Journal of Bone and Mineral Metabolism

, Volume 28, Issue 4, pp 365–383 | Cite as

Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons

  • Toshiyuki Yoneda
  • Hiroshi Hagino
  • Toshitsugu Sugimoto
  • Hiroaki Ohta
  • Shunji Takahashi
  • Satoshi Soen
  • Akira Taguchi
  • Satoru Toyosawa
  • Toshihiko Nagata
  • Masahiro Urade


Bisphosphonates (BPs) have been widely, efficiently, and safely used for the treatment of osteoporosis, malignant hypercalcemia, bone metastasis of solid cancers, and multiple myeloma bone diseases. Accumulating recent reports describe that surgical dental treatments in patients with cancer or osteoporosis who have been receiving intravenous or oral BPs are associated with osteonecrosis of the jaw (bisphosphonate-related osteonecrosis of the jaw, BRONJ). The accurate incidence, clinical backgrounds, and pathogenesis of BRONJ have been unclear and appropriate approaches for prevention and treatment have not been established to date. To address the current situation of BRONJ in Japan, the “Allied Task Force Committee of Bisphosphonate-Related Osteonecrosis of the Jaw,” consisting of physicians specializing in bone biology, orthopedic surgery, rheumatology, obstetrics/gynecology, and medical oncology and dentists specializing in oral surgery, periodontology, dental radiology, and oral pathology, was organized. The committee attempted to propose a standard position paper for the treatment of BRONJ. The committee expects that this proposal will provide objective and correct scientific information on BRONJ and will serve as a reference for conducting dental procedures for patients receiving BPs and in designing prevention and treatment of BRONJ. However, because this position paper is not based on direct clinical evidence, it should be used as a reference, and a decision on treatment in each case should be made after an extensive discussion among physicians, dentists/oral surgeons, and the patients.


Bone resorption Osteoclasts Oral bacteria Osteomyelitis Team care system 


  1. 1.
    Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH (2007) Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 1117:209–257CrossRefPubMedGoogle Scholar
  2. 2.
    McCauley LK, Li X (2007) Distinguishing features of the oral cavity and its predisposition to osteonecrosis. J Musculoskelet Neuronal Interact 7:356–357PubMedGoogle Scholar
  3. 3.
    Marx RE, Cillo JE Jr, Ulloa JJ (2007) Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 65:2397–2410CrossRefPubMedGoogle Scholar
  4. 4.
    Huja SS, Beck FM (2008) Bone remodeling in maxilla, mandible, and femur of young dogs. Anat Rec 291:1–5CrossRefGoogle Scholar
  5. 5.
    Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws (2007) 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 65:369–376Google Scholar
  6. 6.
    Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B, American Association of Oral, Maxillofacial Surgeons (2009) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws–2009 update. J Oral Maxillofac Surg 67(5 Suppl):2–12PubMedGoogle Scholar
  7. 7.
    Otto S, Hafner S, Grötz KA (2009) The role of inferior alveolar nerve involvement in bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg 67:589–592CrossRefPubMedGoogle Scholar
  8. 8.
    Assael LA (2009) Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies. J Oral Maxillofac Surg 67(5 Suppl):35–43CrossRefPubMedGoogle Scholar
  9. 9.
    Nusair YM, Younis MH (2007) Prevalence, clinical picture, and risk factors of dry socket in a Jordanian dental teaching center. J Contemp Dent Pract 8:53–63PubMedGoogle Scholar
  10. 10.
    Woo SB, Hellstein JW, Kalmar JR (2006) Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMedGoogle Scholar
  11. 11.
    Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K, Cui J, Adamus A, Gagel RF, Hortobagyi GN (2008) Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23:826–836CrossRefPubMedGoogle Scholar
  12. 12.
    Wilkinson GS, Kuo YF, Freeman JL, Goodwin JS (2007) Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis. J Natl Cancer Inst 99:1016–1024CrossRefPubMedGoogle Scholar
  13. 13.
    Boonyapakorn T, Schirmer I, Reichart PA, Sturm I, Massenkeil G (2008) Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol 44:857–869CrossRefPubMedGoogle Scholar
  14. 14.
    Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 23:8580–8587CrossRefPubMedGoogle Scholar
  15. 15.
