with multiple myeloma: a population-based study. J Bone Miner Res 20:487–493CrossRefPubMed Melton LJ 3rd, Kyle RA, Achenbach SJ, Oberg AL, Rajkumar SV (2005) Fracture risk with multiple myeloma: a population-based study. J Bone Miner Res 20:487–493CrossRefPubMed
6.
go back to reference Taube T, Beneton MN, McCloskey EV, Rogers S, Greaves M, Kanis JA (1992) Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption. Eur J Haematol 49:192–198PubMed Taube T, Beneton MN, McCloskey EV, Rogers S, Greaves M, Kanis JA (1992) Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption. Eur J Haematol 49:192–198PubMed
8.
go back to reference Gordon S, Helfrich MH, Sati HI, Greaves M, Ralston SH, Culligan DJ, Soutar RL, Rogers MJ (2002) Pamidronate causes apoptosis of plasma cells in vivo in patients with multiple myeloma. Br J Haematol 119:475–483CrossRefPubMed Gordon S, Helfrich MH, Sati HI, Greaves M, Ralston SH, Culligan DJ, Soutar RL, Rogers MJ (2002) Pamidronate causes apoptosis of plasma cells in vivo in patients with multiple myeloma. Br J Haematol 119:475–483CrossRefPubMed
9.
go back to reference Vinholes JJ, Purohit OP, Abbey ME, Eastell R, Coleman RE (1997) Relationships between biochemical and symptomatic response in a double-blind randomised trial of pamidronate for metastatic bone disease. Ann Oncol 8:1243–1250CrossRefPubMed Vinholes JJ, Purohit OP, Abbey ME, Eastell R, Coleman RE (1997) Relationships between biochemical and symptomatic response in a double-blind randomised trial of pamidronate for metastatic bone disease. Ann Oncol 8:1243–1250CrossRefPubMed
10.
go back to reference Petcu EB, Schug SA, Smith H (2002) Clinical evaluation of onset of analgesia using intravenous pamidronate in metastatic bone pain. J Pain Symptom Manage 24:281–284CrossRefPubMed Petcu EB, Schug SA, Smith H (2002) Clinical evaluation of onset of analgesia using intravenous pamidronate in metastatic bone pain. J Pain Symptom Manage 24:281–284CrossRefPubMed
11.
go back to reference Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, Kuhn JA, Dratch AD, D’Agati VD (2001) Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 12:1164–1172PubMed Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, Kuhn JA, Dratch AD, D’Agati VD (2001) Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 12:1164–1172PubMed
12.
go back to reference Desikan R, Veksler Y, Raza S, Stokes B, Sabir T, Li ZJ, Jagannath S (2002) Nephrotic proteinuria associated with high-dose pamidronate in multiple myeloma. Br J Haematol 119:496–499CrossRefPubMed Desikan R, Veksler Y, Raza S, Stokes B, Sabir T, Li ZJ, Jagannath S (2002) Nephrotic proteinuria associated with high-dose pamidronate in multiple myeloma. Br J Haematol 119:496–499CrossRefPubMed
13.
go back to reference Gunn WG, Conley A, Deininger L, Olson SD, Prockop DJ, Gregory CA (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 24:986–991CrossRefPubMed Gunn WG, Conley A, Deininger L, Olson SD, Prockop DJ, Gregory CA (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 24:986–991CrossRefPubMed
14.
go back to reference Choi SJ, Cruz JC, Craig F, Chung H, Devlin RD, Roodman GD, Alsina M (2000) Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood 96:671–675PubMed Choi SJ, Cruz JC, Craig F, Chung H, Devlin RD, Roodman GD, Alsina M (2000) Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood 96:671–675PubMed
15.
go back to reference 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 32:685–691CrossRefPubMed 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 32:685–691CrossRefPubMed
16.
