American association of oral and maxillofacial surgeons position paper on medication-related osteonecrosis of the jaw - 2014 update

Journal of Oral and Maxillofacial Surgery

Volumn 72, Issue 10, 2014, Pages 1938-1956

  Ruggiero, Salvatore L ^a   Dodson, Thomas B ^b   Fantasia, John ^c   Goodday, Reginald ^d   Aghaloo, Tara ^e   Mehrotra, Bhoomi ^f   O'Ryan, Felice ^g  

^a Stony Brook Medicine   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c DONALD AND BARBARA ZUCKER SCHOOL OF MEDICINE AT HOFSTRA NORTHWELL   (United States)

^d DALHOUSIE UNIVERSITY   (Canada)

^e UCLA SCHOOL OF DENTISTRY   (United States)

^f ST FRANCIS HOSPITAL   (United States)

^g KAISER PERMANENTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; BEVACIZUMAB; BISPHOSPHONIC ACID DERIVATIVE; CORTICOSTEROID; DENOSUMAB; IBANDRONIC ACID; MONOCLONAL ANTIBODY; PAMIDRONIC ACID; PLACEBO; PROTEIN TYROSINE KINASE INHIBITOR; RAPAMYCIN; SUNITINIB; ZOLEDRONIC ACID; BONE DENSITY CONSERVATION AGENT;

AMERICAN ASSOCIATION OF ORAL AND MAXILLOFACIAL SURGEONS; ANTIANGIOGENIC ACTIVITY; ANTIANGIOGENIC THERAPY; ANTIBIOTIC THERAPY; ARTICLE; BONE REMODELING; CANCER THERAPY; CLINICAL PRACTICE; CLINICAL RESEARCH; CORTICOSTEROID THERAPY; DIAGNOSTIC IMAGING; DIFFERENTIAL DIAGNOSIS; DISEASE SEVERITY; DRUG SAFETY; HEALTH CARE ORGANIZATION; HEALTH CARE PERSONNEL; HEREDITY; HUMAN; HYPERBARIC OXYGEN; INFECTION; INFLAMMATION; JAW OSTEONECROSIS; KNOWLEDGE BASE; MAXILLOFACIAL SURGERY; MEDICAL INFORMATION; MEDICATION RELATED OSTEONECROSIS OF THE JAW; MOUTH DISEASE; MOUTH HYGIENE; ORAL SURGERY; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; PATHOPHYSIOLOGY; PERIODONTAL DISEASE; PRACTICE GUIDELINE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK FACTOR; SOFT TISSUE; SYSTEMATIC REVIEW; TOOTH EXTRACTION; ANGIOGENESIS; BONE NECROSIS; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; JAW DISEASE; NEOPLASM; NOMENCLATURE; PATIENT CARE PLANNING; RISK ASSESSMENT; TIME;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS OF THE JAW; BONE DENSITY CONSERVATION AGENTS; BONE REMODELING; BONE RESORPTION; DIAGNOSIS, DIFFERENTIAL; HUMANS; JAW DISEASES; NEOPLASMS; NEOVASCULARIZATION, PHYSIOLOGIC; ORAL SURGICAL PROCEDURES; OSTEONECROSIS; OSTEOPOROSIS; PATIENT CARE PLANNING; RISK ASSESSMENT; RISK FACTORS; TERMINOLOGY AS TOPIC; TIME FACTORS;

EID: 84909619222     PISSN: 02782391     EISSN: 15315053     Source Type: Journal    
DOI: 10.1016/j.joms.2014.04.031     Document Type: Review

References (184)

1. Ruggiero SL, Dodson TB, Assael LA, et al: American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws-2009 Update. J Oral Maxillofac Surg 67:2, 2009
2. NussbaumSR, Younger J, Vandepol CJ, et al: Single-dose intravenous therapy with pamidronate for the treatment of hypercalcemia of malignancy: Comparison of 30-, 60-, and 90-mg dosages. Am J Med 95:297, 1993
3. Major P, Lortholary A, Hon J, et al: Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: A pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 19:558, 2001
4. Hortobagyi GN, Theriault RL, Porter L, et al: Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 335:1785, 1996
5. 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 16:2038, 1998
6. Hillner BE, Ingle JN, Chlebowski RT, et al: American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21:4042, 2003
7. Saad F, Gleason DM, Murray R, et al: A randomized, placebocontrolled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458, 2002
8. 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 96:879, 2004
9. 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 100:2613, 2004
10. 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 334:488, 1996
11. Berenson JR, Lichtenstein A, Porter L, et al: Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 16:593, 1998
12. 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 7:377, 2001
13. Berenson JR, Hillner BE, Kyle RA, et al: American Society of Clinical Oncology clinical practice guidelines: The role of bisphosphonates in multiple myeloma. J Clin Oncol 20:3719, 2002
