Journal of Oral and Maxillofacial Surgery
Volume 67, Issue 5, Supplement , Pages 96-106 , May 2009

Utility of Hyperbaric Oxygen in Treatment of Bisphosphonate-Related Osteonecrosis of the Jaws

  • John J. Freiberger, MD, MPH

      Affiliations

    • Assistant Professor of Anesthesiology, Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, NC
    • Corresponding Author InformationAddress correspondence and reprint requests to Dr Freiberger: Department of Anesthesiology, Center for Hyperbaric Medicine and Environmental Physiology, Box 3823, Duke University Medical Center, Durham, NC 27710

References 

  1. Feldmeier JJ. Hyperbaric oxygen 2003: Indications and Results—Hyperbaric Oxygen Therapy Committee Report (June 2003). Kensington, MD: Undersea and Hyperbaric Medical Society; 2003;
  2. Mainous EG, Hart GB. Osteoradionecrosis of the mandible: Treatment with hyperbaric oxygen. Arch Otolaryngol. 1975;101:173
  3. Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg. 1983;41:351
  4. Marx RE. Osteoradionecrosis: A new concept of its pathophysiology. J Oral Maxillofac Surg. 1983;41:283
  5. Knighton DR, Halliday B, Hunt TK. Oxygen as an antibiotic: The effect of inspired oxygen on infection. Arch Surg. 1984;119:199
  6. Knighton DR, Fiegel VD, Halverson T, et al. Oxygen as an antibiotic (The effect of inspired oxygen on bacterial clearance). Arch Surg. 1990;125:97
  7. Elayan IM, Axley MJ, Prasad PV, et al. Effect of hyperbaric oxygen treatment on nitric oxide and oxygen free radicals in rat brain. J Neurophysiol. 2000;83:2022
  8. Tandara AA, Mustoe TA. Oxygen in wound healing—More than a nutrient. World J Surg. 2004;28:294
  9. Boykin JV, Baylis C. Hyperbaric oxygen therapy mediates increased nitric oxide production associated with wound healing: A preliminary study. Adv Skin Wound Care. 2007;20:382
  10. Thom SR, Bhopale VM, Velazquez OC, et al. Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol. 2006;290:H1378
  11. Asano T, Kaneko E, Shinozaki S, et al. Hyperbaric oxygen induces basic fibroblast growth factor and hepatocyte growth factor expression, and enhances blood perfusion and muscle regeneration in mouse ischemic hind limbs. Circ J. 2007;71:405
  12. Gallagher KA, Goldstein LJ, Thom SR, et al. Hyperbaric oxygen and bone marrow-derived endothelial progenitor cells in diabetic wound healing. Vascular. 2006;14:328
  13. Gutsaeva DR, Suliman HB, Carraway MS, et al. Oxygen-induced mitochondrial biogenesis in the rat hippocampus. Neuroscience. 2006;137:493
  14. Cabigas BP, Su J, Hutchins W, et al. Hyperoxic and hyperbaric-induced cardioprotection: Role of nitric oxide synthase 3. Cardiovasc Res. 2006;72:143
  15. 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;22:1479
  16. Bedogni A, Blandamura S, Lokmic Z, et al. Bisphosphonate-associated jawbone osteonecrosis: A correlation between imaging techniques and histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:358
  17. Khosa AD, Nayyar MS, Beirne JC. Osteochemonecrosis of jaws and bisphosphonates. Ir Med J. 2007;100:410
  18. Tolar J, Teitelbaum SL, Orchard PJ. Osteopetrosis. N Engl J Med. 2004;351:2839
  19. Lee NK, Choi YG, Baik JY, et al. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood. 2005;106:852
  20. Ha H, Kwak HB, Lee SW, et al. Reactive oxygen species mediate RANK signaling in osteoclasts. Exp Cell Res. 2004;301:119
  21. Bai XC, Lu D, Liu AL, et al. Reactive oxygen species stimulates receptor activator of NF-kappaB ligand expression in osteoblast. J Biol Chem. 2005;280:17497
  22. Hayman AR, Jones SJ, Boyde A, et al. Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis. Development (Cambridge, England). 1996;122:3151
