M. H. Weber, D. Goltzman, P. Kostenuik, S. Rabbani, G. Singh et al., Mechanisms of tumor metastasis to bone, Crit. Rev. Eukaryot. Gene Expr, pp.10-281, 2000.

G. Eilon and G. R. Mundy, Direct resorption of bone by human breast cancer cells in vitro, Nature, vol.291, issue.5689, pp.276-726, 1978.
DOI : 10.1038/263508a0

. Boyle, Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation, Cell, vol.93, pp.165-176, 1998.

P. S. Nguyen, D. L. Ohashi, E. Lacey, W. J. Fish, J. M. Boyle et al., Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand, Nature, vol.402, pp.304-309, 1999.

K. Morinaga and . Higashio, RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis, Biochem. Biophys. Res. Commun, vol.253, pp.395-400, 1998.

D. Hughes, W. Hill, P. Pattison, P. Campbell, S. Sander et al., Osteoprotegerin: a novel secreted protein involved in the regulation of bone density, Cell, vol.89, pp.309-319, 1997.

E. Grimaud, F. Rédini, and D. Heymann, Osteoprotegerin: a new therapeutic agent for the treatment of bone disease, Drug Discovery Today, vol.6, issue.23, pp.1241-1242, 2001.
DOI : 10.1016/S1359-6446(01)02037-2

C. R. Good, R. J. O-'keefe, J. E. Puzas, E. M. Schwarz, and R. N. Rosier, Immunohistochemical study of receptor activator of nuclear factor kappa-B ligand (RANK-L) in human osteolytic bone tumors, J. Surg. Oncol, pp.79-174, 2002.

D. Rédini and . Heymann, Receptor activator of nuclear factor kappaB ligand (RANKL)

N. Giuliani, R. Bataille, C. Mancini, M. Lazzaretti, and S. Barillé, Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment, Blood, vol.98, issue.13, pp.3527-3533, 2001.
DOI : 10.1182/blood.V98.13.3527

X. Milgrom and . Mariette, RANK (receptor activator of nuclear factor-kappaB) and RANKL expression in multiple myeloma, Br. J. Haematol, vol.117, pp.86-92, 2002.

A. C. Bardy and . Zannettino, Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo, Cancer Res, vol.63, pp.5438-5445, 2003.

. Vanderkerken, Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma, Blood, vol.98, pp.3534-3540, 2001.

O. Sezer, U. Heider, C. Jakob, J. Eucker, and K. Possinger, Human Bone Marrow Myeloma Cells Express RANKL, Journal of Clinical Oncology, vol.20, issue.1, pp.353-354, 2002.
DOI : 10.1200/JCO.2002.20.1.353

J. Epstein and Y. Choi, Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression, Proc. Natl. Acad. Sci. USA 98, pp.11581-11586, 2001.

G. Hojden, S. Sammarelli, R. Barillé, V. Bataille, and . Rizzoli, Human myeloma cells stimulate the receptor activator of nuclear factor-kappaB ligand (RANKL) in T lymphocytes : a potential role in multiple myeloma bone disease, Blood, vol.100, pp.4615-4621, 2002.

H. Nielsen, A. Hjorth-hansen, A. Waage, M. Sundan, and . Borset, Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease, Blood, vol.98, pp.2269-2271, 2001.

C. R. Bekker and . Dunstan, Serum osteoprotegerin levels in healthy controls and cancer patients, Clin. Cancer Res, vol.8, pp.2306-2310, 2002.

. Sundan, Osteoprotegerin is bound, internalised and degraded by multiple myeloma cells

J. M. Yataganas, A. Goldman, and . Rahemtulla, Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma : proposal for a novel prognostic index, pp.1064-1069, 2003.

K. Nosaka, T. Miyamoto, T. Sakai, H. Mitsuya, T. Suda et al., Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kappa B ligand on adult T-cell leukemia cells, Blood, vol.99, issue.2, pp.634-640, 2002.
DOI : 10.1182/blood.V99.2.634

L. Huang, Y. Y. Cheng, L. T. Chow, M. H. Zheng, and S. M. Kumta, Tumour cells produce receptor activator of NF-kB ligand (RANKL) in skeletal metastases, J. Clin. Pathol, pp.55-877, 2002.