14. United States Food and Drug Administration, Center for Drug Evaluation and Research: Drugs @ FDA. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm? CFID=22255647&CFTOKEN=bbf41c75f8cb0109-1F350AA8-A3B1-DF88-62056BCE97C69DB1. Accessed February 10, 2014
15. Physicians' Desk Reference (ed 57). Montvale, NJ, Medical Economics, 2003
16. Delmas PD, Meunier PJ: The management of Paget's disease of bone. N Engl J Med 336:558, 1997
17. Letocha AD, Cintas HL, Troendle JF, et al: Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement. J Bone Miner Res 20:977, 2005
18. Watts NB: Bisphosphonate treatment of osteoporosis. Clin Geriatr Med 19:395, 2003
19. Delmas PD: The use of bisphosphonates in the treatment of osteoporosis. Curr Opin Rheumatol 17:462, 2005
20. Cummings SR, San Martin J, McClung MR, et al: Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756, 2009
21. Papapoulos S, Chapurlat R, Libanati C, et al: Five years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first two years of the FREEDOM extension. J Bone Miner Res 27:694, 2012
22. Fizazi K, Carducci M, Smith M, et al: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A randomised, doubleblind study. Lancet 377:813, 2011
23. Stopeck A, Body JJ, Fujiwara Y, et al: Denosumab versus zolendronic acid for the treatment of breast cancer patients with bone metastases: Results of a randomized phase 3 study. Eur J Cancer 7:2, 2009
24. Marx RE: Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg 61:1115, 2003
25. Ruggiero SL, Mehrotra B, Rosenberg TJ, et al: Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J Oral Maxillofac Surg 62:527, 2004
26. Hohnecker JA:DearDoctor. PrecautionsAddedto the LabelofAredia and Zometa. East Hanover, NJ, Novartis Oncology, 2004. p 2
27. United States Food and Drug Administration, Oncologic Drugs Advisory Committee: Combidex briefing information. Available at: http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4095B1-01-01-AdvancedMag-Combidex.pdf.AccessedFebruary 10, 2014
28. United States Food and Drug Administration, Office of Drug Safety: Postmarketing safety review. Bisphosphonates. Available at: http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4095B2-03-04-FDA-Tab3.pdf. Accessed February 10, 2014
29. Reid IR, Bolland MJ, Grey AB: Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone 41:318, 2007
30. Allen MR, Burr DB: The pathogenesis of bisphosphonaterelated osteonecrosis of the jaw: So many hypotheses, so few data. J Oral Maxillofac Surg 67:61, 2009
31. Landesberg R, Woo V, Cremers S, et al: Potential pathophysiological mechanisms in osteonecrosis of the jaw. Ann N Y Acad Sci 1218:62, 2011
32. Yamashita J, McCauley LK: Antiresorptives and osteonecrosis of the jaw. J Evid Based Dent Pract 12:233, 2012
33. 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 23:8580, 2005
34. Bi Y, Gao Y, Ehirchiou D, et al: Bisphosphonates cause osteonecrosis of the jaw-like disease in mice. Am J Pathol 177:280, 2010
35. Hokugo A, Christensen R, Chung EM, et al: Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats. J Bone Miner Res 25:1337, 2010
36. Mortensen M, Lawson W, Montazem A: Osteonecrosis of the jaw associated with bisphosphonate use: Presentation of seven cases and literature review. Laryngoscope 117:30, 2007
37. Sonis ST, Watkins BA, Lyng GD, et al: 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, 2009
38. Mehrotra B, Ruggiero S: Bisphosphonate complications including osteonecrosis of the jaw. Hematology Am Soc Hematol Educ Program, 2006 356
39. Ruggiero SL, Fantasia J, Carlson E: Bisphosphonate-related osteonecrosis of the jaw: Background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:433, 2006
40. Wood J, Bonjean K, Ruetz S, et al: Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055, 2002
41. BaronR, Ferrari S,Russell RG: Denosumab and bisphosphonates: Different mechanisms of action and effects. Bone 48:677, 2011
42. Lacey DL, Boyle WJ, Simonet WS, et al: Bench to bedside: Elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov 11:401, 2012