  23. Freiberger JJ, Padilla-Burgos R, Chhoeu AH, et al. Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: A case series. J Oral Maxillofac Surg. 2007;65:1321
  24. Rodan GA, Reszka AA. Bisphosphonate mechanism of action. Curr Mol Med. 2002;2:571
  25. Gutta R, Louis PJ. Bisphosphonates and osteonecrosis of the jaws: Science and rationale. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:186
  26. Matsuo K, Irie N. Osteoclast-osteoblast communication. Arch Biochem Biophys. 2008;473:201
  27. Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev. 2003;4:638
  28. Glantschnig H, Fisher JE, Wesolowski G, et al. M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ. 2003;10:1165
  29. Lehenkari PP, Kellinsalmi M, Napankangas JP, et al. Further insight into mechanism of action of clodronate: Inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002;61:1255
  30. Roelofs AJ, Thompson K, Gordon S, et al. Molecular mechanisms of action of bisphosphonates: Current status. Clin Cancer Res. 2006;12(20 Pt 2):6222s
  31. Benford HL, Frith JC, Auriola S, et al. Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: Biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs. Mol Pharmacol. 1999;56:131
  32. Dunford JE, Thompson K, Coxon FP, et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001;296:235
  33. Coxon FP, Thompson K, Rogers MJ. Recent advances in understanding the mechanism of action of bisphosphonates. Curr Opin Pharmacol. 2006;6:307
  34. Coxon FP, Benford HL, Russell RG, et al. Protein synthesis is required for caspase activation and induction of apoptosis by bisphosphonate drugs. Mol Pharmacol. 1998;54:631
  35. Monkkonen H, Auriola S, Lehenkari P, et al. A new endogenous ATP analog (ApppI) inhibits the mitochondrial adenine nucleotide translocase (ANT) and is responsible for the apoptosis induced by nitrogen-containing bisphosphonates. Br J Pharmacol. 2006;147:437
  36. Kellinsalmi M, Monkkonen H, Monkkonen J, et al. In vitro comparison of clodronate, pamidronate and zoledronic acid effects on rat osteoclasts and human stem cell-derived osteoblasts. Basic Clin Pharmacol Toxicol. 2005;97:382
  37. Van den Wyngaert T, Huizing MT, Vermorken JB. Bisphosphonates and osteonecrosis of the jaw: Cause and effect or a post hoc fallacy?. Ann Oncol. 2006;17:1197
  38. Grotz KA, Walter C, Kuttner C, et al. [Relevance of bisphosphonate long-term therapy in radiation therapy of endosteal jaw metastases]. Strahlenther Onkol. 2007;183:190
  39. Cartsos VM, Zhu S, Zavras AI. Bisphosphonate use and the risk of adverse jaw outcomes: A medical claims study of 714,217 people. J Am Dent Assoc. 2008;139:23
  40. Wilkinson GS, Kuo YF, Freeman JL, et al. Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: A population-based analysis. J Natl Cancer Inst. 2007;99:1016
  41. Khamaisi M, Regev E, Yarom N, et al. Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab. 2007;92:1172
  42. Sarasquete ME, Garcia-Sanz R, Marin L, et al. 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. 2008;112:2709
  43. Iizuka T, Miller SC, Marks SC. Alveolar bone remodeling after tooth extraction in normal and osteopetrotic (ia) rats. J Oral Pathol Med. 1992;21:150
  44. Wang HL, Weber D, McCauley LK. Effect of long-term oral bisphosphonates on implant wound healing: Literature review and a case report. J Periodontol. 2007;78:584
  45. Lam DK, Sandor GK, Holmes HI, et al. A review of bisphosphonate-associated osteonecrosis of the jaws and its management. J Can Dent Assoc. 2007;73:417
  46. Lam DK, Sandor GK, Holmes HI, et al. Marble bone disease: A review of osteopetrosis and its oral health implications for dentists. J Can Dent Assoc. 2007;73:839
