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Therapy Insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease

Nature Clinical Practice Oncology volume 4, pages 42–55 (2007)Cite this article

Abstract

Bisphosphonates are a valuable class of drugs with potent anti-resorptive actions that make them ideal for skeletal protection in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget's disease of bone. It has become apparent, however, that these drugs also have the potential to cause a number of adverse effects. While these do not limit bisphosphonate use, the incidence of these adverse events can be minimized if appropriate care is taken with their administration, and by maintaining appropriate surveillance and patient care. We review the range of adverse reactions to bisphosphonate therapy with a particular emphasis on the recently identified association between long-term bisphosphonate treatment and osteonecrosis of the jaw. This is a potentially serious side effect seen mostly in patients with multiple myeloma or breast cancer bone metastases who receive intravenous bisphosphonate treatment. While the etiology is uncertain, a strong association with dental pathology and interventions highlights the need for close attention to dental health in this patient group.

Key Points

  • Bisphosphonates have proven highly beneficial for treatment of diseases characterized by a relative excess in osteoclastic bone resorption

  • Bisphosphonate treatment can reduce fracture risk in osteoporosis, bone pain in Paget's disease of bone, and hypercalcemic and skeletal events in patients with bone metastases

  • Bisphosphonate treatment has, however, been associated with a number of adverse effects including gastrointestinal injury, nephrotoxicity and, more recently, ONJ

  • These adverse effects can be minimized by awareness of risks, care in drug administration, prophylactic dental care, and careful patient monitoring

  • There is an urgent need to understand the etiology of ONJ to improve evaluation of patient risk and to enable the identification of appropriate treatments

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Figure 1: The chemical structures of various bisphosphonates.
Figure 2: Models for bisphosphonate targeting of (A) osteoclasts and (B) macrophages.
Figure 3: Disease distribution in publications detailing bisphosphonate-related ONJ (derived from data in Table 2.)
Figure 4: Presence of a dental history reported in patients in publications detailing bisphosphonate-related ONJ (derived from data in Table 2).

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References

  1. Liberman UA et al. (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333: 1437–1443

    Article  CAS  PubMed  Google Scholar 

  2. Black DM et al. (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348: 1535–1541

    Article  CAS  PubMed  Google Scholar 

  3. Cummings SR et al. (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280: 2077–2082

    Article  CAS  PubMed  Google Scholar 

  4. Pols HA et al. (1999) Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Foxamax International Trial Study Group. Osteoporos Int 9: 461–468

    Article  CAS  PubMed  Google Scholar 

  5. Reginster J et al. (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11: 83–91

    Article  CAS  PubMed  Google Scholar 

  6. Harris ST et al. (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282: 1344–1352

    Article  CAS  PubMed  Google Scholar 

  7. Roux C et al. (2004) Efficacy of risedronate on clinical vertebral fractures within six months. Curr Med Res Opin 20: 433–439

    Article  CAS  PubMed  Google Scholar 

  8. Felsenberg D et al. (2005) Oral ibandronate significantly reduces the risk of vertebral fractures of greater severity after 1, 2, and 3 years in postmenopausal women with osteoporosis. Bone 37: 651–654

    Article  CAS  PubMed  Google Scholar 

  9. Miller PD et al. (2005) Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res 20: 1315–1322

    Article  CAS  PubMed  Google Scholar 

  10. McClung MR et al. (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344: 333–340

    Article  CAS  PubMed  Google Scholar 

  11. Reid IR et al. (2005) Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N Engl J Med 353: 898–908

    Article  CAS  PubMed  Google Scholar 

  12. Ross JR et al. (2003) Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer. BMJ 327: 469–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jagdev SP et al. (2001) Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease. Ann Oncol 12: 1433–1438

    Article  CAS  PubMed  Google Scholar 

  14. Berenson JR et al. (2001) A phase I dose-ranging trial of monthly infusions of zoledronic acid for the treatment of osteolytic bone metastases. Clin Cancer Res 7: 478–485

    CAS  PubMed  Google Scholar 

  15. Glorieux FH et al. (1998) Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 339: 947–952

    Article  CAS  PubMed  Google Scholar 

  16. Astrom E and Soderhall S (2002) Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta. Arch Dis Child 86: 356–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fleisch H et al. (1969) Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165: 1262–1264

