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Tumors of the Chest pp 551–562Cite as

Pathophysiology and Management of Bone Metastases in Lung Cancer

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48.5 Conclusions and Future Perspectives

Bone metastases are among the most difficult problems to manage in patients with lung cancer. The identification of molecular mechanisms responsible for the tropism of some lung cancer cells to the bones, using gene arrays and proteomics, could help in the earlier detection of bone metastases in these patients. Furthermore, the better understanding of the interactions between lung cancer cells and the bone marrow microenvironment that mediate the process of bone destruction should result in the development of therapeutic agents, such as recombinant human OPG, RANK-Fc, and anti-PTHrP, to treat and possibly prevent this devastating complication of lung cancer.

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References

  1. Quint LE, Francis IR, Wahl RL, Gross BH. Imaging of lung cancer. In: Pass HI, Mitchell JB, Johnson DH, Turrisi AT (eds) Lung Cancer: Principles and Practice. Philadelphia: Lippincott-Raven, 1996:437.

    Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94:153.

    Article  PubMed  CAS  Google Scholar 

  3. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002; 2:584.

    Article  PubMed  CAS  Google Scholar 

  4. Coleman R. Skeletal complications of malignancy. Cancer 1997; 80:1588.

    Article  PubMed  CAS  Google Scholar 

  5. Bloomfield D. Should bisphosphonates be part of standard therapy of patients with multiple myeloma or bone metastases from other cancers? An evidence-based review. J Clin Oncol 1998; 16:1218.

    PubMed  CAS  Google Scholar 

  6. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997; 69:1.

    Article  PubMed  CAS  Google Scholar 

  7. Delea T, Langer C, McKiernan J, et al. The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer. Oncology 2004; 67:390.

    Article  PubMed  Google Scholar 

  8. Mundy GR. Cellular and molecular regulation of bone turnover. Bone 1999; 24(5 suppl):35S.

    Article  PubMed  CAS  Google Scholar 

  9. Christenson RH. Biochemical markers of bone metabolism: an overview. Clin Biochem 1997; 30:573.

    Article  PubMed  CAS  Google Scholar 

  10. Hodge JM, Kirkland MA, Aitken CJ, et al. Osteoclastic potential of human CFU-GM: biphasic effect of GM-CSF. J Bone Miner Res 2004; 19:190.

    Article  PubMed  CAS  Google Scholar 

  11. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004; 350:1655.

    Article  PubMed  CAS  Google Scholar 

  12. Goldring SR. Inflammatory mediators as essential elements in bone remodelling. Calcif Tissue Int 2003; 73:97.

    Article  PubMed  CAS  Google Scholar 

  13. Itoh K, Udagawa N, Matsuzaki K, et al. Importance of membrane-or matrix-associated forms of M-CSF and RANKL/ODF in osteoclastogenesis supported by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors. J Bone Miner Res 2000; 15:1766.

    Article  PubMed  CAS  Google Scholar 

  14. Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 1999; 397:315.

    Article  PubMed  CAS  Google Scholar 

  15. Teitelbaum SL. Bone resorption by osteoclasts. Science 2000; 289:1504.

    Article  PubMed  CAS  Google Scholar 

  16. Horowitz MC, Xi Y, Wilson K, Kacena MA. Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev 2001; 12:9.

    Article  PubMed  CAS  Google Scholar 

  17. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89:309.

    Article  PubMed  CAS  Google Scholar 

  18. Morinaga T, Nakagawa N, Yasuda H, Tsuda E, Higashio K. Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor. Eur J Biochem 1998; 254:685.

    Article  PubMed  CAS  Google Scholar 

  19. Kim N, Odgren PR, Kim DK, Marks SC Jr, Choi Y. Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene. Proc Natl Acad Sci U S A 2000; 97:10905.

    Article  PubMed  CAS  Google Scholar 

  20. Bucay N, Sarosi I, Dunstan CR, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998; 12:1260.

    PubMed  CAS  Google Scholar 

  21. Body JJ, Greipp P, Coleman RE, et al. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer 2003; 97(3 suppl):887.

    Article  PubMed  Google Scholar 

  22. Vanderkerken K, Asosingh K, Croucher P, Van Camp B. Multiple myeloma biology: lessons from the 5TMM models. Immunol Rev 2003; 194:196.

    Article  PubMed  CAS  Google Scholar 

  23. Stein GS, Lian JB. Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev 1993; 14:424.

    Article  PubMed  CAS  Google Scholar 

  24. Ahdjoudj S, Fromigue O, Marie PJ. Plasticity and regulation of human bone marrow stromal osteoprogenitor cells: potential implication in the treatment of age-related bone loss. Histol Histopathol 2004; 19:151.