43. Russell RG, Watts NB, Ebetino FH, et al: Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 19:733, 2008
44. Roelofs AJ, Thompson K, Gordon S, et al: Molecular mechanisms of action of bisphosphonates: Current status. Clin Cancer Res 12:6222s, 2006
45. Russell RG, Rogers MJ: Bisphosphonates: From the laboratory to the clinic and back again. Bone 25:97, 1999
46. Aghaloo TL, Kang B, Sung EC, et al: Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. J Bone Miner Res 26:1871, 2011
47. Allen MR, Burr DB: Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment. J Oral Maxillofac Surg 66:987, 2008
48. Lipton A, Fizazi K, Stopeck AT, et al: Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 48:3082, 2012
49. Sinningen K, Tsourdi E, Rauner M, et al: Skeletal and extraskeletal actions of denosumab. Endocrine 42:52, 2012
50. Aghaloo TL, Felsenfeld AL, Tetradis S: Osteonecrosis of the jaw in a patient on denosumab. J Oral Maxillofac Surg 68:959, 2010
51. Kuroshima S, Kovacic BL, Kozloff KM, et al: Intra-oral PTH administration promotes tooth extraction socket healing. J Dent Res 92:553, 2013
52. Dayisoylu EH, Senel FC, Ungor C, et al: The effects of adjunctive parathyroid hormone injection on bisphosphonate-related osteonecrosis of the jaws: An animal study. Int J Oral Maxillofac Surg 42:1475, 2013
53. Dimopoulos MA, Kastritis E, Bamia C, et al: 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, 2009
54. Hoff AO, Toth BB, Altundag K, et al: Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23:826, 2008
55. Ripamonti CI, Maniezzo M, Campa T, et al: 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, 2009
56. Boonyapakorn T, Schirmer I, Reichart PA, et al: Bisphosphonateinduced osteonecrosis of the jaws: Prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol 44:857, 2008
57. Marx R: Oral and Intravenous Bisphosphonate Induced Osteonecrosis of the Jaws: History, Etiology, Prevention, and Treatment (ed 2). Hanover Park, IL, Quintessence Publishing, 2011
58. Marx RE, Sawatari Y, Fortin M, et al: Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63:1567, 2005
59. Ficarra G, Beninati F, Rubino I, et al: Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment. J Clin Periodontol 32:1123, 2005
60. Aguirre JI, Akhter MP, Kimmel DB, et al: Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis. J Bone Miner Res 27:2130, 2012
61. Kang B, Cheong S, Chaichanasakul T, et al: Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice. J Bone Miner Res 28:1631, 2013
62. Mawardi H, Treister N, Richardson P, et al: Sinus tracts-An early sign of bisphosphonate-associated osteonecrosis of the jaws? J Oral Maxillofac Surg 67:593, 2009
63. Lopez-Jornet P, Camacho-Alonso F, Martinez-Canovas A, et al: Perioperative antibiotic regimen in rats treated with pamidronate plus dexamethasone and subjected to dental extraction: A study of the changes in the jaws. J Oral Maxillofac Surg 69:2488, 2011
64. Gotcher JE, Jee WS: The progress of the periodontal syndrome in the rice rat. I. Morphometric and autoradiographic studies. J Periodontal Res 16:275, 1981
65. Hansen T, Kunkel M, Weber A, et al: Osteonecrosis of the jaws in patients treated with bisphosphonates-Histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 35:155, 2006
66. Sedghizadeh PP, Kumar SK, Gorur A, et al: Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy. J Oral Maxillofac Surg 66:767, 2008
67. Kos M, Junka A, Smutnicka D, et al: Pamidronate enhances bacterial adhesion to bone hydroxyapatite. Another puzzle in the pathology of bisphosphonate-related osteonecrosis of the jaw? J Oral Maxillofac Surg 71:1010, 2013
68. Sedghizadeh PP, Kumar SK, Gorur A, et al: Microbial biofilms in osteomyelitis of the jaw and osteonecrosis of the jaw secondary to bisphosphonate therapy. J Am Dent Assoc 140:1259, 2009
69. Sedghizadeh PP, Yooseph S, Fadrosh DW, et al: Metagenomic investigation of microbes and viruses in patients with jaw osteonecrosis associated with bisphosphonate therapy. Oral Surg Oral Med Oral Pathol Oral Radiol 114:764, 2012