    Article  CAS  PubMed  Google Scholar 

  18. Rogers MJ et al. (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88 (Suppl 12): 2961–2978

    Article  CAS  PubMed  Google Scholar 

  19. Lin JH (1996) Bisphosphonates: a review of their pharmacokinetic properties. Bone 18: 75–85

    Article  CAS  PubMed  Google Scholar 

  20. Russell RG et al. (1970) The influence of pyrophosphate, condensed phosphates, phosphonates and other phosphate compounds on the dissolution of hydroxyapatite in vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomised rats. Calcif Tissue Res 6: 183–196

    Article  CAS  PubMed  Google Scholar 

  21. Schenk R et al. (1973) Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl 2 MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcif Tissue Int 11: 326–331

    Google Scholar 

  22. Thompson K et al. (2006) Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis. Mol Pharmacol 69: 1624–1632

    Article  CAS  PubMed  Google Scholar 

  23. Sato M et al. (1991) Bisphosphonate action: alendronate localization in rat bone osteoclast ultrastructure. J Clin Invest 88: 2095–2105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Van Rooijen N et al. (1990) Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome-encapsulated dichloromethylene diphosphonate. Cell Tissue Res 260: 215–222

    Article  CAS  PubMed  Google Scholar 

  25. Rogers MJ (2003) New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des 9: 2643–2658

    Article  CAS  PubMed  Google Scholar 

  26. Evans RA et al. (1983) Pathologic fracture due to severe osteomalacia following diphosphonate treatment of Paget's disease of bone. Aust NZ J Med 13: 277–279

    Article  CAS  Google Scholar 

  27. Boyce BF et al. (1984) Focal osteomalacia due to low-dose diphosphonate therapy in disease. Lancet 1: 821–824

    Article  CAS  PubMed  Google Scholar 

  28. Boyce BF et al. (1994) Mineralisation defects after pamidronate for Paget's. Lancet 343: 1231–1232

    Article  CAS  PubMed  Google Scholar 

  29. Harris S et al. (1982) Secondary hyperparathyroidism associated with dichloromethane diphosphonate treatment of Paget's disease. J Clin Endocrinol Metab 55: 1100–1107

    Article  CAS  PubMed  Google Scholar 

  30. Champallou C et al. (2003) Hypocalcemia following pamidronate administration for bone solid tumor: three clinical case reports. J Pain Symptom Manage 25: 185–190

    Article  PubMed  Google Scholar 

  31. Jones SG et al. (2002) Severe increase in creatinine with hypocalcaemia in myeloma patients receiving zoledronic acid infusions. Br J Haematol 119: 576–577

    Article  CAS  PubMed  Google Scholar 

  32. McIntyre E and Bruera E (1996) Symptomatic hypocalcemia after intravenous pamidronate. J Palliative Care 12: 46–47

    Article  CAS  Google Scholar 

  33. Mishra A et al. (2001) Prolonged, symptomatic hypocalcemia with pamidronate subclinical hypoparathyroidism. Endocrine 14: 159–164

    Article  CAS  PubMed  Google Scholar 

  34. Haworth CS et al. (1998) Severe bone pain after intravenous pamidronate in adult cystic fibrosis. Lancet 352: 1753–1754

    Article  CAS  PubMed  Google Scholar 

  35. Duarte M et al. (1998) The spectrum of bone disease in 200 chronic hemodialysis patients: a correlation between clinical, biochemical and histological findings. Sao Paulo Med J 116: 1790–1797

    Article  CAS  PubMed  Google Scholar 

  36. Mashiba T et al. (2001) Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone 28: 524–531

    Article  CAS  PubMed  Google Scholar 

  37. Bone H et al. (2004) Alendronate Phase III Osteoporosis Treatment Study Group. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350: 1189–1199

    Article  CAS  PubMed  Google Scholar 

  38. Parfitt A (2003) Renal bone disease: a new conceptual framework for the interpretation of bone histomorphometry. Curr Op Nephrol Hypertension 12: 3787–3403

    Google Scholar 

  39. Odvina CV et al. (2001) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90: 1294–1301

    Article  CAS  Google Scholar 

  40. Hewitt RE et al. (2005) The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol 139: 101–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Thompson K and Rogers MJ (2004) Statins prevent bisphosphonate-induced gamma, delta-T-cell proliferation and activation in vitro. J Bone Miner Res 19: 278–288