    Estefania Fresco R, Ponte Fernandez R, Aguirre Urizar JM (2006) Bisphosphonates and oral pathology II. Osteonecrosis of the jaws: review of the literature before 2005. Med Oral Patol Oral Cir Bucal 11:E456–E461PubMedGoogle Scholar
  16. 16.
    Durie BG, Katz M, Crowley J (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–102CrossRefPubMedGoogle Scholar
  17. 17.
    Maerevoet M, Martin C, Duck L (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–102CrossRefPubMedGoogle Scholar
  18. 18.
    Mavrokokki T, Cheng A, Stein B, Goss A (2007) Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415–423CrossRefPubMedGoogle Scholar
  19. 19.
    Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S et al (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679–691CrossRefPubMedGoogle Scholar
  20. 20.
    Brufsky AM, Bosserman LD, Caradonna RR, Haley BB, Jones CM, Moore HC, Jin L, Warsi GM, Ericson SG, Perez EA (2009) Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results. Clin Breast Cancer 9:77–85CrossRefPubMedGoogle Scholar
  21. 21.
    Grbic JT, Landesberg R, Lin SO, Mesenbrink P, Teid IR, Leung PC, Casas N, Recknor CP, Hua Y, Delmas PD, Eriksen EF (2008) Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yeary pivotal fracture trial. J Am Dent Assoc 139:32–40PubMedGoogle Scholar
  22. 22.
    Felsenberg D, Hoffmeister B, Amling M, Seibel MJ, Fratzl P (2006) Kiefernekrosen nach hoch dosierter bisphosphonattherapie. Dtsch Arzebl 103:3078–3081Google Scholar
  23. 23.
    Edwards BJ, Hellstein JW, Jacobsen PL, Kaltman S, Mariotti A, Migliorati CA (2008) American Dental Association Council on Scientific Affairs Expert Panel on Bisphosphonate-Associated Osteonecrosis of the Jaw. Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 139:1674–1677PubMedGoogle Scholar
  24. 24.
    Phal PM, Myall RW, Assael LA, Weissman JL (2007) Imaging findings of bisphosphonate-associated osteonecrosis of the jaws. AJNR Am J Neuroradiol 28:1139–1145CrossRefPubMedGoogle Scholar
  25. 25.
    Marx RE (2006) Oral and intravenous bisphosphonate-induced osteonecrosis of the jaws: history, etiology, prevention, and treatment. Quintessence Publishing, Carol Stream, ILGoogle Scholar
  26. 26.
    Chiandussi S, Biasotto M, Dore F, Cavalli F, Cova MA, Di Lenarda R (2006) Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofac Radiol 35:236–243CrossRefPubMedGoogle Scholar
  27. 27.
    Bianchi SD, Scoletta M, Cassione FB, Migliaretti G, Mozzati M (2007) Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:249–258CrossRefPubMedGoogle Scholar
  28. 28.
    Raje N, Woo SB, Hande K, Yap JT, Richardson PG et al (2008) Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw. Clin Cancer Res 14:2387–2395CrossRefPubMedGoogle Scholar
  29. 29.
    Treister N, Sheehy N, Bae EH, Friedland B, Lerman M, Woo S (2009) Dental panoramic radiographic evaluation in bisphosphonate-associated osteonecrosis of the jaws. Oral Dis 15:88–92CrossRefPubMedGoogle Scholar
  30. 30.
    Bedogni A, Blandamura S, Lokmic Z, Palumbo C, Ragazzo M, Ferrari F, Tregnaghi A, Pietrogrande F, Procopio O, Saia G, Ferretti M, Bedogni G, Chiarini L, Ferronato G, Ninfo V, Lo Russo L, Lo Muzio L, Nocini PF (2008) Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:358–364CrossRefPubMedGoogle Scholar
  31. 31.
    Bisdas S, Chambron Pinho N, Smolarz A, Sader R, Vogl TJ, Mack MG (2008) Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings in 32 patients. Clin Radiol 63:71–77CrossRefPubMedGoogle Scholar
  32. 32.
    Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR et al (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res 22:1479–1491CrossRefPubMedGoogle Scholar
  33. 33.
    Mawardi H, Treister N, Richardson P, Anderson K, Munshi N, Faiella RA, Woo SB (2009) Sinus tracts—an early sign of bisphosphonate-associated osteonecrosis of the jaws? J Oral Maxillofac Surg 67:593–601CrossRefPubMedGoogle Scholar
  34. 34.