70. Wanger G, Gorby Y, El-Naggar MY, et al: Electrically conductive bacterial nanowires in bisphosphonate-related osteonecrosis of the jaw biofilms. Oral Surg Oral Med Oral Pathol Oral Radiol 115:71, 2013
71. Kim HK: Introduction to osteonecrosis of the femoral head (OFH) and osteonecrosis of the jaw (ONJ). J Musculoskelet Neuronal Interact 7:350, 2007
72. Bezzi M, Hasmim M, BielerG, et al: Zoledronate sensitizes endothelial cells to tumor necrosis factor-induced programmed cell death: Evidence for the suppression of sustained activation of focal adhesion kinase and protein kinase B/Akt. J Biol Chem 278:43603, 2003
73. Santini D, Vincenzi B, Dicuonzo G, et al: Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res 9:2893, 2003
74. Lin JH: Bisphosphonates: A review of their pharmacokinetic properties. Bone 18:75, 1996
75. Giraudo E, Inoue M, Hanahan D: An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 114:623, 2004
76. Montague R, Hart CA, George NJ, et al: Differential inhibition of invasion and proliferation by bisphosphonates: Antimetastatic potential of zoledronic acid in prostate cancer. Eur Urol 46:389, 2004
77. Landesberg R, Cozin M, Cremers S, et al: Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg 66:839, 2008
78. Reid IR, Cornish J: Epidemiology and pathogenesis of osteonecrosis of the jaw. Nat Rev Rheumatol 8:90, 2012
79. Ali-Erdem M, Burak-Cankaya A, Cemil-Isler S, et al: Extraction socket healing in rats treated with bisphosphonate: Animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patients. Med Oral Patol Oral Cir Bucal 16:e879, 2011
80. Kikuiri T, Kim I, Yamaza T, et al: Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice. J Bone Miner Res 25:1668, 2010
81. Qi WX, Tang LN, He AN, et al: Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: A meta-analysis of seven randomized controlled trials. Int J Clin Oncol 19:403, 2014
82. Coleman R, Woodward E, Brown J, et al: Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer. Breast Cancer Res Treat 127:429, 2011
83. Mauri D, Valachis A, Polyzos IP, et al: Osteonecrosis of the jaw and use of bisphosphonates in adjuvant breast cancer treatment: A meta-analysis. Breast Cancer Res Treat 116:433, 2009
84. Vahtsevanos K, Kyrgidis A, Verrou E, et al: Longitudinal cohort study of risk factors in cancer patients of bisphosphonaterelated osteonecrosis of the jaw. J Clin Oncol 27:5356, 2009
85. Scagliotti GV, Hirsh V, Siena S, et al: Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: Subgroup analysis from a randomized phase 3 study. J Thorac Oncol 7:1823, 2012
86. Guarneri V, MilesD, Robert N, et al: Bevacizumab and osteonecrosis of the jaw: Incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer. Breast Cancer Res Treat 122:181, 2010
87. Lo JC, O'Ryan FS, Gordon NP, et al: Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 68:243, 2010
88. Malden N, Lopes V: An epidemiological study of alendronaterelated osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence. J Bone Miner Metab 30:171, 2012
89. Grbic JT, Black DM, Lyles KW, et al: The incidence of osteonecrosis of the jaw in patients receiving 5 milligrams of zoledronic acid: Data from the health outcomes and reduced incidence with zoledronic acid once yearly clinical trials program. J Am Dent Assoc 141:1365, 2010
90. Henry DH, Costa L, Goldwasser F, et al: Randomized, doubleblind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29:1125, 2011
91. Koch FP, Walter C, Hansen T, et al: Osteonecrosis of the jaw related to sunitinib. J Oral Maxillofac Surg 15:63, 2011
92. Nicolatou-Galitis O, MigkouM, Psyrri A, et al: Gingival bleeding and jawbone necrosis in patients with metastatic renal cell carcinoma receiving sunitinib: Report of 2 cases with clinical implications. Oral Surg Oral Med Oral Pathol Oral Radiol 113:234, 2012
93. Fleissig Y, Regev E, Lehman H: Sunitinib related osteonecrosis of jaw: A case report. Oral Surg Oral Med Oral Pathol Oral Radiol 113:e1, 2012
94. Brunello A, Saia G, Bedogni A, et al:Worsening of osteonecrosis of the jaw during treatment with sunitinib in a patient with metastatic renal cell carcinoma. Bone 44:173, 2009