    Article  CAS  PubMed  Google Scholar 

  42. Adami S et al. (1987) The acute-phase response after bisphosphonate. Calcif Tissue Int 41: 326–331

    Article  CAS  PubMed  Google Scholar 

  43. Reszka AA et al. (2001) Nitrogen-bisphosphonates block retinoblastoma phosphorylation and cell growth by inhibiting the cholesterol biosynthetic pathway in a keratinocyte model for esophageal irritation. Mol Pharmacol 59: 193–202

    Article  CAS  PubMed  Google Scholar 

  44. Lichtenberger L et al. (2000) Effect of bisphosphonates on surface hydrophobicity and phosphatidylcholine concentration of rodent gastric mucosa. Dig Dis Sci 45: 1792–1801

    Article  CAS  PubMed  Google Scholar 

  45. de Groen PC et al. (1996) Esophagitis associated with the use of alendronate. N Engl J Med 335: 1016–1021

    Article  CAS  PubMed  Google Scholar 

  46. Demerjian N et al. (1999) Severe oral ulcerations induced by alendronate. Clin Rheumatol 18: 349–350

    Article  CAS  PubMed  Google Scholar 

  47. Graham DY and Malaty HM (1999) Alendronate gastric ulcers. Aliment Pharmacol Ther 13: 515–519

    Article  CAS  PubMed  Google Scholar 

  48. De S et al. (1995) Pamidronate and uveitis. Br J Rheumatol 34: 479

    Article  CAS  PubMed  Google Scholar 

  49. Durnian JM et al. (2005) Bilateral acute uveitis and conjunctivitis after zoledronic therapy. Eye 19: 221–222

    Article  CAS  PubMed  Google Scholar 

  50. Fraunfelder FW and Fraunfelder FT (2003) Bisphosphonates and ocular inflammation. N Engl J Med 348: 1187–1188

    Article  PubMed  Google Scholar 

  51. Bounameaux HM et al. (1983) Renal failure associated with intravenous diphosphonates. Lancet 1: 471

    Article  CAS  PubMed  Google Scholar 

  52. Chang JT et al. (2003) Renal failure with the use of zoledronic acid. N Engl J Med 349: 1676–1679

    Article  CAS  PubMed  Google Scholar 

  53. Markowitz GS et al. (2001) Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 12: 1164–1172

    CAS  PubMed  Google Scholar 

  54. Munier A et al. (2005) Zoledronic acid and renal toxicity: data from French adverse effect reporting database. Ann Pharmacother 39: 1194–1197

    Article  CAS  PubMed  Google Scholar 

  55. Rosen LS et al. (2001) 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 7: 377–387

    CAS  PubMed  Google Scholar 

  56. Markowitz GS et al. (2003) Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 64: 281–289

    Article  CAS  PubMed  Google Scholar 

  57. Marx R et al. (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaw: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63: 1567–1575

    Article  PubMed  Google Scholar 

  58. Wang J et al. (2003) Osteonecrosis of the jaws associated with cancer chemotherapy. J Oral Maxillofac Surg 61: 1104–1107

    Article  CAS  PubMed  Google Scholar 

  59. Ruggiero SL et al. (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62: 527–534

    Article  PubMed  Google Scholar 

  60. Tarassoff P and Csermak K (2003) Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillofac Surg 61: 1238–1239

    Article  PubMed  Google Scholar 

  61. Carter G et al. (2001) Bisphosphonates and avascular necrosis of the jaw. Med J Aust 182: 413–415

    Google Scholar 

  62. Bamias A et al. (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 23: 8580–8587

    Article  PubMed  Google Scholar 

  63. Durie BG et al. (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353: 99–102

    Article  CAS  PubMed  Google Scholar 

  64. Lenz JH et al. (2005) Does avascular necrosis of the jaws in cancer patients only occur following treatment with bisphosphonates? Craniomaxillofac Surg 33: 395–403

    Article  Google Scholar 

  65. Sung EC et al. (2002) Osteonecrosis of the maxilla as a complication to chemotherapy: a case report. Spec Care Dentist 22: 142–146