  47. Bertoldo F, Santini D, Lo Cascio V. Bisphosphonates and osteomyelitis of the jaw: A pathogenic puzzle. Nat Clin Pract. 2007;4:711
  48. Ruggiero SL, Woo SB. Bisphosphonate-related osteonecrosis of the jaws. Dent Clin North Am. 2008;52:111
  49. Landesberg R, Cozin M, Cremers S, et al. Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg. 2008;66:839
  50. Woo SB, Kalmar JR. Osteonecrosis of the jaws and bisphosphonates. Alpha Omegan. 2007;100:194
  51. Komatsubara S, Mori S, Mashiba T, et al. Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib. J Bone Miner Res. 2004;19:999
  52. Mashiba T. [Assessment of bone quality: Bone quality and osteoporosis treatment]. Clin Calcium. 2008;18:300
  53. Mashiba T, Mori S, Burr DB, et al. The effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. J Bone Miner Metabol. 2005;23(suppl):36
  54. Reid IR, Bolland MJ, Grey AB. Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity?. Bone. 2007;41:318
  55. Demerjian N, Bolla G, Spreux A. Severe oral ulcerations induced by alendronate. Clin Rheumatol. 1999;18:349
  56. Treister NS, Richardson P, Schlossman R, et al. Painful tongue ulcerations in patients with bisphosphonate-associated osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:e1
  57. Schenk R, Eggli P, Fleisch H, et al. Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat. Calcif Tissue Int. 1986;38:342
  58. Adami S, Zamberlan N. Adverse effects of bisphosphonates: A comparative review. Drug Saf. 1996;14:158
  59. Whyte MP, McAlister WH, Novack DV, et al. Bisphosphonate-induced osteopetrosis: Novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases. J Bone Miner Res. 2008;23:1698
  60. Whyte MP, Wenkert D, Clements KL, et al. Bisphosphonate-induced osteopetrosis. N Engl J Med. 2003;349:457
  61. Allegra A, Oteri G, Nastro E, et al. Patients with bisphosphonates-associated osteonecrosis of the jaw have reduced circulating endothelial cells. Hematol Oncol. 2007;25:164
  62. Santini D, Vincenzi B, Avvisati G, et al. Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res. 2002;8:1080
  63. Santini D, Schiavon G, Angeletti S, et al. Last generation of amino-bisphosphonates (N-BPs) and cancer angio-genesis: A new role for these drugs?. Recent Patents on Anti-Cancer Drug Discovery. 2006;1:383
  64. 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. 2005;63:1567
  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 patients—May 2006. Crit Rev Oncol Hematol. 2007;62:148
  66. Nastro E, Musolino C, Allegra A, et al. Bisphosphonate-associated osteonecrosis of the jaw in patients with multiple myeloma and breast cancer. Acta Haematol. 2007;117:181
  67. Krueger CD, West PM, Sargent M, et al. Bisphosphonate-induced osteonecrosis of the jaw. Ann Pharmacother. 2007;41:276
  68. 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;28:158
  69. Migliorati CA, Casiglia J, Epstein J, et al. Managing the care of patients with bisphosphonate-associated osteonecrosis: An American Academy of Oral Medicine position paper. J Am Dent Assoc. 2005;136:1658
  70. Mignogna MD, Fedele S, Lo Russo L, et al. Case 2: Osteonecrosis of the jaws associated with bisphosphonate therapy. J Clin Oncol. 2006;24:1475
  71. Shimura K, Shimazaki C, Taniguchi K, et al. Hyperbaric oxygen in addition to antibiotic therapy is effective for bisphosphonate-induced osteonecrosis of the jaw in a patient with multiple myeloma. Int J Hematol. 2006;84:343
  72. Soileau KM. Oral post-surgical complications following the administration of bisphosphonates given for osteopenia related to malignancy. J Periodontol. 2006;77:738
  73. Kumar SK, Meru M, Sedghizadeh PP. Osteonecrosis of the jaws secondary to bisphosphonate therapy: A case series. J Contemp Dent Pract. 2008;9:63