    Garcia-Ferrer L, Bagin JV, Martinez-Sanjuan V, Hernandez-Bazan S, Garcia R, Jiminez-Soriano Y, Hervas V (2008) MRI of mandibular osteonecrosis secondary to bisphosphonates. AJR Am J Roentgenol 190:949–955CrossRefPubMedGoogle Scholar
  35. 35.
    Zanglis A, Andreopoulos D, Dima M, Baltas G, Baziotis N (2007) Jaw uptake of technetium-99 methylene diphosphonate in patients on biphosphonates: a word of caution. Hell J Nucl Med 10:177–180PubMedGoogle Scholar
  36. 36.
    O’Ryan FS, Khoury S, Liao W, Han MM, Hui RL, Baer D, Martin D, Liberty D, Lo JC (2009) Intravenous bisphosphonate-related osteonecrosis of the jaw: bone scintigraphy as an early indicator. J Oral Maxillofac Surg 67:1363–1372CrossRefPubMedGoogle Scholar
  37. 37.
    Ho L, Quan V, Henderson R (2008) Zoledronate-related osteonecrosis of the mandible. Clin Nucl Med 33:68–70CrossRefPubMedGoogle Scholar
  38. 38.
    Krishnan A, Arslanoglu A, Yildirm N, Silbergleit R, Aygun N (2009) Imaging findings of bisphosphonate-related osteonecrosis of the jaw with emphasis on early magnetic resonance imaging findings. J Comput Assist Tomogr 33:298–304CrossRefPubMedGoogle Scholar
  39. 39.
    Hansen T, Kunkel M, Weber A, James Kirkpatrick C (2006) Osteonecrosis of the jaws in patients treated with bisphosphonates: histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 35:155–160CrossRefPubMedGoogle Scholar
  40. 40.
    Dodson TB, Raje NS, Caruso PA, Rosenberg AE (2008) Case records of the Massachusetts General Hospital Case 9–2008. A 65-year-old woman with a nonhealing ulcer of the jaw. N Engl J Med 358:1283–1291CrossRefPubMedGoogle Scholar
  41. 41.
    Kim HK (2007) Introduction to osteonecrosis of the femoral head (OFH) and osteonecrosis of the jaw (ONJ). J Musculoskelet Neuronal Interact 7:350–353PubMedGoogle Scholar
  42. 42.
    Bertoldo F, Santini D, Lo Cascio V (2007) Bisphosphonates, osteomyelitis of the jaw: a pathogenic puzzle. Nat Clin Pract Oncol 4:711–721CrossRefPubMedGoogle Scholar
  43. 43.
    Hansen T, Kunkel M, Springer E, Walter C, Weber A, Siegel E, Kirkpatrick CJ (2007) Actinomycosis of the jaws—histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Arch 451:1009–1017CrossRefPubMedGoogle Scholar
  44. 44.
    Hansen T, Kirkpatrick CJ, Walter C, Kunkel M (2006) Increased numbers of osteoclasts expressing cysteine proteinase cathepsin K in patients with infected osteoradionecrosis and bisphosphonate-associated osteonecrosis: a paradoxical observation? Virchows Arch 449:448–454Google Scholar
  45. 45.
    Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G, Liberman UA, Delmas PD, Malice MP, Czachur M, Daifotis AG (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 339:292–299CrossRefPubMedGoogle Scholar
  46. 46.
    Favio G, Piilloli GP, Maiorano E (2009) Histologic and histomorphometric features of bisphosphonate-related osteonecrosis of the jaws: an analysis of 31 cases with confocal laser scanning microscopy. Bone (NY) 45:406–413Google Scholar
  47. 47.
    Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, Clezardin P (2002) Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 62:6538–6544PubMedGoogle Scholar
  48. 48.
    Santini D, Vincenzi B, Avvisati G, Dicuonzo G, Battistoni F, Gavasci M, Salerno A, Denaro V, Tonini G (2002) Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res 8:1080–1084PubMedGoogle Scholar
  49. 49.
    Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117CrossRefPubMedGoogle Scholar
  50. 50.
    Hoefert S, Schmitz I, Tannapfel A, Eufinger H (2009) Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of symptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings. Clin Oral Invest (in press)Google Scholar
  51. 51.
    Hazenberg JG, Freeley M, Foran E, Lee TC, Taylor D (2006) Microdamage: a cell-transducing mechanism based on ruptured osteocyte processes. J Biomech 39:2096–2103CrossRefPubMedGoogle Scholar
  52. 52.