95. Ayllon J, Launay-Vacher V, Medioni J, et al: Osteonecrosis of the jaw under bisphosphonate and antiangiogenic therapies: Cumulative toxicity profile? Ann Oncol 20:600, 2009
96. Christodoulou C, Pervena A, Klouvas G, et al: Combination of bisphosphonates and antiangiogenic factors induces osteonecrosis of the jaw more frequently than bisphosphonates alone. Oncology 76:209, 2009
97. Balmor GR, Yarom N, Weitzen R: Drug-induced palate osteonecrosis following nasal surgery. Isr Med Assoc J 14:193, 2012
98. Hoefert S, Eufinger H: Sunitinib may raise the risk of bisphosphonate-related osteonecrosis of the jaw: Presentation of three cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:463, 2010
99. Bozas G, Roy A, Ramasamy V, et al: Osteonecrosis of the jaw after a single bisphosphonate infusion in a patient with metastatic renal cancer treated with sunitinib. Onkologie 33:321, 2010
100. Beuselinck B,WolterP,KaradimouA, et al:Concomitantoral tyrosine kinase inhibitors and bisphosphonates in advanced renal cell carcinomawith bonemetastases. Br JCancer107:1665, 2012
101. Smidt-Hansen T, Folkmar TB, Fode K, et al: Combination of zoledronic acid and targeted therapy is active but may induce osteonecrosis of the jaw in patients with metastatic renal cell carcinoma. J Oral Maxillofac Surg 71:1532, 2013
102. United States Food and Drug Administration: Avastin (bevacizumab) safety information. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm275758.htm. Accessed March 13, 2014
103. United States Food and Drug Administration: Sutent (sunitinib malate) capsules. Safety information. Available at: http://www. fda.gov/safety/medwatch/safetyinformation/ucm224050.htm. Accessed March 13, 2014
104. United States Food and Drug Administration: Background document for meeting of advisory committee for reproductive health drugs and drug safety and risk management advisory committee. September 9, 2011. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/drugs/DrugSafetyandRiskManagementAdvisoryCommittee/ucm270958.pdf. Accessed February 10, 2014
105. Felsenberg D, Hoffmeister B: [Necrosis of the jaw after highdose bisphosphonate therapy]. Dtsch Arztebl 103:3078 (in German), 2006.
106. Black DM, Reid IR, Boonen S, et al: The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243, 2012
107. United States Food and Drug Administration: Briefing information for the September 9, 2011 joint meeting of the reproductive health drugs advisory committee and the drug safety and risk management advisory committee. September 9, 2011. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/ucm270957.htm. Accessed April 7, 2014
108. Saad F, Brown JE, Van Poznak C, et al: Incidence, risk factors, and outcomes of osteonecrosis of the jaw: Integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol 23:1341, 2012
109. Fehm T, Beck V, Banys M, et al: Bisphosphonate-induced osteonecrosis of the jaw(ONJ): Incidence and risk factors in patients with breast cancer and gynecological malignancies. Gynecol Oncol 112:605, 2009
110. Kyrgidis A, Vahtsevanos K, Koloutsos G, et al: Bisphospho-nate-related osteonecrosis of the jaws: A case-control study of risk factors in breast cancer patients. J Clin Oncol 26:4634, 2008
111. Kunchur R, Need A, Hughes T, et al: Clinical investigation of C-terminal cross-linking telopeptide test in prevention and management of bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg 67:1167, 2009
112. Yamazaki T, Yamori M, Ishizaki T, et al: Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: A cohort study. Int J Oral Maxillofac Surg 41:1397, 2012
113. Mozzati M, Arata V, Gallesio G: Tooth extraction in patients on zoledronic acid therapy. Oral Oncol 48:817, 2012
114. Scoletta M, Arata V, Arduino PG, et al: Tooth extractions in intravenous bisphosphonate-treated patients: A refined protocol. J Oral Maxillofac Surg 71:994, 2013
115. Tsao C, Darby I, Ebeling PR, et al: Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. J Oral Maxillofac Surg 71:1360, 2013