    Article  PubMed  Google Scholar 

  66. Schwartz HC (1982) Osteonecrosis of the jaws: a complication of cancer chemotherapy. Head Neck Surg 4: 251–253

    Article  CAS  PubMed  Google Scholar 

  67. Manolagas S and Weinstein R (1999) New developments in the pathogenesis and treatment of steroid-induced osteoporosis J Bone Miner Res 14: 1061–1066

    Article  CAS  PubMed  Google Scholar 

  68. Frost HM (1960) In vivo osteocyte death. J Bone Joint Surg 42A: 138–143

    Article  Google Scholar 

  69. Cowan J et al. (1995) Glucocorticoid therapy for myasthenia gravis resulting in resorption of the mandibular condyles. J Oral Maxillofac Surg 53: 1091–1096

    Article  CAS  PubMed  Google Scholar 

  70. Anderson G et al. (2006) Thalidomide derivative CC-4047 inhibits osteoclast formation by down regulation of PU.1. Blood 107: 3098–3105

    Article  CAS  PubMed  Google Scholar 

  71. Crane E and List A (2005) Immunomodulatory drugs. Cancer Invest 23: 625–634

    Article  CAS  PubMed  Google Scholar 

  72. Ficarra G et al. (2005) Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment. J Clin Periodontol 32: 1123–1128

    Article  CAS  PubMed  Google Scholar 

  73. Epstein J et al. (1997) Postradiation osteonecrosis of the mandible: a long-term follow-up study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 83: 657–662

    Article  CAS  PubMed  Google Scholar 

  74. Migliorati CA (2003) Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol 21: 4253–4254

    Article  PubMed  Google Scholar 

  75. Wooltorton E (2005) Patients receiving intravenous bisphosphonates should avoid invasive dental procedures. CMAJ 172: 1684

    Article  PubMed  PubMed Central  Google Scholar 

  76. Melo MD and Obeid G (2005) Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: strategies for prevention and early recognition. J Am Dent Assoc 136: 1675–1681

    Article  CAS  PubMed  Google Scholar 

  77. Plotkin LI et al. (2005) Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 280: 7317–7325

    Article  CAS  PubMed  Google Scholar 

  78. Bekker PJ et al. (2004) A single dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to nuclear factor-B ligand (RANKL), in postmenopausal women. J Bone Miner Res 19: 1059–1066

    Article  CAS  PubMed  Google Scholar 

  79. Murphy MG et al. (2005) Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 90: 2022–2028

    Article  CAS  PubMed  Google Scholar 

  80. Wood J et al. (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302: 1055–1061

    Article  CAS  PubMed  Google Scholar 

  81. Santini D et al. (2002) Pamidronate induces modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res 8: 1080–1084

    CAS  PubMed  Google Scholar 

  82. Vincenzi B et al. (2003) Bisphosphonates: new antiangiogenic molecules in cancer treatment? Ann Oncol 14: 806–807

    Article  CAS  PubMed  Google Scholar 

  83. Bartl R et al. (2006) Bisphosphonate. [German] In Bisphosphonat-Manual, 83–88 (Eds Bartl R et al.) New York: Springer Berlin-Heidelberg

    Chapter  Google Scholar 

  84. Abu-Id MH et al. (2006) Bisphosphonate-associated osteonecrosis of the jaw [German]. Mund Kiefer Gesichtschir 10: 73–81

    Article  CAS  PubMed  Google Scholar 

  85. Badros A et al. (2006) Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 24: 945–952

    Article  CAS  PubMed  Google Scholar 

  86. Bagan JV et al. (2005) Avascular jaw osteonecrosis in association cancer chemotherapy: series of 10 cases. Med Oral Patol Oral Cir Bucal 10 (Suppl 2): E88–E91

    PubMed  Google Scholar 

  87. Bagan JV et al. (2005) Jaw osteonecrosis associated with bisphosphonates: multiple exposed areas and its relationship to teeth extractions—study of 20 cases. Oral Oncol 42: 327–329

    Article  PubMed  Google Scholar 

  88. Farrugia MC et al. (2006) Osteonecrosis of the mandible or maxilla associated with the use of new generation bisphosphonates. Laryngoscope 116: 115–120