    Baim S, Miller PD (2009) Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res 24:561–574CrossRefPubMedGoogle Scholar
  53. 53.
    Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR et al (2008) Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 66:1320–1321CrossRefPubMedGoogle Scholar
  54. 54.
    Lehrer S, Montazem A, Ramanathan L, Pessin-Minsley M, Pfail J, Stock RG, Kogan R (2008) Normal serum bone markers in bisphosphonate-induced osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 67:159–161Google Scholar
  55. 55.
    Fantasia JE (2009) Bisphosphonates—what the dentist needs to know: practical considerations. J Oral Maxillofac Surg 67(5 Suppl):53–60CrossRefPubMedGoogle Scholar
  56. 56.
    Badros A, Weikel D, Salama A, Goloubeva O, Schneider A, Rapoport A, Fenton R, Gahres N, Sausville E, Ord R, Meiller T (2006) Osteonecrosis of the jaw in multiple myeloma patients. Clinical features and risk factors. J Clin Oncol 24:945–952CrossRefPubMedGoogle Scholar
  57. 57.
    Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534CrossRefPubMedGoogle Scholar
  58. 58.
    Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63:1567–1575CrossRefPubMedGoogle Scholar
  59. 59.
    Jeffcoat MK (2006) Safety of oral bisphosphonates: controlled studies on alveolar bone. Int J Oral Maxillofac Implants 21:349–353PubMedGoogle Scholar
  60. 60.
    Bell BM, Bell RE (2008) Oral bisphosphonates and dental implants: a retrospective study. J Oral Maxillofac Surg 66:1022–1024CrossRefPubMedGoogle Scholar
  61. 61.
    Grant BT, Amenedo C, Freeman K, Kraut RA (2008) Outcomes of placing dental implants in patients taking oral bisphosphonates: a review of 115 cases. J Oral Maxillofac Surg 66:223–230CrossRefPubMedGoogle Scholar
  62. 62.
    Khamaisi M, Regev E, Yarom N, Avni B, Leitersdorf E, Raz I, Elad S (2007) Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab 92:1172–1175CrossRefPubMedGoogle Scholar
  63. 63.
    Wessel JH, Dodson TB, Zavras AI (2008) Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case-control study. J Oral Maxillofac Surg 66:625–631CrossRefPubMedGoogle Scholar
  64. 64.
    Lehrer S, Montazem A, Ramanathan L, Pessin-Minsley M, Pfail J, Stock RG, Kogan R (2009) Bisphosphonate-induced osteonecrosis of the jaws, bone markers, and a hypothesized candidate gene. J Oral Maxillofac Surg 67:159–161CrossRefPubMedGoogle Scholar
  65. 65.
    Sarasquete ME, Garcia-Sanz R, Marin L, Alcoceba M, Chillon MC, Balanzategui A, Santamaria C, Rosinol L, de la Rubia J, Hernandez MT, Garcia-Navarro I, Lahuerta JJ, Gonzalez M, San Miguel JF (2008) Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood 112:2709–2712CrossRefPubMedGoogle Scholar
  66. 66.
    Ficarra G, Beninati F, Rubino I, Vannucchi A, Longo G, Tonelli P, Pini Prato G (2005) Osteonecrosis of the jaw in periodontal patients with a history of bisphosphonates treatment. J Clin Periodontol 32:1123–1128CrossRefPubMedGoogle Scholar
  67. 67.
    Sarathy AP, Bourgeois SL Jr, Goodell GG (2005) Bisphosphonate-associated osteonecrosis of the jaws and endodontic treatment: two case reports. J Endod 31:759–763CrossRefPubMedGoogle Scholar
  68. 68.
    Migliorati CA, Siegel MA, Elting LS (2006) Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol 7:508–514CrossRefPubMedGoogle Scholar
  69. 69.
    Palomo L, Bissada N, Liu J (2006) Bisphosphonate therapy for bone loss in patients with osteoporosis and periodontal disease: clinical perspectives and review of the literature. Quintessence Int 37:103–107PubMedGoogle Scholar
  70. 70.
    Dodson TB (2009) Intravenous bisphosphonate therapy and bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67(5 Suppl):44–52CrossRefPubMedGoogle Scholar
  71. 71.
    Soileau KM (2006) Oral post-surgical complications following the administration of bisphosphonates given for osteopenia related to malignancy. J Periodontol 77:738–743CrossRefPubMedGoogle Scholar
  72. 72.