    PubMed  CAS  Google Scholar 

  25. Abe E, Yamamoto M, Taguchi Y, et al. Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res 2000; 15:663.

    Article  PubMed  CAS  Google Scholar 

  26. Power RA, Iwaniec UT, Magee KA, Mitova-Caneva NG, Wronski TJ. Basic fibroblast growth factor has rapid bone anabolic effects in ovariectomized rats. Osteoporos Int 2004; 15:716.

    Article  PubMed  CAS  Google Scholar 

  27. Cornish J, Grey A, Callon KE, et al. Shared pathways of osteoblast mitogenesis induced by amylin, adrenomedullin, and IGF-1. Biochem Biophys Res Commun 2004; 318:240.

    Article  PubMed  CAS  Google Scholar 

  28. Ortiz CO, Chen BK, Bale LK, Overgaard MT, Oxvig C, Conover CA. Transforming growth factor-beta regulation of the insulin-like growth factor binding protein-4 protease system in cultured human osteoblasts. J Bone Miner Res 2003; 18:1066.

    Article  PubMed  CAS  Google Scholar 

  29. Chaudhary LR, Hofmeister AM, Hruska KA. Differential growth factor control of bone formation through osteo-progenitor differentiation. Bone 2004; 34:402.

    Article  PubMed  CAS  Google Scholar 

  30. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889; 1:571.

    Article  Google Scholar 

  31. Kahn D, Weiner GJ, Ben-Haim S, et al. Positron emission tomographic measurement of bone marrow blood flow to the pelvis and lumbar vertebrae in young normal adults. Blood 1994; 83:958.

    PubMed  CAS  Google Scholar 

  32. van der Pluijm G, Sijmons B, Vloedgraven H, Deckers M, Papapoulos S, Lowik C. Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases. J Bone Miner Res 2001; 16:1077.

    Article  PubMed  Google Scholar 

  33. Hauschka PV, Mavrakos AE, Iafrati MD, Doleman SE, Klagsbrun M. Growth factors in bone matrix: isolation of multiple types by affinity chromatography on heparin-Sepharose. J Biol Chem 1986; 261:12665.

    PubMed  CAS  Google Scholar 

  34. Liotta LA, Kohn E. Cancer invasion and metastases. JAMA 1990; 263:1123.

    Article  PubMed  CAS  Google Scholar 

  35. Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature 2001; 411:375.

    Article  PubMed  CAS  Google Scholar 

  36. Hendrix RW, Rogers LF, Davis TM Jr. Cortical bone metastases. Radiology 1991; 181:409.

    PubMed  CAS  Google Scholar 

  37. Yin JJ, Pollock CB, Kelly K. Mechanisms of cancer metastasis to the bone. Cell Res 2005; 15:57.

    Article  PubMed  CAS  Google Scholar 

  38. Chirgwin JM, Guise TA. Molecular mechanisms of tumor-bone interactions in osteolytic metastases. Crit Rev Eukaryot Gene Expr 2000; 10:159.

    PubMed  CAS  Google Scholar 

  39. Powell GJ, Southby J, Danks JA, et al. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 1991; 51:3059.

    PubMed  CAS  Google Scholar 

  40. Miki T, Yano S, Hanibuchi M, Kanematsu T, Muguruma H, Sone S. Parathyroid hormone-related protein (PTHrP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice. Int J Can cer 2004; 108:511.

    CAS  Google Scholar 

  41. Hastings RH. Parathyroid hormone-related protein and lung biology. Respir Physiol Neurobiol 2004; 142:95.

    Article  PubMed  CAS  Google Scholar 

  42. Moseley JM, Kubota M, Diefenbach-Jagger H, et al. Parathyroid hormone-related protein purified from a human lung cancer cell line. Proc Natl Acad Sci U S A 1987; 84:5052.

    Article  Google Scholar 

  43. Brandt DW, Burton DW, Gazdar AF, Oie HE, Deftos LJ. All major lung cancer cell types produce parathyroid hormone-like protein: heterogeneity assessed by high performance liquid chromatography. Endocrinology 1991; 129:2466.

    Article  PubMed  CAS  Google Scholar 

  44. Davidson LA, Black M, Carey FA, Logue F, McNicol AM. Lung tumours immunoreactive for parathyroid hormone-related peptide: analysis of serum calcium levels and tumour type. J Pathol 1996; 178:398.

