Current knowledge and future directions on bisphosphonate-related osteonecrosis of the jaw in cancer patients

Expert Opinion on Pharmacotherapy

Volumn 9, Issue 8, 2008, Pages 1351-1361

  Adamo, Vincenzo ^a   Caristi, Nicola ^a   Saccà, Marcello Maugeri ^a   Ferraro, Giuseppa ^a   Arcanà, Concetta ^a   Maisano, Roberto ^b   Santini, Daniele ^c   Tonini, Giuseppe ^c  

^a Medical Oncology and Integrated Therapies Unit   (Italy)

^b BIANCHI MELACRINO MORELLI HOSPITAL   (Italy)

^c UNIVERSITY CAMPUS BIO MEDICO   (Italy)

Author keywords

Bisphosphonates; Bone metastases; Osteomyelitis; Osteonecrosis of the jaw

Indexed keywords

3 PEHPC; ALENDRONIC ACID; ANGIOGENESIS INHIBITOR; ANTIBIOTIC AGENT; ANTINEOPLASTIC AGENT; ATRASENTAN; BISPHOSPHONIC ACID DERIVATIVE; BORTEZOMIB; CLODRONIC ACID; CORTICOSTEROID; DENOSUMAB; GLUCOCORTICOID; IBANDRONIC ACID; LIPOSOME; NE 10790; OXYGEN; PAMIDRONIC ACID; PLACEBO; RISEDRONIC ACID; THALIDOMIDE; ZOLEDRONIC ACID; BONE DENSITY CONSERVATION AGENT;

ACUTE LYMPHOBLASTIC LEUKEMIA; ALCOHOL ABUSE; ANALGESIA; ANTIANGIOGENIC ACTIVITY; BONE BLOOD FLOW; BONE DISEASE; BONE INFECTION; BONE METASTASIS; BONE NECROSIS; BONE REMODELING; CANCER HORMONE THERAPY; CANCER PATIENT; CARCINOGENESIS; CLINICAL FEATURE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DEBRIDEMENT; DEMOGRAPHY; DENTAL CARE; DIABETES MELLITUS; DIFFERENTIAL DIAGNOSIS; DISEASE ASSOCIATION; DRUG BIOAVAILABILITY; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG FORMULATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; HIP DISEASE; HUMAN; HYPERBARIC OXYGEN; INCIDENCE; JAW DISEASE; LONG TERM CARE; LOW DRUG DOSE; MALNUTRITION; MASTICATION; MONOTHERAPY; MOUTH DISEASE; MOUTH HYGIENE; MOUTH INFECTION; MOUTHWASH; MULTIPLE MYELOMA; NONHUMAN; PAIN ASSESSMENT; PATIENT EDUCATION; PROSTATE CANCER; QUALITY OF LIFE; RADIATION INJURY; REVIEW; RISK REDUCTION; SMOKING; SOLID TUMOR; TOOTH EXTRACTION; TREATMENT DURATION; VASCULAR DISEASE; BONE; BONE TUMOR; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; PATHOLOGY; RISK FACTOR; VASCULARIZATION;

BONE AND BONES; BONE DENSITY CONSERVATION AGENTS; BONE NEOPLASMS; BONE REMODELING; DIAGNOSIS, DIFFERENTIAL; DIPHOSPHONATES; HUMANS; JAW DISEASES; OSTEONECROSIS; RISK FACTORS;

EID: 45549089828     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.9.8.1351     Document Type: Review

References (118)