    Khan AA, Sandor GK, Dore E, Morrison AD, Alsahli M et al (2008) Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheumatol 35:1391–1397PubMedGoogle Scholar
  73. 73.
    Rizzoli R, Burlet N, Cahall D, Delmas PD, Eriksen EF, Felsenberg D, Grbic J, Jontell M, Landesberg R, Laslop A, Wollenhaupt M, Papapoulos S, Sezer O, Sprafka M, Reginster JY (2008) Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis. Bone (NY) 42:841–847Google Scholar
  74. 74.
    Dannemann C, Grtz KW, Riener MO, Zwahlen RA (2007) Jaw osteonecrosis related to bisphosphonate therapy: a severe secondary disorder. Bone (NY) 40:828–834Google Scholar
  75. 75.
    Allen MR, Burr DB (2009) The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67(5 Suppl):61–70CrossRefPubMedGoogle Scholar
  76. 76.
    Sedghizadeh PP, Kumar SK, Gorur A, Schaudinn C, Shuler CF, Costerton JW (2008) Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy. J Oral Maxillofac Surg 66:767–775CrossRefPubMedGoogle Scholar
  77. 77.
    Kobayashi Y, Hiraga T, Ueda A, Wang L, Matsumoto-Nakano M, Hata K, Yatani H, Yoneda T (2010) Zoledronic acid delays wound healing of the tooth extraction socket, inhibits oral epithelial cell migration and promotes proliferation and adhesion to hydroxyapatite of oral bacteria, with causing no osteonecrosis of the jaw in mice. J Bone Miner Metab (in press)Google Scholar
  78. 78.
    Wood J, Bonjean K, Ruetz S, Bellahcène A, Devy L, Foidart JM, Castronovo V, Green JR (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061CrossRefPubMedGoogle Scholar
  79. 79.
    Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G 3rd, Huryn JM (2008) Osteonecrosis of the jaw related to bevacizumab. J Clin Oncol 26:4037–4038CrossRefPubMedGoogle Scholar
  80. 80.
    Reid IR, Bolland MJ, Grey AB (2007) Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone (NY) 41:318–320Google Scholar
  81. 81.
    Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S, Sinha S, Garrett-Sinha L, Raghavan S (2008) Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg 66:839–847CrossRefPubMedGoogle Scholar
  82. 82.
    Reid IR (2009) Osteonecrosis of the jaw: who gets it, and why? Bone (NY) 44:4–10Google Scholar
  83. 83.
    Allen MR, Burr DB (2008) Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment. J Oral Maxillofac Surg 66:987–994CrossRefPubMedGoogle Scholar
  84. 84.
    Sonis ST, Watkins BA, Lyng GD, Lerman MA, Anderson KC (2009) Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients. Oral Oncol 45:164–172CrossRefPubMedGoogle Scholar
  85. 85.
    Ripamonti CI, Maniezzo M, Campa T, Fagnoni E, Brunelli C, Saibene G, Bareggi C, Ascani L, Cislaghi E (2009) Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 20:137–145CrossRefPubMedGoogle Scholar
  86. 86.
    Dimopoulos MA, Kastritis E, Bamia C, Melakopoulos I, Gika D, Roussou M, Migkou M, Eleftherakis-Papaiakovou E, Christoulas D, Terpos E, Bamias A (2009) Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 20:117–120CrossRefPubMedGoogle Scholar
  87. 87.
    Fleisch H, Reszka A, Rodan G, Rogers M (2002) Bisphosphonates: mechanisms of action. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology, 2nd edn. Academic Press, San Diego, pp 1361–1385Google Scholar
  88. 88.
    Terpos E, Sezer O, Croucher PI, García-Sanz R, Boccadoro M, San Miguel J, Ashcroft J, Bladé J, Cavo M, Delforge M, Dimopoulos MA, Facon T, Macro M, Waage A, Sonneveld P (2009) The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network. Ann Oncol 20:1303–1317CrossRefPubMedGoogle Scholar
  89. 89.
    Rauch F, Glorieux FH (2004) Osteogenesis imperfecta. Lancet 363:1377–1385CrossRefPubMedGoogle Scholar
  90. 90.
    Brown JE, Thomson CS, Ellis SP, Gutcher SA, Purohit OP, Coleman RE (2003) Bone resorption predicts for skeletal complications in metastatic bone disease. Br J Cancer 89:2031–2037CrossRefPubMedGoogle Scholar
  91. 91.