go back to reference Lee JW, Chung HY, Ehrlich LA, Jelinek DF, Callander NS, Roodman GD, Choi SJ (2004) IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood 103:2308–2315CrossRefPubMed Lee JW, Chung HY, Ehrlich LA, Jelinek DF, Callander NS, Roodman GD, Choi SJ (2004) IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood 103:2308–2315CrossRefPubMed
17.
go back to reference Ehrlich LA, Roodman GD (2005) The role of immune cells and inflammatory cytokines in Paget’s disease and multiple myeloma. Immunol Rev 208:252–266CrossRefPubMed Ehrlich LA, Roodman GD (2005) The role of immune cells and inflammatory cytokines in Paget’s disease and multiple myeloma. Immunol Rev 208:252–266CrossRefPubMed
18.
go back to reference Sezer O, Heider U, Jakob C, Zavrski I, Eucker J, Possinger K, Sers C, Krenn V (2002) Immunocytochemistry reveals RANKL expression of myeloma cells. Blood 99:4646–4647CrossRefPubMed Sezer O, Heider U, Jakob C, Zavrski I, Eucker J, Possinger K, Sers C, Krenn V (2002) Immunocytochemistry reveals RANKL expression of myeloma cells. Blood 99:4646–4647CrossRefPubMed
19.
go back to reference Giuliani N, Colla S, Sala R, Moroni M, Lazzaretti M, La Monica S, Bonomini S, Hojden M, Sammarelli G, Barille S, Bataille R, Rizzoli V (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 100:4615–4621CrossRefPubMed Giuliani N, Colla S, Sala R, Moroni M, Lazzaretti M, La Monica S, Bonomini S, Hojden M, Sammarelli G, Barille S, Bataille R, Rizzoli V (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 100:4615–4621CrossRefPubMed
20.
go back to reference Pearse RN, Sordillo EM, Yaccoby S, Wong BR, Liau DF, Colman N, Michaeli J, Epstein J, Choi Y (2001) Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci USA 98:11581–11586CrossRefPubMed Pearse RN, Sordillo EM, Yaccoby S, Wong BR, Liau DF, Colman N, Michaeli J, Epstein J, Choi Y (2001) Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci USA 98:11581–11586CrossRefPubMed
21.
go back to reference Menu E, Asosingh K, Van Riet I, Croucher P, Van Camp B, Vanderkerken K (2004) Myeloma cells (5TMM) and their interactions with the marrow microenvironment. Blood Cells Mol Dis 33:111–119CrossRefPubMed Menu E, Asosingh K, Van Riet I, Croucher P, Van Camp B, Vanderkerken K (2004) Myeloma cells (5TMM) and their interactions with the marrow microenvironment. Blood Cells Mol Dis 33:111–119CrossRefPubMed
22.
go back to reference Epstein J, Yaccoby S (2005) The SCID-hu myeloma model. Methods Mol Med 113:183–190PubMed Epstein J, Yaccoby S (2005) The SCID-hu myeloma model. Methods Mol Med 113:183–190PubMed
23.
go back to reference Oba Y, Lee JW, Ehrlich LA, Chung HY, Jelinek DF, Callander NS, Horuk R, Choi SJ, Roodman GD (2005) MIP-1alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells. Exp Hematol 33:272–278CrossRefPubMed Oba Y, Lee JW, Ehrlich LA, Chung HY, Jelinek DF, Callander NS, Horuk R, Choi SJ, Roodman GD (2005) MIP-1alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells. Exp Hematol 33:272–278CrossRefPubMed
24.