116. Brown JJ, Ramalingam L, Zacharin MR: Bisphosphonateassociated osteonecrosis of the jaw: Does it occur in children? Clin Endocrinol (Oxf) 68:863, 2008
117. Katz J, Gong Y, Salmasinia D, et al: Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J Oral Maxillofac Surg 40:605, 2011
118. Nicoletti P, Cartsos VM, Palaska PK, et al: Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: The role of RBMS3. Oncologist 17:279, 2012
119. Marini F, Tonelli P, Cavalli L, et al: Pharmacogenetics of bisphosphonate-associated osteonecrosis of the jaw. Front Biosci (Elite Ed) 3:364, 2011
120. Sivolella S, Lumachi F, Stellini E, et al: Denosumab and antiangiogenetic drug-related osteonecrosis of the jaw: An uncommon but potentially severe disease. Anticancer Res 33:1793, 2013
121. Epstein MS, Epstein JB, Ephros HD: The effects of osteoclast modifiers on the oral cavity: A review for prescribers. Curr Opin Support Palliat Care 6:337, 2012
122. Vescovi P, Merigo E, Meleti M, et al: Bisphosphonates-related osteonecrosis of the jaws: A concise review of the literature and a report of a single-centre experience with 151 patients. J Oral Pathol Med 41:214, 2012
123. Schubert M, Klatte I, LinekW, et al: The Saxon bisphosphonate register-Therapy and prevention of bisphosphonate-related osteonecrosis of the jaws. Oral Oncol 48:349, 2012
124. Shannon J, Shannon J, Modelevsky S, et al: Bisphosphonates and osteonecrosis of the jaw. J Am Geriatr Soc 59:2350, 2011
125. Lo JC, O'Ryan F, Yang J, et al: Oral health considerations in older women receiving oral bisphosphonate therapy. J Am Geriatr Soc 59:916, 2011
126. Hellstein JW, Adler RA, Edwards B, et al: Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: Executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 142:1243, 2011
127. Patel V, McLeod NM, Rogers SN, et al: Bisphosphonate osteonecrosis of the jaw-A literature review of UK policies versus international policies on bisphosphonates, risk factors and prevention. Br J Oral Maxillofac Surg 49:251, 2011
128. Atalay B, Yalcin S, Emes Y, et al: Bisphosphonate-related osteonecrosis: Laser-assisted surgical treatment or conventional surgery? Lasers Med Sci 26:815, 2011
129. Aapro M, Saad F, Costa L: Optimizing clinical benefits of bisphosphonates in cancer patients with bone metastases. Oncologist 15:1147, 2010
130. Fehm T, Felsenberg D, Krimmel M, et al: Bisphosphonateassociated osteonecrosis of the jaw in breast cancer patients: Recommendations for prevention and treatment. Breast 18:213, 2009
131. Walter C, Al-Nawas B, du Bois A, et al: Incidence of bisphosphonate-associated osteonecrosis of the jaws in breast cancer patients. Cancer 115:1631, 2009
132. Khan AA, Sandor GK, Dore E, et al: Bisphosphonate associated osteonecrosis of the jaw. J Rheumatol 36:478, 2009
133. Dickinson M, Prince HM, Kirsa S, et al: Osteonecrosis of the jaw complicating bisphosphonate treatment for bone disease in multiple myeloma: An overview with recommendations for prevention and treatment. Intern Med J 39:304, 2009
134. Edwards BJ, Hellstein JW, Jacobsen PL, et al: 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, 2008
135. Abu-Id MH,Warnke PH, Gottschalk J, et al: "Bis-phossy jaws"-High and low risk factors for bisphosphonate-induced osteonecrosis of the jaw. J Craniomaxillofac Surg 36:95, 2008
136. 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 25:2464, 2007
137. Bonacina R, Mariani U, Villa F, et al: Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: A review of 282 patients. J Can Dent Assoc 77:b147, 2011
138. Vandone AM, Donadio M, Mozzati M, et al: Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: A single-center clinical experience. Ann Oncol 23:193, 2012
139. Hinchy NV, Jayaprakash V, Rossitto RA, et al: Osteonecrosis of the jaw-Prevention and treatment strategies for oral health professionals. Oral Oncol 49:878, 2013
140. Khan AA, Morrison A, Hanley DA, et al: International consensus on diagnosis and management of osteonecrosis of the jaw. J Bone Miner Res:22, 2013