L. M. Demers, Bone markers in the management of patients with skeletal metastases, Cancer, vol.14, issue.S3, pp.874-879, 2003.
DOI : 10.1002/cncr.11127

S. Kitazawa and R. Kitazawa, RANK ligand is a prerequisite for cancer-associated osteolytic lesions, The Journal of Pathology, vol.103, issue.2, pp.228-236, 2002.
DOI : 10.1002/path.1199

H. R. Park, S. K. Min, H. D. Cho, D. H. Kim, H. S. Shin et al., Expression of Osteoprotegerin and RANK Ligand in Breast Cancer Bone Metastasis, Journal of Korean Medical Science, vol.18, issue.4, pp.541-546, 2003.
DOI : 10.3346/jkms.2003.18.4.541

Y. Lee, E. Schwarz, M. Davies, M. Jo, J. Gates et al., Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone, Urologic Oncology: Seminars and Original Investigations, vol.22, issue.1, pp.62-72, 2003.
DOI : 10.1016/j.urolonc.2003.12.007

B. L. Lin, C. P. Tarnowski, J. Zhang, E. Rohn, A. H. Patel et al., Bone metastatic LNCaP-derivative C4-2B prostate cancer cell line mineralizes in vitro, The Prostate, vol.16, issue.3, pp.212-221, 2001.
DOI : 10.1002/pros.1065

J. M. Brown, E. Corey, Z. D. Lee, L. D. True, T. J. Bun et al., Osteoprotegerin and rank ligand expression in prostate cancer, Urology, vol.57, issue.4, pp.611-616, 2001.
DOI : 10.1016/S0090-4295(00)01122-5

I. Holen, P. I. Croucher, F. C. Hamdy, and C. L. Eaton, Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells, Cancer Res, vol.62, pp.1619-1623, 2002.

K. Jung, M. Lein, K. Von-hösslin, B. Brux, D. Schnorr et al., Osteoprotegerin in serum as a novel marker of bone metastatic spread in prostate cancer

K. Jung, C. Stephan, A. Semjonow, M. Lein, D. Schnorr et al., Serum Osteoprotegerin and Receptor Activator of Nuclear Factor-?? B Ligand as Indicators of Disturbed Osteoclastogenesis in Patients With Prostate Cancer, The Journal of Urology, vol.170, issue.6, pp.2302-2305, 2003.
DOI : 10.1097/01.ju.0000094191.39574.cb

C. M. Shipman and P. I. Croucher, Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand and can function as a paracrine survival factor for human myeloma cells, Cancer Res, vol.63, pp.912-916, 2003.

. Findlay, Expression of osteoclast differentiation signals by stromal elements of giant cell tumors, J. Bone Min. Res, vol.15, pp.640-649, 2000.

L. Huang, J. Xu, D. J. Wood, and M. H. Zheng, Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kB in giant cell tumor of bone, Am. J. Pathol, pp.156-761, 2000.

A. Sudo, Y. Uchida, and . Ito, Spindle-shaped cells derived from giant-cell tumor of bone support differentiation of blood monocytes to osteoclast-like cells, J. Orthop. Res, vol.18, pp.647-654, 2000.

L. Huang, Y. Y. Cheng, L. T. Chow, M. H. Zheng, and S. M. Kumta, Receptor activator of NFkappaB ligand (RANKL) is expressed in chondroblastoma: possible involvement in osteoclastic giant cell recruitment, Mol. Pathol, pp.56-116, 2003.

D. Goltzman, Osteolysis and cancer, Journal of Clinical Investigation, vol.107, issue.10, pp.1219-1220, 2001.
DOI : 10.1172/JCI13073
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC209307

J. M. Chirgwin and T. A. Guise, Molecular Mechanisms of Tumor-Bone Interactions in Osteolytic Metastases, Critical Reviews?? in Eukaryotic Gene Expression, vol.10, issue.2, pp.159-178, 2000.
DOI : 10.1615/CritRevEukarGeneExpr.v10.i2.50

. Fujita, Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro, Biochem. Biophys. Res

R. Faraggiana, A. Baron, and . Teti, Melanoma cells stimulate osteoclastogenesis, c-Src expression and osteoblast cytokines, Eur. J. Cancer, vol.37, pp.629-640, 2001.

R. J. Thomas, T. A. Guise, J. J. Yin, J. Elliott, N. J. Horwood et al., Breast Cancer Cells Interact with Osteoblasts to Support Osteoclast Formation, Endocrinology, vol.140, issue.10, pp.4451-4458, 1999.
DOI : 10.1210/en.140.10.4451

A. T. Mancino, V. S. Klimberg, M. Yamamoto, S. C. Manolagas, and E. Abe, Breast Cancer Increases Osteoclastogenesis by Secreting M-CSF and Upregulating RANKL in Stromal Cells, Journal of Surgical Research, vol.100, issue.1, pp.18-24, 2001.
DOI : 10.1006/jsre.2001.6204

T. Ohshiba, C. Miyaura, M. Inada, and A. Ito, Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis, British Journal of Cancer, vol.88, issue.8
DOI : 10.1038/sj.bjc.6600858

T. J. Raymond, C. J. Janus, G. Logothetis, N. M. Karsenty, and . Navone, Prostate cancer cellsosteoblast interaction shifts expression of growth/survival-related genes in prostate cancer and reduces expression of osteoprotegerin in osteoblasts, Clin. Cancer Res, vol.9, pp.2587-2597, 2003.