    Article  PubMed  CAS  Google Scholar 

  45. Nishigaki Y, Ohsaki Y, Toyoshima E, Kikuchi K. Increased serum and urinary levels of a parathyroid hormone-related protein COOH terminus in non-small cell lung can cer patients. Clin Cancer Res 1999; 5:1473.

    PubMed  CAS  Google Scholar 

  46. Miki T, Yano S, Hanibuchi M, Sone S. Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice. Oncol Res 2000; 12:209.

    PubMed  CAS  Google Scholar 

  47. Hiraki A, Ueoka H, Bessho A, et al. Parathyroid hor mone-related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia. Cancer 2002; 95:1706.

    Article  PubMed  CAS  Google Scholar 

  48. Blair HC, Athanasou NA. Recent advances in osteoclast biology and pathological bone resorption. Histol Histopathol 2004; 19:189.

    PubMed  CAS  Google Scholar 

  49. Zhang J, Dai J, Qi Y, et al. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clin Invest 2001; 107:1235.

    Article  PubMed  CAS  Google Scholar 

  50. Terpos E, Szydlo R, Apperley JF, et al. Soluble receptor ac tivator of nuclear factor kB ligand (RANKL)/osteoprotegerin (OPG) ratio predicts survival in multiple myeloma. Proposal for a novel prognostic index. Blood 2003; 102:1064.

    Article  PubMed  CAS  Google Scholar 

  51. Standal T, Borset M, Sundan A. Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol 2004a;26:179.

    PubMed  CAS  Google Scholar 

  52. Standal T, Hjorth-Hansen H, Rasmussen T, et al. Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma. Haematologica 2004b;89:174.

    PubMed  CAS  Google Scholar 

  53. O’Regan A. The role of osteopontin in lung disease. Cytokine Growth Factor Rev 2003; 14:479.

    Article  PubMed  CAS  Google Scholar 

  54. Chambers AF, Wilson SM, Kerkvliet N, O’Malley FP, Harris JF, Casson AG. Osteopontin expression in lung cancer. Lung Cancer 1996; 15:311.

    Article  PubMed  CAS  Google Scholar 

  55. Fedarko NS, Jain A, Karadag A, Van Eman MR, Fisher LW. Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res 2001; 7:4060.

    PubMed  CAS  Google Scholar 

  56. Schneider S, Yochim J, Brabender J, et al. Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer. Clin Cancer Res 2004; 10:1588.

    Article  PubMed  CAS  Google Scholar 

  57. Shih LY, Shih HN, Chen TH. Bone resorption activity of osteolytic metastatic lung and breast cancers. J Orthop Res 2004; 22:1161.

    Article  PubMed  CAS  Google Scholar 

  58. Terpos E, Politou M, Rahemtulla A. The role of markers of bone remodeling in multiple myeloma. Blood Rev 2005; 19:125.

    PubMed  Google Scholar 

  59. Izumi M, Nakanishi Y, Takayama K, et al. Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma. Cancer 2001; 91:1487.

    Article  PubMed  CAS  Google Scholar 

  60. Alatas F, Alatas O, Metintas M, Colak O, Erginel S, Harmanci E. Usefulness of bone markers for detection of bone metastases in lung cancer patients. Clin Biochem 2002; 35:293.

    Article  PubMed  CAS  Google Scholar 

  61. Horiguchi T, Tachikawa S, Kondo R, Hirose M, Teruya S, Ishibashi A, Banno K. Usefulness of serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of bone metastasis from lung cancer. Jpn J Clin Oncol 2000; 30:174.

    Article  PubMed  CAS  Google Scholar 

  62. Koizumi M, Takahashi S, Ogata E. Comparison of serum bone resorption markers in the diagnosis of skeletal metastasis. Anticancer Res 2003; 23:4095.

    PubMed  CAS  Google Scholar 

  63. Ebert W, Muley T, Herb KP, Schmidt-Gayk H. Comparison of bone scintigraphy with bone markers in the diagnosis of bone metastasis in lung carcinoma patients. Anticancer Res 2004; 24:3193.

    PubMed  CAS  Google Scholar 

  64. Brown JE, Cook RJ, Major P, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst 2005; 97:59.

    Article  PubMed  CAS  Google Scholar 

  65. Mitsiades C, Sourla A, Doillon C, et al. Three-dimensional type I collagen co-culture systems for the study of cell-cell interactions and treatment response in bone metastases. J Musculoskelet Neuronal Interact 2000; 1:153.