    Article  PubMed  Google Scholar 

  89. Gibbs SD et al. (2005) Bisphosphonate-induced osteonecrosis of the jaw requires early detection and intervention. Med J Aust 183: 549–550

    PubMed  Google Scholar 

  90. Guarneri V et al. (2005) Renal safety and efficacy of i.v. bisphosphonates in patients with skeletal metastases treated for up to 10 years. Oncologist 10: 842–848

    Article  CAS  PubMed  Google Scholar 

  91. Hoefert S and Eufinger H (2005) Kieferknochennekrosen als mögliche unerwünschte Wirkung von Bisphosphonaten [German]. Mund Kiefer Gesichts Chir 9: 233–238

    Article  CAS  Google Scholar 

  92. Hoff A et al. (2005) Osteonecrosis of the jaw in patients receiving intravenous bisphosphonate therapy [abstract #1218]. J Bone Miner Res 20 (Suppl 1): S55

    Google Scholar 

  93. Junod AF et al. (2005) Osteonecrosis of the jaws and bisphosphonates [French]. Rev Med Suisse 1: 2537–2540

    CAS  PubMed  Google Scholar 

  94. Lugassy G et al. (2004) Severe osteomyelitis of the jaw in long-term survivors of multiple myeloma: a new clinical entity. Am J Med 117: 440–441

    Article  PubMed  Google Scholar 

  95. Maerevoet M et al. (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353: 99–102

    Article  PubMed  Google Scholar 

  96. Markiewicz MR et al. (2005) Bisphosphonate-associated osteonecrosis of the jaws: a review of current knowledge. J Am Dent Assoc 136: 1669–1674

    Article  PubMed  Google Scholar 

  97. Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61: 1115–1118

    Article  PubMed  Google Scholar 

  98. Merigo E et al. (2005) Jawbone necrosis without previous dental extractions associated with the use of bisphosphonates (pamidronate and zoledronate): a four-case report. J Oral Pathol Med 34: 613–617

    Article  CAS  PubMed  Google Scholar 

  99. Najm SA et al. (2005) Bisphosphonates-related jaw osteonecrosis [French]. Presse Med 34: 1073–1077

    Article  Google Scholar 

  100. Pastor-Zuazaga D et al. (2006) Osteonecrosis of the jaws and bisphosphonates: report of three cases. Med Oral Patol Oral Cir Bucal 11: E76–E79

    PubMed  Google Scholar 

  101. Purcell PM and Boyd IW (2005) Bisphosphonates and osteonecrosis of the jaw. Med J Aust 182: 417–418

    PubMed  Google Scholar 

  102. Sanna G et al. (2005) Jaw avascular bone necrosis associated with long-term use of bisphosphonates. Ann Oncol 16: 1207–1208

    Article  CAS  PubMed  Google Scholar 

  103. Schirmer I et al. (2005) Bisphosphonates and osteonecrosis of the jaw [German]. Mund Kiefer Gesichtschir 9: 239–245

    Article  CAS  PubMed  Google Scholar 

  104. Schwartz HC (2004) Osteonecrosis and bisphosphonates: correlation versus causation. J Oral Maxillofac Surg 62: 763–764

    Article  PubMed  Google Scholar 

  105. Zarychanski R et al. (2006) Osteonecrosis of the jaw associated with pamidronate therapy. Am J Hematol 81: 73–75

    Article  PubMed  Google Scholar 

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Acknowledgements

Dr Julie M Brown assisted in manuscript preparation. Dr Colin R Dunstan receives funding from the Government of New South Wales (BioFirst Award) and the National Health and Medical Research Council of Australia.

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Authors and Affiliations

  1. CR Dunstan is the Principal Research Fellow and MJ Seibel is Professor and Chair of Endocrinology, at the Bone Research Program, ANZAC Research Institute, University of Sydney, Australia.,

    Colin R Dunstan & Markus J Seibel

  2. D Felsenberg is President of the German Society of Muscle and Bone Research, and is Director of the Centre of Muscle and Bone Research at the Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.,

    Dieter Felsenberg

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Dunstan, C., Felsenberg, D. & Seibel, M. Therapy Insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease. Nat Rev Clin Oncol 4, 42–55 (2007). https://doi.org/10.1038/ncponc0688

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