  74. 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. 2007;33:371
  75. Allen BW, Demchenko IT, Piantadosi CA. Two faces of nitric oxide: implications for cellular mechanisms of oxygen toxicity. J Appl Physiol. 2009;106:662
  76. Piantadosi CA, Tatro LG. Regional H2O2 concentration in rat brain after hyperoxic convulsions. J Appl Physiol. 1990;69:1761
  77. Demchenko IT, Boso AE, O'Neill TJ, et al. Nitric oxide and cerebral blood flow responses to hyperbaric oxygen. J Appl Physiol. 2000;88:1381
  78. Demchenko IT, Boso AE, Whorton AR, et al. Nitric oxide production is enhanced in rat brain before oxygen-induced convulsions. Brain Res. 2001;917:253
  79. Reddy SV. Regulatory mechanisms operative in osteoclasts. Crit Rev Eukaryot Gene Expr. 2004;14:255
  80. van't Hof RJ, Ralston SH. Nitric oxide and bone. Immunology. 2001;103:255
  81. Khosla S. Minireview: The OPG/RANKL/RANK system. Endocrinology. 2001;142:5050
  82. Yu XH, Yang YJ, Wang X, et al. [Effect of hyperbaric oxygenation on neural stem cells and myelin in neonatal rats with hypoxic-ischemic brain damage.]. Zhongguo Dang Dai Er Ke Za Zhi. 2006;8:33
  83. Liu ZJ, Velazquez OC. Hyperoxia, endothelial progenitor cell mobilization, and diabetic wound healing. Antioxid Redox Signal. 2008;10:1869
  84. Fok TC, Jan A, Peel SA, et al. Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:417
  85. Lee CC, Chen SC, Tsai SC, et al. Hyperbaric oxygen induces VEGF expression through ERK, JNK and c-Jun/AP-1 activation in human umbilical vein endothelial cells. J Biomed Sci. 2006;13:143
  86. Peng Z, Ren P, Kang Z, et al. Up-regulated HIF-1alpha is involved in the hypoxic tolerance induced by hyperbaric oxygen preconditioning. Brain Res. 2008;1212:71
  87. Li Z, Liu W, Kang Z, et al. Mechanism of hyperbaric oxygen preconditioning in neonatal hypoxia-ischemia rat model. Brain Res. 2008;1196:151
  88. Yogaratnam JZ, Laden G, Madden LA, et al. Hyperbaric oxygen: A new drug in myocardial revascularization and protection?. Cardiovasc Revasc Med. 2006;7:146
  89. Bianchi SD, Scoletta M, Cassione FB, et al. Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:249
  90. Ikeda F, Nishimura R, Matsubara T, et al. Activation of NFAT signal in vivo leads to osteopenia associated with increased osteoclastogenesis and bone-resorbing activity. J Immunol. 2006;177:2384
  91. Crotti TN, Flannery M, Walsh NC, et al. NFATc1 directly induces the human beta3 integrin gene in osteoclast differentiation. J Musculoskel Neuron Interact. 2005;5:335
  92. Crotti TN, Sharma SM, Fleming JD, et al. PU.1 and NFATc1 mediate osteoclastic induction of the mouse beta3 integrin promoter. J Cell Physiol. 2008;215:636
  93. Tanaka S, Miyazaki T, Fukuda A, et al. Molecular mechanism of the life and death of the osteoclast. Ann NY Acad Sci. 2006;1068:180
  94. Koga T, Matsui Y, Asagiri M, et al. NFAT and Osterix cooperatively regulate bone formation. Nat Med. 2005;11:880
  95. Levy BM, Nelms DC. Migratory inhibition factor associated with chronic destructive periodontitis. J Dent Res. 1971;50:505
  96. Morimoto T, Nishihira J, Kohgo T. Immunohistochemical localization of macrophage migration inhibitory factor (MIF) in human gingival tissue and its pathophysiological functions. Histochem Cell Biol. 2003;120:293

 Novartis Pharmaceuticals Corporation is funding a randomized controlled trial of HBO for BP-associated osteonecrosis of the jaws. Dr Freiberger is the principal investigator.

PII: S0278-2391(08)01829-6

doi: 10.1016/j.joms.2008.12.003

Journal of Oral and Maxillofacial Surgery
Volume 67, Issue 5, Supplement , Pages 96-106 , May 2009