1. Fleisch H. Bisphosphonates mechanisms of action. Endocr Rev 1998;19:80-100
2. Russel RG, Croucher PI, Rogers MJ. Bisphosphonates: pharmacology, mechanisms of action and clinical uses. Osteoporos Int 1999;9(Suppl 2):S66-80
3. Rogers MJ. New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des 2003;9:2643-58
4. Schenk R, Eggli P, Fleisch H, Rosini S. Quantitative morphometric evaluation of the inhibitory activity of new amino-bisphosphonates on bone resorption in the rat. Calcif Tissue Int 1986;38:342-9
5. Sietsema WK, Ebetino FH, Salvagno AM, Bevan JA. Antiresorptive dose-response relationship across three generations of bisphosphonates. Drug Exp Clin Res 1989;15:389-96
6. Green JR, Muller K, Jaeggi KA. Preclinical pharmacology of CGP 42'446, a new, potent, heterocyclic bisphosphonate compound. J Bone Miner Res 1994;9:745-51
7. Licata AA. Discovery, clinical development, and therapeutic use of bisphosphonates. Ann Pharmacother 2005;39:668-77
8. Cremers S, Pillai G, Papapoulos SE. Pharmacokinetics/pharmacodynamics of bisphosphonates; use for optimisation of intermittent therapy for osteoporosis. Clin Pharmacokinet 2005;44:551-70
9. Lin JH, Russell G, Gertz B. Pharmacokinetics of alendronate: an overview. Int J Clin Pract Suppl 1999;101:18-26
10. Ensrud KE, Barrett-Connor EL, Schwartz A, at al. Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD, results from the Fracture Intervention Trial long-term extension. J Bone Miner Res 2004;19:1259-69
11. Barret J, Worth E, Bauss F, Epstein S. Ibandronate: a clinical pharmacological and pharmacokinetic update. J Clin Pharmacol 2004;44:951-65
12. Gertz BJ, Holland SD, Kline WF, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 1995;58:288-98
13. Rogers MJ, Russell RG, Blackburn GM, et al. Metabolism of halogenated bisphosphonates by the cellular slime mould Dictyostelium discoideum. Biochem Biophys Res Commun 1992;189:414-23
14. Rogers MJ, Ji X, Russell RG, et al. Incorporation of bisphosphonates into adenine nucleotides by amoebae of the cellular slime mould Dictyostelium discoideum. Biochem J 1994;303:303-11
15. Pelorgeas S, Martin JB, Satre M. Cytotoxicity of dichloromethane diphosphonate and of 1-hydroxyethane-1,1-diphosphonate in the amoebae of the slime mould Dictyostelium discoideum. A 31P NMR study. Biochem Pharmacol 1992;44:2157-63
16. Frith JC, Mönkkönen J, Blackburn GM, et al. Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5′-(beta, gamma-dichloromethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res 1997;12:1358-67
17. Rogers MJ, Brown RJ, Hodkin V, et al. Bisphosphonates are incorporated into adenine nucleotides by human aminoacyl-tRNA synthetase enzymes. Biochem Biophys Res Commun 1996;224:863-9
18. Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer 2000;88(Suppl 12):2961-78
19. Gober HJ, Kistowska M, Angman L, et al. Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells. J Exp Med 2003;197:163-8
20. Luckman SP, Hughes DE, Coxon FP, et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1998;13:581-9
21. Rogers MJ, Frith JC, Luckman SP, et al. Molecular mechanisms of action of bisphosphonates. Bone 1999;24(Suppl 5):73S-79S
22. 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):53-65
23. Green JR. Bisphosphonates: preclinical review. Oncologist 2004;9(Suppl 4):3-13
24. Caraglia M, Santini D, Marra M, et al. Emerging anti-cancer molecular mechanisms of aminobisphosphonates. Endocr Relat Cancer 2006;13:7-26
25. Michaelson MD, Smith MR. Bisphosphonates for treatment and prevention of bone metastases. J Clin Oncol 2005;23:8219-24
26. Hortobagyi GN, Theriault RL, Lipton A, et al. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group. J Clin Oncol 1998;16:2038-44
27. Theriault RL, Upton A, Hortobagyi GN, at al. Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol 1999;17:846-54
28. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 1996;334:488-93
29. Berenson JR, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myleoma Aredia Study Group. J Clin Oncol 1998;16:593-602
30. 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;7:377-87
31. Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety 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;98:1735-44
32. Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458-68
33. Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879-82
34. 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;21:3150-7
35. Body JJ, Kanis J, Diel I, et al. Risk reductions in metastatic breast cancer: multivariate Poisson regression analyses of oral and i.v. ibandronate. Proc Am Soc Clin Oncol 2003;22:46a
36. Body JJ, Diel IJ, Bell R, et al. Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer. Pain 2004;111:306-12
37. Tripathy D, Budde M. Assessing the efficacy of ibandronate for the prevention of skeletal-related events (SREs) in metastatic bone disease: a methodological comparison. Bone 2004;34(Suppl 1):S91
38. Body JJ, Diel IJ, Lichinitser MR, et al. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003;14:1399-405
39. Body JJ, Diel IJ, Lichinitzer M, et al. Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies. Br J Cancer 2004;90:1133-7
40. Kohno N, Aogi K, Minami H, et al. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol 2005;23:3314-21
41. Diel IJ, Body JJ, Lichinitser MR, et al. Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. Eur J Cancer 2004;40:1704-12
42. Smith MR. Zoledronic acid to prevent skeletal complications in cancer: corroborating the evidence. Cancer Treat Rev 2005;31(Suppl 3):19-25
43. Conte P, Guarneri V. Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. Oncologist 2004;9(Suppl 4):28-37
44. Saad F, Sternberg CN. Multidisciplinary management of bone complications in prostate cancer and optimizing outcomes of bisphosphonate therapy. Nat Clin Pract Urol 2007;4(Suppl 1):S3-13
45. Chang JT, Green L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med 2003;349:1676-9
46. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7
47. Migliorati CA. Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol 2003;21:4253-4
48. Ruggiero S, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62:527-34
49. Badros A, Weikel D, Salama A, et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006;24:945-52
50. Bamias A, Kastritis E, Bamia C, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580-7
51. Bagan JV, Jimenez Y, Murillo J, et al. Jaw osteonecrosis associated with bisphosphonates: multiple exposed areas and its relationship to teeth extractions. Study of 20 cases. Oral Oncol 2006;42:327
52. Dimopoulos MA, Kastritis E, Anagnostopoulos A, et al. Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 2006;91:968-71
53. Farrugia MC, Summerlin DJ, Krowiak E, et al. Osteonecrosis of the mandible or maxilla associated with the use of new generation bisphosphonates. Laryngoscope 2006;116:115-20
54. Kanat O, Ozet A, Arpaci F, et al. Bisphosphonate-associated osteonecrosis of the jaws: case reports and analysis of 184 cases [abstract 18595]. 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 2006;24
55. Landesberg R, Wilson T, Grbic JT. Bisphosphonate-associated osteonecrosis of the jaw: conclusions based on an analysis of case series. Dent Today 2006;25:52, 54-7
56. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567-75
57. Melo MD, Obeid G. Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: strategies for prevention and early recognition. J Am Dent Assoc 2005;136:1675-81
58. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol 2006;7:508-14
59. Olson KB, Hellie CM, Pienta KJ. Osteonecrosis of jaw in patient with hormone-refractory prostate cancer treated with zoledronic acid. Urology 2005;66:658
60. Vannucchi AM, Ficarra G, Antonioli, Bosi A. Osteonecrosis of the jaw associated with zoledronate therapy in a patient with multiple mieloma. Br J Haematol 2005;128:738
61. Wallace E, Quintyne K, Cantwell B, et al. Osteonecrosis of the jaw associated with intravenous bisphosphonate therapy - a single institution experience [abstract 18553]. 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 2006;24
62. Zarychanski R, Elphee E, Walton P, Johnston J. Osteonecrosis of the jaw associated with pamidronate therapy. Am J Hematol 2006;81:73-5
63. Zervas K, Verrou E, Teleioudis Z, et al. Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: a single-centre experience in 303 patients. Br J Haematol 2006;134:620-3
64. Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2007;65:369-76
65. Weitzman R, Sauter N, Eriksen EF, et al. Critical review: Updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patient - May 2006. Crit Rev Oncol Hematol 2007;62(2):148-52
66. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22(10):1479-91
67. Peters E, Lovas GL, Wysocki GP. Lingual mandibular sequestration and ulceration. Oral Surg Oral Med Oral Pathol 1993;75(6):739-43
68. Tezal M, Wactawski-Wende J, Grossi SG, et al. Periodontal disease and the incidence of tooth loss in postmenopausal women. J Periodontol 2005;76(7):1123-8
69. Bertoldo F, Santini D, Lo Cascio V. Bisphosphonates and osteomyelitis of the jaw: a pathogenic puzzle. Nat Clin Pract Oncol 2007;4(12):711-21
70. Migliorati CA, Casiglia J, Epstein J, et al. Managing the care of patients with bisphosphonate-associated asteonecrosis. An American Academy of Oral Medicine position paper. J Am Dent Assoc 2005;136(12):1658-68
71. Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer 2005;104(1):83-93
72. Tiranathanagul S, Yongchaitrakul T, Pattamapun K, Pavasant P. Actinobacillus actinomycetemcomitans lipopolysaccharide activates matrix metalloproteinase-2 and increases receptor activator of nuclear factor-kappaB ligand expression in human periodontal ligament cells. J Periodontol 2004;75(12):1647-54
73. Hauge EM, Qvesel D, Eriksen EF, et al. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res 2001;16:1575-82
74. Fournier P, Boissier S, Filleur S, et al. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 2002;62:6538-44
75. Wood J, Bongean K, Ruetz S, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharm Exp Ther 2002;302:1055-61
76. Santini D, Vincenzi B, Avvisati G, et al. Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res 2002;8:1080-4
77. Santini D, Vincenzi B, Dicuonzo G, et al. Zoledronic acid induces significant and lost-lasting modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res 2003;9:2893-7
78. Durie BGM, Katz M, Crowley J. Osteonecrosis of the jaws and bisphosphonates. N Engl J Med 2005;353:99-102
79. Kyle RA, Yee GC, Somerfield MR, et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007;25(17):2464-72
80. Hoff AO, Toth B, Altundag K, et al. Osteonecrosis of the jaw in patients receiving intravenous bisphosphonate therapy. Presented at the 27th Annual Meeting of the American Society for Bone and Mineral Research; 2005 September 22 - 26; Nashville, USA
81. Tosi P, Zamagni E, Cangini D, et al. Osteonecrosis of the jaws in newly diagnosed multiple myeloma patients treated with zoledronic acid and thalidomide-dexamethasone. Blood 2006;108:3951-2
82. Ruggiero S, Gralow J, Marx RE, et al. Practical guidelines for the prevention, diagnosis, and treatment of asteonecrosis of the jaw in patients with cancer. JOP 2006;2:7-14
83. Lam DK, S ndor GKB, Holmes HI, et al. A review of bisphosphonate-associated osteonecrosis of the jaws and its management. J Can Dent Assoc 2007;73(5):417-22
84. Leite AF, Figueiredo PT, Melo NS, et al. Bisphosphonate-associated osteonecrosis of the jaws. Report of a case and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102(1):14-21
85. Dimitrakopoulos I, Magopoulos C, Karakasis D. Bisphosphonate-induced avascular osteonecrosis of the jaws: a clinical report of 11 cases. Int J Oral Maxillofac Surg 2006;35(7):588-93
86. Whyte M, Venhert D, Clements KL, et al. Bisphosphonate-induced osteopetrosis. N Engl J Med 2003;349:457-63
87. Magopoulos C, Karakinaris G, Telioudis Z, et al. Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and treatment proposals. Am J Otolaryngol 2007;28(3):158-63
88. Hellstein JW, Marek CL. Bisphosphonate osteochemonecrosis (bis-phossy jaw): is this phossy jaw of the 21st century? J Oral Maxillofac Surg 2005;63(5):682-9
89. Vormola R, Ortega C, Montemurro F, et al. Osteonecrosis of the jaw (ONJ) in cancer patients with bone metastases treated with zoledronic acid: update an prevention [abstract D124]. Ann Oncol 2007;18(11)
90. Takeyama S, Shinoda H. Pharmacological actions and pharmacokinetics of bisphosphonates. Clin Calcium 2003;13(2):115-21