141. Damm DD, Jones DM: Bisphosphonate-related osteonecrosis of the jaws: A potential alternative to drug holidays. Gen Dent 61:33, 2013
142. Durie BG, Katz M, Crowley J: Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99, 2005
143. Hoff AO, Toth BB, Altundag K, et al: Osteonecrosis of the jawin patients receiving intravenous bisphosphonate therapy. J Clin Oncol 24:8528, 2006
144. Badros A,Weikel D, Salama A, et al: Osteonecrosis of the jaw in multiple myeloma patients: Clinical features and risk factors. J Clin Oncol 24:945, 2006
145. Mehrotra B, Fantasia J, Ruggiero SL: Outcomes of bisphosphonate related osteonecrosis of the jaw. Importance of staging and management. A large single institution update. J Clin Oncol 26:20526, 2008
146. Endodontic Implications of Bisphosphonate-Associated Osteonecrosis of the Jaws. Chicago, IL, American Association of Endodontists, 2010. p 4
147. Marx RE, Cillo JE Jr, Ulloa JJ: Oral bisphosphonate-induced osteonecrosis: Risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 65:2397, 2007
148. Carlson ER, Basile JD: The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67:85, 2009
149. Bagan JV, Jimenez Y, Gomez D, et al: Collagen telopeptide (serum CTX) and its relationship with the size and number of lesions in osteonecrosis of the jaws in cancer patients on intravenous bisphosphonates. Oral Oncol 44:1088, 2008
150. Kwon YD, Kim DY, Ohe JY, et al: Correlation between serum Cterminal cross-linking telopeptide of type I collagen and staging of oral bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67:2644, 2009
151. Lehrer S, Montazem A, Ramanathan L, et al: Normal serum bone markers in bisphosphonate-induced osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106:389, 2008
152. Migliorati CA, Saunders D, Conlon MS, et al: Assessing the association between bisphosphonate exposure and delayed mucosal healing after tooth extraction. J Am Dent Assoc 144:406, 2013
153. Fleisher KE, Welch G, Kottal S, et al: Predicting risk for bisphosphonate-related osteonecrosis of the jaws: CTX versus radiographic markers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:509, 2010
154. Rosen HN, Moses AC, Garber J, et al: Serum CTX: A new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 66:100, 2000
155. Kim I, Ki H, LeeW, et al: The effect of systemically administered bisphosphonates on bony healing after tooth extraction and osseointegration of dental implants in the rabbit maxilla. Int J Oral Maxillofac Implants 28:1194, 2013
156. Graziani F, Vescovi P, Campisi G, et al: Resective surgical approach shows a high performance in the management of advanced cases of bisphosphonate-related osteonecrosis of the jaws: A retrospective survey of 347 cases. J Oral Maxillofac Surg 70:2501, 2012
157. Stanton DC, Balasanian E: Outcome of surgical management of bisphosphonate-related osteonecrosis of the jaws: Review of 33 surgical cases. J Oral Maxillofac Surg 67:943, 2009
158. Stockmann P, Vairaktaris E,Wehrhan F, et al: Osteotomy and primary wound closure in bisphosphonate-associated osteonecrosis of the jaw: A prospective clinical study with 12 months follow-up. Support Care Cancer 18:449, 2010
159. Mucke T, Koschinski J, Deppe H, et al: Outcome of treatment and parameters influencing recurrence in patients with bisphosphonate-related osteonecrosis of the jaws. J Cancer Res Clin Oncol 137:907, 2011
160. Eckardt AM, Lemound J, Lindhorst D, et al: Surgical management of bisphosphonate-related osteonecrosis of the jaw in oncologic patients: A challenging problem. Anticancer Res 31:2313, 2011
161. Ferlito S, Puzzo S, Palermo F, et al: Treatment of bisphosphonate-related osteonecrosis of the jaws: Presentation of a protocol and an observational longitudinal study of an Italian series of cases. Br J Oral Maxillofac Surg 50:425, 2012
162. Saussez S, Javadian R, Hupin C, et al: Bisphosphonate-related osteonecrosis of the jaw and its associated risk factors: A Belgian case series. Laryngoscope 119:323, 2009