    PubMed  CAS  Google Scholar 

  66. Jung K, Lein M, Stephan C, et al. Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. Int J Cancer 2004; 111:783.

    Article  PubMed  CAS  Google Scholar 

  67. Naumnik W, Chyczewska E, Izycki T, Ossolinska M. Serum levels of osteoprotegerin (OPG) and progastrin releasing peptide (ProGRP) during chemotherapy of lung cancer. Rocz Akad Med Bialymst 2004; 49(suppl 1):88.

    PubMed  Google Scholar 

  68. Kirkbride P, Mackillop WJ, Priestman TJ, Browman G, Gospodarowicz M, Rousseau P. The role of palliative radiotherapy for bone metastases. Can J Oncol 1996; 6(suppl 1):33.

    PubMed  Google Scholar 

  69. Bezjak A. Palliative therapy for lung cancer. Semin Surg Oncol 2003; 21:138.

    Article  PubMed  Google Scholar 

  70. Ishiyama H, Shibata A, Niino K, Hosoya T. Relationship between morphine and radiotherapy for management of symptomatic bone metastases from lung cancer. Support Care Cancer 2004; 12:743.

    Article  PubMed  Google Scholar 

  71. Ratanatharathorn V, Powers WE, Moss WT, Perez CA. Bone metastasis: review and critical analysis of random allocation trials of local field treatment. Int J Radiat Oncol Biol Phys 1999; 44:1.

    Article  PubMed  CAS  Google Scholar 

  72. Wu JS, Bezjak A, Chow E, Kirkbride P. Primary treatment endpoint following palliative radiotherapy for painful bone metastases: need for a consensus definition? Clin Oncol 2002; 14:70.

    Article  Google Scholar 

  73. McQuay HJ, Collins SL, Carroll D, Moore RA. Radiotherapy for the palliation of painful bone metastases. Cochrane Database Syst Rev 2000:CD001793.

    Google Scholar 

  74. Wu JS, Wong R, Johnston M, Bezjak A, Whelan T. Meta analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 2003; 55:594.

    Article  PubMed  Google Scholar 

  75. Chow E, Wu JS, Hoskin P, Coia LR, Bentzen SM, Blitzer PH. International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Radiother Oncol 2002; 64:275.

    Article  PubMed  Google Scholar 

  76. Wedin R. Surgical treatment for pathologic fracture. Acta Orthop Scand Suppl 2001; 72:1.

    Article  Google Scholar 

  77. Kalayci M, Cagavi F, Gul S, Yenidunya S, Acikgoz B. Intramedullary spinal cord metastases: diagnosis and treatment — an illustrated review. Acta Neurochir 2004; 146:1347.

    Article  CAS  Google Scholar 

  78. Fleisch H. Development of bisphosphonates. Breast Cancer Res 2002; 4:30.

    Article  PubMed  CAS  Google Scholar 

  79. Russell RG, Rogers MJ, Frith JC, et al. The pharmacology of bisphosphonates and new insights into their mechanisms of action. J Bone Miner Res 1999; 14(suppl 2):53.

    PubMed  CAS  Google Scholar 

  80. Raje N, Anderson KC. The evolving role of bisphosphonate therapy in multiple myeloma. Blood 2000; 96:381.

    PubMed  CAS  Google Scholar 

  81. Body JJ. Bisphosphonates. Eur J Cancer 1998; 34:263.

    Article  PubMed  CAS  Google Scholar 

  82. Fitton A, McTavish D. Pamidronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs 1991; 41:289.

    PubMed  CAS  Google Scholar 

  83. Plosker GL, Goa KL. Clodronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs 1994; 47:945.

    PubMed  CAS  Google Scholar 

  84. Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev 1998; 19:80.

    Article  PubMed  CAS  Google Scholar 

  85. Lin JH. Bisphosphonates: a review of their pharmacokinetic properties. Bone 1996; 18:75.

    Article  PubMed  CAS  Google Scholar 

  86. Suda T, Nakamura I, Jimi E, Takahashi N. Regulation of osteoclast function. J Bone Miner Res 1997; 12:869.

    Article  PubMed  CAS  Google Scholar 

  87. Fromigue O, Lagneaux L, Body JJ. Bisphosphonates induce breast cancer cell death in vitro. J Bone Miner Res 2000; 15:2211.

    Article  PubMed  CAS  Google Scholar 

  88. Coxon JP, Oades GM, Kirby RS, Colston KW Zoledronic acid induces apoptosis and inhibits adhesion to mineralized matrix in prostate cancer cells via inhibition of protein prenylation. BJU Int 2004; 94:164.