E. T. Westman and . Keller, Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone, J. Clin. Invest, vol.107, pp.1235-1244, 2001.

M. Nagai, S. Kyakumoto, and N. Sato, Cancer Cells Responsible for Humoral Hypercalcemia Express mRNA Encoding a Secreted Form of ODF/TRANCE That Induces Osteoclast Formation, Biochemical and Biophysical Research Communications, vol.269, issue.2, pp.269-532, 2000.
DOI : 10.1006/bbrc.2000.2314

T. Michigami, M. Ihara-watanabe, M. Yamazaki, and K. Ozono, Receptor activator of nuclear factor kappaB ligand (RANKL) is a key molecule of osteoclast formation for bone metastasis in a newly developed model of human neuroblastoma, Cancer Res, pp.61-1637, 2001.

T. A. Guise and J. M. Chirgwin, Transforming Growth Factor-Beta in Osteolytic Breast Cancer Bone Metastases, Clinical Orthopaedics and Related Research, vol.415, pp.415-447, 2003.
DOI : 10.1097/01.blo.0000093055.96273.69

B. Blum, J. Moseley, L. Miller, K. Richelsoph, and W. Haggard, Measurement of bone morphogenetic proteins and other growth factors in demineralized bone matrix, Orthopedics, vol.27, pp.161-165, 2004.

J. Thiéry, B. Perdereau, R. Gongora, G. Gongora, and A. Mazabraud, Un modèle experimental d'ostéosarcome chez le rat. II L'ostéosarcome greffable du rat, Sem. Hôp. Paris, vol.58, pp.1686-1689, 1982.

N. Udagawa, T. Takahashi, and . Suda, Osteoclast differentiation factor is a ligand for osteoprotegerin /osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL, Proc. Natl. Acad. Sci. U S A, pp.95-3597, 1998.

K. Higashio, M. Motoyoshi, N. Yamamoto, and . Nagata, Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy, Bone, vol.23, pp.495-498, 1998.

D. L. Qi, C. R. Lacey, and . Dunstan, Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypercalcemia of malignancy, Cancer Res, vol.60, pp.783-787, 2000.

D. R. Clohisy, M. L. Ramnaraine, S. Scully, M. Qi, G. Van et al., Osteoprotegerin inhibits tumor-induced osteoclastogenesis and bone tumor growth in osteopetrotic mice, Journal of Orthopaedic Research, vol.103, issue.6, pp.967-976, 2000.
DOI : 10.1002/jor.1100180617

P. I. Croucher, C. M. Shipman, B. Van-camp, and K. Vanderkerken, Bisphosphonates and osteoprotegerin as inhibitors of myeloma bone disease, Cancer, vol.98, issue.S3, pp.818-824, 2003.
DOI : 10.1002/cncr.11125

K. Vanderkerken, E. De-leenheer, C. Shipman, K. Asosingh, A. Willems et al., Recombinant osteoprotegerin decreases tumor burden and increases survival in a murine model of multiple myeloma, Cancer Res, vol.63, pp.287-289, 2003.

Y. Hatano, A. Ogawa, and . Ochiai, Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice, Cancer Res, vol.63, pp.2096-2102, 2003.

M. L. O-'keefe, D. R. Ramnaraine, P. W. Clohisy, and . Mantyh, Osteoprotegerin blocks bone cancerinduced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord, Nat. Med, vol.6, pp.521-528, 2000.

P. W. Clohisy and . Mantyh, Osteoprotegerin diminishes advanced bone cancer pain, Cancer Res, vol.61, pp.4038-4047, 2001.

S. Zannettino, D. M. Hay, and . Findlay, Osteoprotegerin inhibits osteoclast formation and bone resorbing activity in giant cell tumors of bone, Bone, vol.28, pp.370-377, 2001.

P. J. Dunstan and . Bekker, A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases, Cancer, vol.97, pp.887-892, 2003.

J. Zhang, J. Dai, Z. Yao, Y. Lu, W. Dougall et al., Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone, Cancer Res, vol.63, pp.7883-7890, 2003.

E. M. Sordillo and R. N. Pearse, RANK-Fc: A therapeutic antagonist for RANK-L in myeloma, Cancer, vol.248, issue.S3, pp.802-812, 2003.
DOI : 10.1002/cncr.11134

B. O. Oyajobi and G. R. Mundy, Receptor activator of NF-?B ligand, macrophage inflammatory protein-1?, and the proteasome, Cancer, vol.17, issue.S3, pp.813-817, 2003.
DOI : 10.1002/cncr.11133

X. Cheng, M. Kinosaki, M. Takami, Y. Choi, H. Zhang et al., Disabling of RANK receptor complex by novel osteoprotegerin like peptidomimetics restores bone loss in-vivo