163. Scoletta M, Arduino PG, Dalmasso P, et al: Treatment outcomes in patients with bisphosphonate-related osteonecrosis of the jaws: A prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:46, 2010
164. Van den Wyngaert T, Claeys T, Huizing MT, et al: Initial experience with conservative treatment in cancer patients with osteonecrosis of the jaw (ONJ) and predictors of outcome. Ann Oncol 20:331, 2009
165. Wutzl A, Biedermann E,Wanschitz F, et al: Treatment results of bisphosphonate-related osteonecrosis of the jaws. Head Neck 30:1224, 2008
166. Kademani D, Koka S, Lacy MQ, et al: Primary surgical therapy for osteonecrosis of the jawsecondary to bisphosphonate therapy. Mayo Clin Proc 81:1100, 2006
167. Freiberger JJ, Padilla-Burgos R, McGrawT, et al: What is the role of hyperbaric oxygen in the management of bisphosphonaterelated osteonecrosis of the jaw: A randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics. J Oral Maxillofac Surg 70:1573, 2012
168. Freiberger JJ: Utility of hyperbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67:96, 2009
169. Lee CY, David T, Nishime M: Use of platelet-rich plasma in the management of oral biphosphonate-associated osteonecrosis of the jaw: A report of 2 cases. J Oral Implantol 33:371, 2007
170. Soydan SS, Uckan S: Management of bisphosphonate-related osteonecrosis of the jaw with a platelet-rich fibrin membrane: Technical report. J Oral Maxillofac Surg 72:322, 2014
171. Scoletta M, Arduino PG, Reggio L, et al: Effect of low-level laser irradiation on bisphosphonate-induced osteonecrosis of the jaws: Preliminary results of a prospective study. Photomed Laser Surg 28:179, 2010
172. Vescovi P, Merigo E, Manfredi M, et al: Nd:YAG laser biostimulation in the treatment of bisphosphonate-associated osteonecrosis of the jaw: Clinical experience in 28 cases. Photomed Laser Surg 26:37, 2008
173. Bashutski JD, Eber RM, Kinney JS, et al: Teriparatide and osseous regeneration in the oral cavity. N Engl J Med 363:2396, 2010
174. Gerard DA, Carlson ER, Gotcher JE, et al: Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein. J Oral Maxillofac Surg 72:61, 2014
175. Fedele S, Porter SR, D'Aiuto F, et al: Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: A case series. Am J Med 123:1060, 2010
176. O'Ryan FS, Khoury S, LiaoW, et al: Intravenous bisphosphonaterelated osteonecrosis of the jaw: Bone scintigraphy as an early indicator. J Oral Maxillofac Surg 67:1363, 2009
177. Bedogni A, Fusco V, Agrillo A, et al: Learning from experience. Proposal of a refined definition and staging system for bisphosphonate-related osteonecrosis of the jaw (BRONJ). Oral Dis 18:621, 2012
178. Schiodt M, Reibel J, Oturai P, et al: Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the jaws: A retrospective analysis from the Copenhagen cohort and a proposal for an updated classification system. Oral Surg Oral Med Oral Pathol Oral Radiol 117:204, 2014
179. Kumar SK, Gorur A, Schaudinn C, et al: The role of microbial biofilms in osteonecrosis of the jaw associated with bisphosphonate therapy. Curr Osteoporos Rep 8:40, 2010
180. Engroff SL, Kim DD: Treating bisphosphonate osteonecrosis of the jaws: Is there a role for resection and vascularized reconstruction? J Oral Maxillofac Surg 65:2374, 2007
181. Ferrari S, Bianchi B, Savi A, et al: Fibula free flap with endosseous implants for reconstructing a resected mandible in bisphosphonate osteonecrosis. J Oral Maxillofac Surg 66:999, 2008
182. Seth R, FutranND,AlamDS, et al:Outcomes of vascularized bone graft reconstruction of the mandible in bisphosphonate-related osteonecrosis of the jaws. Laryngoscope 120:2165, 2010
183. Carlson ER, Fleisher KE, Ruggiero SL: Metastatic cancer identified in osteonecrosis specimens of the jaws in patients receiving intravenous bisphosphonate medications. J Oral Maxillofac Surg 71:2077, 2013
184. United States National Institutes of Health: Funding opportunities and notices search results. Available at: http://grants.nih.gov/grants/guide/search-results.htm?text-curr=osteonecrosis&scope=pa-rfa&year=active&sort=&Search.x=10&Search.y=8.Accessed February 10, 2014