    Article  PubMed  CAS  Google Scholar 

  89. Vorotnjak M, Boos J, Lanvers-Kaminsky C. In vitro toxicity of bisphosphonates on human neuroblastoma cell lines. Anticancer Drugs 2004; 15:795.

    Article  PubMed  CAS  Google Scholar 

  90. Yang DM, Chi CW, Chang HM, et al. Effects of clodronate on cancer growth and Ca2+ signaling of human thyroid carcinoma cell lines. Anticancer Res 2004; 24:1617.

    PubMed  Google Scholar 

  91. Hashimoto K, Morishige K, Sawada K, et al. Alendronate inhibits intraperitoneal dissemination in in vivo ovarian cancer model. Cancer Res 2005; 65:540.

    PubMed  CAS  Google Scholar 

  92. Matsumoto S, Kimura S, Segawa H, et al. Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines. Lung Cancer 2005; 47:31.

    Article  PubMed  Google Scholar 

  93. Zhang H, Yano S, Miki T, et al. A novel bisphosphonate minodronate (YM529) specifically inhibits osteolytic bone metastasis produced by human small-cell lung-cancer cells in NK cell-depleted SCID mice. Clin Exp Metastasis 2003; 20:153.

    Article  PubMed  CAS  Google Scholar 

  94. Yano S, Zhang H, Hanibuchi M, Miki T, Goto H, Uehara H, Sone S. Combined therapy with a new bisphosphonate, minodronate (YM529), and chemotherapy for multiple organ metastases of small cell lung cancer cells in severe combined immunodeficient mice. Clin Cancer Res 2003; 9:5380.

    PubMed  CAS  Google Scholar 

  95. Terpos E, Rahemtulla A. Bisphosphonate treatment for multiple myeloma. Drugs Today 2004; 40:29.

    Article  CAS  PubMed  Google Scholar 

  96. Sato K, Kimura S, Segawa H, et al. Cytotoxic effects of gammadelta T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy. Int J Cancer 2005; 116:94.

    Article  PubMed  CAS  Google Scholar 

  97. Berenson JR, Rosen LS, Howell A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases: a double-blind, randomized dose-response study. Cancer 2001; 91:1191.

    Article  PubMed  CAS  Google Scholar 

  98. Rosen LS, Gordon D, Kaminski M, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001; 7:377.

    PubMed  CAS  Google Scholar 

  99. Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003; 98:1735.

    Article  PubMed  CAS  Google Scholar 

  100. Lipton A, Small E, Saad F, et al. The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both lytic and blastic lesions: a comparison to pamidronate. Cancer Invest 2002; 20(suppl 2):45.

    Article  PubMed  CAS  Google Scholar 

  101. Rosen LS, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial — the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 2003; 21:3150.

    Article  PubMed  CAS  Google Scholar 

  102. Rosen LS, Gordon D, Tchekmedyian NS, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer 2004; 100:2613.

    Article  PubMed  CAS  Google Scholar 

  103. Hirsh V, Tchekmedyian NS, Rosen LS, Zheng M, Hei YJ. Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: analysis based on history of skeletal complications. Clin Lung Cancer 2004; 6:170.

    Article  PubMed  CAS  Google Scholar 

  104. Costa L, Demers LM, Gouveia-Oliveira A, Schaller J, Costa EB, de Moura MC, Lipton A. Prospective evaluation of the peptide-bound collagen type I cross-links N-telopeptide and C-telopeptide in predicting bone metastases status. J Clin Oncol 2002; 20:850.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Haematology Unit, 251 Air Force and VA Hospital, Athens, Greece

    Evangelos Terpos

  2. Oncology Unit Sotiria General Hospital, Athens Medical School, Athens, Greece

    Konstantinos N. Syrigos

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  1. Evangelos Terpos
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Editors and Affiliations

  1. Sotiria General Hospital, Athens Medical School, Athens, Greece

    Konstantinos N. Syrigos MD, PhD

  2. Royal Marsden NHS Trust Hospitals, London, UK

    Christopher M. Nutting MB BA, MD, FRCR

  3. Evangelismos General Hospital, Athens Medical School, Athens, Greece

    Charis Roussos MD, MSc, PhD, MRS, FRCP(C)

  4. Faculty of Medicine, McGill University, Montreal, Canada

    Charis Roussos MD, MSc, PhD, MRS, FRCP(C)

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Terpos, E., Syrigos, K.N. (2006). Pathophysiology and Management of Bone Metastases in Lung Cancer. In: Syrigos, K.N., Nutting, C.M., Roussos, C. (eds) Tumors of the Chest. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-31040-1_48

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