    Chahine C, Cheung MS, Head TW, Schwartz S, Glorieux FH, Rauch F (2008) Tooth extraction socket healing in pediatric patients treated with intravenous pamidronate. J Pediatr 153:719–720CrossRefPubMedGoogle Scholar
  92. 92.
    Malmgren B, Astrom E, Soderhall S (2008) No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonates. J Oral Pathol Med 37:196–200PubMedCrossRefGoogle Scholar
  93. 93.
    Curtis JR, Westfall AO, Cheng H, Delzell E, Saag KG (2008) Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int 19:1613–1620CrossRefPubMedGoogle Scholar
  94. 94.
    Melo MD, 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 136:1675–1681PubMedGoogle Scholar
  95. 95.
    Migliorati CA, Schubert MM, Peterson DE, Seneda LM (2005) Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer (Phila) 104:83–93CrossRefGoogle Scholar
  96. 96.
    Carlson ER, Basile JD (2009) The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67(5 Suppl):85–95CrossRefPubMedGoogle Scholar
  97. 97.
    Marx RE (2009) Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws. J Oral Maxillofac Surg 67(5 Suppl):107–119CrossRefPubMedGoogle Scholar
  98. 98.
    Freiberger JJ (2009) Utility of hyperbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67(5 Suppl):96–106CrossRefPubMedGoogle Scholar
  99. 99.
    Harper RP, Fung E (2007) Resolution of bisphosphonate-associated osteonecrosis of the mandible: possible application for intermittent low-dose parathyroid hormone [rhPTH (1–34)]. J Oral Maxillofac Surg 65:573–580CrossRefPubMedGoogle Scholar
  100. 100.
    Timurağaoğlu A, Ozkaynak C, Tuzuner S, Bostan F, Undar L (2007) Improvement of zoledronic-acid-induced jaw osteonecrosis with bortezomib. Acta Haematol 118:203–204CrossRefPubMedGoogle Scholar
  101. 101.
    Van den Wyngaert T, Claeys T, Huizing MT, Vermorken JB, Fossion E (2009) Initial experience with conservative treatment in cancer patients with osteonecrosis of the jaw (ONJ) and predictors of outcome. Ann Oncol 20:331–336CrossRefPubMedGoogle Scholar
  102. 102.
    Wimalawansa SJ (2008) Bisphosphonate-associated osteomyelitis of the jaw: guidelines for practicing clinicians. Endocr Pract 14:1150–1168PubMedGoogle Scholar
  103. 103.
    Taylor KH, Middlefell LS, Mizen KD (2010) Osteonecrosis of the jaws induced by anti-RANK ligand therapy. Br J Oral Maxillofac Surg (in press)Google Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2010

Authors and Affiliations

  • Toshiyuki Yoneda
    • 1
  • Hiroshi Hagino
    • 2
  • Toshitsugu Sugimoto
    • 3
  • Hiroaki Ohta
    • 4
  • Shunji Takahashi
    • 5
  • Satoshi Soen
    • 6
  • Akira Taguchi
    • 7
  • Satoru Toyosawa
    • 8
  • Toshihiko Nagata
    • 9
  • Masahiro Urade
    • 10
  1. 1.Department of BiochemistryOsaka University Graduate School of DentistrySuitaJapan
  2. 2.School of Health Science, Faculty of MedicineTottori University HospitalYonagoJapan
  3. 3.Internal Medicine 1Shimane University Faculty of MedicineIzumoJapan
  4. 4.Department of Obstetrics and GynecologyTokyo Women’s Medical UniversityTokyoJapan
  5. 5.Division of Clinical Chemotherapy, Cancer Chemotherapy CenterJapanese Foundation for Cancer ResearchTokyoJapan
  6. 6.Department of Orthopaedic Surgery and Rheumatology, Nara HospitalKinki University School of MedicineNaraJapan
  7. 7.Department of Oral and Maxillofacial RadiologyMatsumoto Dental UniversityShiojiriJapan
  8. 8.Department of Oral PathologyOsaka University Graduate School of DentistryOsakaJapan
  9. 9.Department of Periodontology and Endodontology, Institute of Health BioscienceThe University of Tokushima Graduate SchoolTokushimaJapan
  10. 10.Department of Oral and Maxillofacial SurgeryHyogo College of MedicineHyogoJapan

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