91. Marx RE. Oral and intravenous bisphosphonate-induced osteonecrosis of the jaws. History, etiology, prevention, and treatment. Quintessence Publishing Co, Inc.; 2007. p. 9-96
92. Allegra A, Oteri G, Nastro E, et al. Patients with bisphosphonates-associated osteonecrosis of the jaw have reduced circulating endothelial cells. Hematol Oncol 2007;18
93. Attal M, Harousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in multiple myeloma patients. Blood 2006;108:3289-94
94. Corso A, Varettoni M, Zappasodi P, et al. A different schedule of zoledronic acid can reduce the risk of the osteonecrosis of the jaw in patients with multiple myeloma. Leukemia 2007;21(7):1545-8
95. Chukwujindu J, Dolin P. Bisphosphonates and jaw osteonecrosis: updated experience with ibandronate. Presented at the 31st European Society for Medical Oncology Congress; 2006 September 29 - October 3; Istanbul, Turkey
96. Rivkin S. Oral ibandronate versus intravenous zoledronic acid for breast cancer patients with skeletal complications: the SWOG trial. Bone 2006;38(Suppl 1):S82
97. Barrett-Lee P, Murray N. Zoledronic acid versus ibandronate comparative evaluation in breast cancer patients with bone metastases: the NCRI ZICE trial. Bone 2006;38(Suppl 1):S57
98. Gazzaniga S, Bravo AI, Guglielmotti A, et al. Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft. J Invest Dermatol 2007;127(8):2031-41
99. Zeisberger SM, Odermatt B, Marty C, et al. Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 2006;95(3):272-81
100. Coxon FP, Helfrich MH, Larijani B, et al. Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages. J Biol Chem 2001;276(51):48213-22
101. Coxon FP, Ebetino FH, Mules EH, et al. Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitro and in vivo. Bone 2005;37(3):349-58
102. Lipton A, Steger GG, Figueroa J, et al. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007;25(28):4431-7
103. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350(16):1655-64
104. Body JJ, Facon T, Coleman RE, et al. 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 2006;12(4):1221-8
105. McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006;354(8):821-31
106. Jimeno A, Carducci M. Atrasentan: targeting the endothelin axis in prostate cancer. Expert Opin Investig Drugs 2004;13:1631
107. Jimeno A, Carducci M. Atrasentan: a novel and rationally designed therapeutic alternative in the management of cancer. Expert Rev Anticancer Ther 2005;5:419
108. Guise TA, Yin JJ, Mohammad KS. Role of endothelin-1 in osteoblastic bone metastases. Cancer 2003;97(S3):779-84
109. Hall CL, Keller ET. The role of Wnts in bone metastases. Cancer Metastasis Rev 2006;25(4):551-8
110. Vogelzang NJ, Nelson JB, Schulman C, et al. Meta-analysis of clinical trials of atrasentan 10 mg in metastatic hormone-refractory prostate cancer. Presented at Multidisciplinary Prostate Cancer Symposium; 2005 February 17 - 19; Orlando, Florida, USA
111. Carducci MA, Saad F, Abrahamsson PA, et al. A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 2007;110(9):1959-66
112. Relling MV, Yang W, Das S, et al. Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. J Clin Oncol 2004;22(19):3930-6
113. Jagdev SP, Coleman RE, Shipman CM, et al. The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer 2001;84:1126-34
114. Neville-Webbe HL, Evans CA, Coleman RE, et al. Zaledronic acid (ZOL) in combination with doxorubicin (DOX) has synergistic effects on apoptosis of breast cancer cells (BCCs) in vitro [abstract]. Presented at the Ivth International Conference on Cancer-Induced Bone Diseases; 2003 December 7 - 9; San Antonio, USA
115. Ullén A, Lennartsson L, Hjelm-Eriksson M, et al. Additive/ synergistic anti-tumoral effect on prostate cancer cells in vitro following treatment with a combination of gemcitabine and zoledronic acid. Proc Am Soc Clin Oncol 2003;22:432
116. Brufsky A, Harker WG, Beck JT, et al. Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol 2007;25(22):829-36
117. Smith MR, Eastham J, Gleason DM, et al. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for non metastatic prostate cancer. J Urol 2003;169:2008-12
118. Daubiné F, Le Gall C, Gasser J, et al. Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis. JNCI 2007;99(4):322-30