go back to reference Vallet S, Raje N, Ishitsuka K, Hideshima T, Podar K, Chhetri S, Pozzi S, Breitkreutz I, Kiziltepe T, Yasui H, Ocio EM, Shiraishi N, Jin J, Okawa Y, Ikeda H, Mukherjee S, Vaghela N, Cirstea D, Ladetto M, Boccadoro M, Anderson KC (2007) MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. Blood 110:3744–3752CrossRefPubMed Vallet S, Raje N, Ishitsuka K, Hideshima T, Podar K, Chhetri S, Pozzi S, Breitkreutz I, Kiziltepe T, Yasui H, Ocio EM, Shiraishi N, Jin J, Okawa Y, Ikeda H, Mukherjee S, Vaghela N, Cirstea D, Ladetto M, Boccadoro M, Anderson KC (2007) MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. Blood 110:3744–3752CrossRefPubMed
25.
go back to reference Menu E, De Leenheer E, De Raeve H, Coulton L, Imanishi T, Miyashita K, Van Valckenborgh E, Van Riet I, Van Camp B, Horuk R, Croucher P, Vanderkerken K (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 23:291–300CrossRefPubMed Menu E, De Leenheer E, De Raeve H, Coulton L, Imanishi T, Miyashita K, Van Valckenborgh E, Van Riet I, Van Camp B, Horuk R, Croucher P, Vanderkerken K (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 23:291–300CrossRefPubMed
26.
go back to reference Merico F, Bergui L, Gregoretti MG, Ghia P, Aimo G, Lindley IJ, Caligaris-Cappio F (1993) Cytokines involved in the progression of multiple myeloma. Clin Exp Immunol 92:27–31PubMedCrossRef Merico F, Bergui L, Gregoretti MG, Ghia P, Aimo G, Lindley IJ, Caligaris-Cappio F (1993) Cytokines involved in the progression of multiple myeloma. Clin Exp Immunol 92:27–31PubMedCrossRef
27.
go back to reference Barton BE, Mayer R (1989) IL-3 induces differentiation of bone marrow precursor cells to osteoclast-like cells. J Immunol 143:3211–3216PubMed Barton BE, Mayer R (1989) IL-3 induces differentiation of bone marrow precursor cells to osteoclast-like cells. J Immunol 143:3211–3216PubMed
28.
go back to reference Solary E, Guiguet M, Zeller V, Casasnovas RO, Caillot D, Chavanet P, Guy H, Mack G (1992) Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma. Am J Hematol 39:163–171CrossRefPubMed Solary E, Guiguet M, Zeller V, Casasnovas RO, Caillot D, Chavanet P, Guy H, Mack G (1992) Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma. Am J Hematol 39:163–171CrossRefPubMed
29.
go back to reference Sati HI, Apperley JF, Greaves M, Lawry J, Gooding R, Russell RG, Croucher PI (1998) Interleukin-6 is expressed by plasma cells from patients with multiple myeloma and monoclonal gammopathy of undetermined significance. Br J Haematol 101:287–295CrossRefPubMed Sati HI, Apperley JF, Greaves M, Lawry J, Gooding R, Russell RG, Croucher PI (1998) Interleukin-6 is expressed by plasma cells from patients with multiple myeloma and monoclonal gammopathy of undetermined significance. Br J Haematol 101:287–295CrossRefPubMed
30.
go back to reference Abildgaard N, Glerup H, Rungby J, Bendix-Hansen K, Kassem M, Brixen K, Heickendorff L, Nielsen JL, Eriksen EF (2000) Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. Eur J Haematol 64:121–129CrossRefPubMed Abildgaard N, Glerup H, Rungby J, Bendix-Hansen K, Kassem M, Brixen K, Heickendorff L, Nielsen JL, Eriksen EF (2000) Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. Eur J Haematol 64:121–129CrossRefPubMed
31.
go back to reference Karadag A, Oyajobi BO, Apperley JF, Russell RG, Croucher PI (2000) Human myeloma cells promote the production of interleukin 6 by primary human osteoblasts. Br J Haematol 108:383–390CrossRefPubMed Karadag A, Oyajobi BO, Apperley JF, Russell RG, Croucher PI (2000) Human myeloma cells promote the production of interleukin 6 by primary human osteoblasts. Br J Haematol 108:383–390CrossRefPubMed
32.
go back to reference Abe M, Hiura K, Wilde J, Shioyasono A, Moriyama K, Hashimoto T, Kido S, Oshima T, Shibata H, Ozaki S, Inoue D, Matsumoto T (2004) Osteoclasts enhance myeloma cell growth and survival via cell–cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood 104:2484–2491CrossRefPubMed Abe M, Hiura K, Wilde J, Shioyasono A, Moriyama K, Hashimoto T, Kido S, Oshima T, Shibata H, Ozaki S, Inoue D, Matsumoto T (2004) Osteoclasts enhance myeloma cell growth and survival via cell–cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood 104:2484–2491CrossRefPubMed
33.
go back to reference Anderson KC, Jones RM, Morimoto C, Leavitt P, Barut BA (1989) Response patterns of purified myeloma cells to hematopoietic growth factors. Blood 73:1915–1924PubMed Anderson KC, Jones RM, Morimoto C, Leavitt P, Barut BA (1989) Response patterns of purified myeloma cells to hematopoietic growth factors. Blood 73:1915–1924PubMed
34.
go back to reference Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S, Rizzoli V, Roodman GD, Giuliani N (2005) IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood 106:1407–1414CrossRefPubMed Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S, Rizzoli V, Roodman GD, Giuliani N (2005) IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood 106:1407–1414CrossRefPubMed
35.
go back to reference Giuliani N, Colla S, Morandi F, Lazzaretti M, Sala R, Bonomini S, Grano M, Colucci S, Svaldi M, Rizzoli V (2005) Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 106:2472–2483CrossRefPubMed Giuliani N, Colla S, Morandi F, Lazzaretti M, Sala R, Bonomini S, Grano M, Colucci S, Svaldi M, Rizzoli V (2005) Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 106:2472–2483CrossRefPubMed
36.
go back to reference Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T (2005) Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 106:3160–3165CrossRefPubMed Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T (2005) Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 106:3160–3165CrossRefPubMed
37.
go back to reference Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494CrossRefPubMed Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494CrossRefPubMed
38.
go back to reference Canalis E, Deregowski V, Pereira RC, Gazzerro E (2005) Signals that determine the fate of osteoblastic cells. J Endocrinol Invest 28:3–7PubMed Canalis E, Deregowski V, Pereira RC, Gazzerro E (2005) Signals that determine the fate of osteoblastic cells. J Endocrinol Invest 28:3–7PubMed
39.
go back to reference Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene (Amst) 341:19–39 Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene (Amst) 341:19–39
40.
go back to reference Bain G, Muller T, Wang X, Papkoff J (2003) Activated beta-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction. Biochem Biophys Res Commun 301:84–91CrossRefPubMed Bain G, Muller T, Wang X, Papkoff J (2003) Activated beta-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction. Biochem Biophys Res Commun 301:84–91CrossRefPubMed
41.
go back to reference Qiang YW, Chen Y, Stephens O, Brown N, Chen B, Epstein J, Barlogie B, Shaughnessy JD Jr (2008) Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood 112:196–207CrossRefPubMed Qiang YW, Chen Y, Stephens O, Brown N, Chen B, Epstein J, Barlogie B, Shaughnessy JD Jr (2008) Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood 112:196–207CrossRefPubMed
42.
go back to reference Politou MC, Heath DJ, Rahemtulla A, Szydlo R, Anagnostopoulos A, Dimopoulos MA, Croucher PI, Terpos E (2006) Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer 119:1728–1731CrossRefPubMed Politou MC, Heath DJ, Rahemtulla A, Szydlo R, Anagnostopoulos A, Dimopoulos MA, Croucher PI, Terpos E (2006) Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer 119:1728–1731CrossRefPubMed
43.
go back to reference Kaiser M, Mieth M, Liebisch P, Oberlander R, Rademacher J, Jakob C, Kleeberg L, Fleissner C, Braendle E, Peters M, Stover D, Sezer O, Heider U (2008) Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol 80:490–494CrossRefPubMed Kaiser M, Mieth M, Liebisch P, Oberlander R, Rademacher J, Jakob C, Kleeberg L, Fleissner C, Braendle E, Peters M, Stover D, Sezer O, Heider U (2008) Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol 80:490–494CrossRefPubMed
44.
go back to reference Zangari M, Esseltine D, Cavallo F, Neuwirth R, Elice F, Burns MJ, Yaccoby S, Richardson P, Sonneveld P, Tricot G (2007) Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients. Am J Hematol 82:831–833CrossRefPubMed Zangari M, Esseltine D, Cavallo F, Neuwirth R, Elice F, Burns MJ, Yaccoby S, Richardson P, Sonneveld P, Tricot G (2007) Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients. Am J Hematol 82:831–833CrossRefPubMed
45.
go back to reference Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T (2004) Myeloma cells suppress osteoblast differentiation by secreting a soluble wnt inhibitor, sFRP-2. American Society of Hematology, San Diego, CA (abstract 2356) Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T (2004) Myeloma cells suppress osteoblast differentiation by secreting a soluble wnt inhibitor, sFRP-2. American Society of Hematology, San Diego, CA (abstract 2356)
46.
go back to reference De Vos J, Couderc G, Tarte K, Jourdan M, Requirand G, Delteil MC, Rossi JF, Mechti N, Klein B (2001) Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays. Blood 98:771–780CrossRefPubMed De Vos J, Couderc G, Tarte K, Jourdan M, Requirand G, Delteil MC, Rossi JF, Mechti N, Klein B (2001) Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays. Blood 98:771–780CrossRefPubMed
47.
go back to reference Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Donofrio G, Bonomini S, Sala R, Mangoni M, Rizzoli V (2007) Production of Wnt inhibitors by myeloma cells: potential effects on canonical Wnt pathway in the bone microenvironment. Cancer Res 67:7665–7674CrossRefPubMed Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Donofrio G, Bonomini S, Sala R, Mangoni M, Rizzoli V (2007) Production of Wnt inhibitors by myeloma cells: potential effects on canonical Wnt pathway in the bone microenvironment. Cancer Res 67:7665–7674CrossRefPubMed
48.
go back to reference Davies FE, Dring AM, Li C, Rawstron AC, Shammas MA, O’Connor SM, Fenton JA, Hideshima T, Chauhan D, Tai IT, Robinson E, Auclair D, Rees K, Gonzalez D, Ashcroft AJ, Dasgupta R, Mitsiades C, Mitsiades N, Chen LB, Wong WH, Munshi NC, Morgan GJ, Anderson KC (2003) Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood 102:4504–4511CrossRefPubMed Davies FE, Dring AM, Li C, Rawstron AC, Shammas MA, O’Connor SM, Fenton JA, Hideshima T, Chauhan D, Tai IT, Robinson E, Auclair D, Rees K, Gonzalez D, Ashcroft AJ, Dasgupta R, Mitsiades C, Mitsiades N, Chen LB, Wong WH, Munshi NC, Morgan GJ, Anderson KC (2003) Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood 102:4504–4511CrossRefPubMed
49.
go back to reference Weitzmann MN, Roggia C, Toraldo G, Weitzmann L, Pacifici R (2002) Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J Clin Invest 110:1643–1650PubMed Weitzmann MN, Roggia C, Toraldo G, Weitzmann L, Pacifici R (2002) Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J Clin Invest 110:1643–1650PubMed
50.
go back to reference Giuliani N, Rizzoli V (2007) Myeloma cells and bone marrow osteoblast interactions: role in the development of osteolytic lesions in multiple myeloma. Leuk Lymphoma 48:2323–2329CrossRefPubMed Giuliani N, Rizzoli V (2007) Myeloma cells and bone marrow osteoblast interactions: role in the development of osteolytic lesions in multiple myeloma. Leuk Lymphoma 48:2323–2329CrossRefPubMed
51.
go back to reference Body JJ, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, Holloway D, Peterson MC, Bekker PJ (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 12:1221–1228CrossRefPubMed Body JJ, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, Holloway D, Peterson MC, Bekker PJ (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 12:1221–1228CrossRefPubMed
52.
go back to reference Vij R, Horvath N, Spencer A, Taylor K, Saroj V, Smith J, Qian Y, Jun S (2007) An open label phase 2 trial of Denosumab in the treatment of relapsed or plateau-phase myeloma. Blood 118:1054A Vij R, Horvath N, Spencer A, Taylor K, Saroj V, Smith J, Qian Y, Jun S (2007) An open label phase 2 trial of Denosumab in the treatment of relapsed or plateau-phase myeloma. Blood 118:1054A
53.
go back to reference Henry D, von Moos R, Vadhan-Raj S, Hungria V, Spencer A, Hirsh V, Wang J, Jun S, Yeh H, Dansey R (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)CrossRef Henry D, von Moos R, Vadhan-Raj S, Hungria V, Spencer A, Hirsh V, Wang J, Jun S, Yeh H, Dansey R (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)CrossRef
54.
go back to reference von Metzler I, Krebbel H, Hecht M, Manz RA, Fleissner C, Mieth M, Kaiser M, Jakob C, Sterz J, Kleeberg L, Heider U, Sezer O (2007) Bortezomib inhibits human osteoclastogenesis. Leukemia 21:2025–2034CrossRef von Metzler I, Krebbel H, Hecht M, Manz RA, Fleissner C, Mieth M, Kaiser M, Jakob C, Sterz J, Kleeberg L, Heider U, Sezer O (2007) Bortezomib inhibits human osteoclastogenesis. Leukemia 21:2025–2034CrossRef
55.
go back to reference Terpos E, Sezer O, Croucher P, Dimopoulos MA (2007) Myeloma bone disease and proteasome inhibition therapies. Blood 110:1098–1104CrossRefPubMed Terpos E, Sezer O, Croucher P, Dimopoulos MA (2007) Myeloma bone disease and proteasome inhibition therapies. Blood 110:1098–1104CrossRefPubMed
56.
go back to reference Ozaki S, Tanaka O, Fujii S, Shigekiyo Y, Miki H, Choraku M, Kagawa K, Asano J, Takeuchi K, Kitazoe K, Hashimoto T, Abe M, Matsumoto T (2007) Therapy with bortezomib plus dexamethasone induces osteoblast activation in responsive patients with multiple myeloma. Int J Hematol 86:180–185CrossRefPubMed Ozaki S, Tanaka O, Fujii S, Shigekiyo Y, Miki H, Choraku M, Kagawa K, Asano J, Takeuchi K, Kitazoe K, Hashimoto T, Abe M, Matsumoto T (2007) Therapy with bortezomib plus dexamethasone induces osteoblast activation in responsive patients with multiple myeloma. Int J Hematol 86:180–185CrossRefPubMed
57.
go back to reference Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Bonomini S, Crugnola M, Mancini C, Martella E, Ferrari L, Tabilio A, Rizzoli V (2007) The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 110:334–338CrossRefPubMed Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Bonomini S, Crugnola M, Mancini C, Martella E, Ferrari L, Tabilio A, Rizzoli V (2007) The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 110:334–338CrossRefPubMed
Metadata
Title
Targeting the bone microenvironment in multiple myeloma
Author
G. David Roodman
Publication date
01-05-2010
Publisher
Springer Japan
Published in
Journal of Bone and Mineral Metabolism / Issue 3/2010
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-009-0154-7

Other articles of this Issue 3/2010

Journal of Bone and Mineral Metabolism 3/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.