Journal of Cranio-Maxillo-Facial Surgery
Volume 39, Issue 4 , Pages 272-277 , June 2011

Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: Not just a sporadic coincidence – a multi-centre study

  • Sven Otto

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Michael Ehrenfeld), University of Munich, Lindwurmstr. 2a, D-80336 Munich, Germany
  • ,
  • Mario Hakim Abu-Id

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Thomas Kreusch), Asklepios Klinik Nord – Heidberg, Tangstedter Landstr. 400, D-22417 Hamburg, Germany
  • ,
  • Stefano Fedele

      Affiliations

    • Department of Oral Medicine (Head of Department: Prof. Stephen Porter), UCL Eastman Dental Institute, 256 Gray’s Inn Road, WC1X 8LD London, UK
  • ,
  • Patrick H. Warnke

      Affiliations

    • Faculty of Health Sciences and Medicine (Chair of Surgery: Prof. Dr. Dr. Patrick H. Warnke), Bond University, Gold Coast, Queensland 4229, Australia
  • ,
  • Stephan T. Becker

      Affiliations

    • Department of Oral and Maxillofacial and Facial Plastic Surgery (Head of Department: Prof. Dr. Dr. Jörg Wiltfang), University of Kiel, Arnold-Heller-Strasse 16, D-24105 Kiel, Germany
  • ,
  • Andreas Kolk

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Klaus-Dietrich Wolff), Technische Universität München, Ismaninger Str. 22, D-81675 Munich, Germany
  • ,
  • Thomas Mücke

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Klaus-Dietrich Wolff), Technische Universität München, Ismaninger Str. 22, D-81675 Munich, Germany
    • Department of Oral and Maxillofacial Plastic Surgery (Prof. Dr. Dr. Martin Kunkel succeeded Prof. Dr. Dr. Klaus-Dietrich Wolff as Head of Department in Feb 2008), Ruhr-University Bochum, Knappschaftskrankenhaus Bochum-Langendreer, D- 44892 Bochum, Germany
  • ,
  • Gerson Mast

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Michael Ehrenfeld), University of Munich, Lindwurmstr. 2a, D-80336 Munich, Germany
  • ,
  • Robert Köhnke

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prim. Univ.-Doz. DDr. Oliver Ploder), Landeskrankenhaus Feldkirch, A-6807 Feldkirch, Austria
  • ,
  • Elias Volkmer

      Affiliations

    • Experimental Surgery and Regenerative Medicine, Department of Surgery (Head of Department: Prof. Dr. Matthias Schieker), University of Munich, Nussbaumstraße 20, D-80336 Munich, Germany
  • ,
  • Florian Haasters

      Affiliations

    • Experimental Surgery and Regenerative Medicine, Department of Surgery (Head of Department: Prof. Dr. Matthias Schieker), University of Munich, Nussbaumstraße 20, D-80336 Munich, Germany
  • ,
  • Olivier Lieger

      Affiliations

    • Department of Cranio-Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Tateyuki Iizuka), University of Bern, Inselspital, CH-3010 Bern, Switzerland
  • ,
  • Tateyuki Iizuka

      Affiliations

    • Department of Cranio-Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Tateyuki Iizuka), University of Bern, Inselspital, CH-3010 Bern, Switzerland
  • ,
  • Stephen Porter

      Affiliations

    • Department of Oral Medicine (Head of Department: Prof. Stephen Porter), UCL Eastman Dental Institute, 256 Gray’s Inn Road, WC1X 8LD London, UK
  • ,
  • Giuseppina Campisi

      Affiliations

    • Department of Oral Sciences (Head of Department: Prof. Messina Pietro), University of Palermo, Via del Vespro 129, 90127 Palermo, Italy
  • ,
  • Giuseppe Colella

      Affiliations

    • Department of Head and Neck Surgery (Head of Department: Prof. Sergio Tartaro), Second University of Naples, Piazza Miraglia, 80100 Naples, Italy
  • ,
  • Oliver Ploder

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prim. Univ.-Doz. DDr. Oliver Ploder), Landeskrankenhaus Feldkirch, A-6807 Feldkirch, Austria
  • ,
  • Andreas Neff

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Andreas Neff), University of Marburg, Georg-Voigt-Straße 3, D-35039 Marburg, Germany
  • ,
  • Jörg Wiltfang

      Affiliations

    • Department of Oral and Maxillofacial and Facial Plastic Surgery (Head of Department: Prof. Dr. Dr. Jörg Wiltfang), University of Kiel, Arnold-Heller-Strasse 16, D-24105 Kiel, Germany
  • ,
  • Michael Ehrenfeld

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Michael Ehrenfeld), University of Munich, Lindwurmstr. 2a, D-80336 Munich, Germany
  • ,
  • Thomas Kreusch

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Thomas Kreusch), Asklepios Klinik Nord – Heidberg, Tangstedter Landstr. 400, D-22417 Hamburg, Germany
  • ,
  • Klaus-Dietrich Wolff

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Klaus-Dietrich Wolff), Technische Universität München, Ismaninger Str. 22, D-81675 Munich, Germany
    • Department of Oral and Maxillofacial Plastic Surgery (Prof. Dr. Dr. Martin Kunkel succeeded Prof. Dr. Dr. Klaus-Dietrich Wolff as Head of Department in Feb 2008), Ruhr-University Bochum, Knappschaftskrankenhaus Bochum-Langendreer, D- 44892 Bochum, Germany
  • ,
  • Stephen R. Stürzenbaum

      Affiliations

    • Pharmaceutical Science Division (Head of Department: Prof. Frank Kelly), King’s College London, London SE1 9NH, UK
  • ,
  • Matthias Schieker

      Affiliations

    • Experimental Surgery and Regenerative Medicine, Department of Surgery (Head of Department: Prof. Dr. Matthias Schieker), University of Munich, Nussbaumstraße 20, D-80336 Munich, Germany
  • ,
  • Christoph Pautke

      Affiliations

    • Department of Oral and Maxillofacial Surgery (Head of Department: Prof. Dr. Dr. Michael Ehrenfeld), University of Munich, Lindwurmstr. 2a, D-80336 Munich, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 (0) 89 5160 2919; Fax: +49 (0) 89 5160 4743.

Received 7 February 2010 ,Accepted 20 May 2010.

References 

  1. AACE . American Association of Clinical Endocrinologists: medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis. 2001 Edition, with selected updates for 2003 http://www.aace.com/pub/pdf/guidelines/osteoporosis2001Revised.pdf
  2. AAOMFS . American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007;65:369–376
  3. Abu-Id MH, Acil Y, Gottschalk J, Kreusch T. Bisphosphonate-associated osteonecrosis of the jaw, Mund Kiefer Gesichtschir. 2006;10:73–81
  4. Abu-Id MH, Warnke PH, Gottschalk J, Springer I, Wiltfang J, Acil Y, et al. “Bis-phossy jaws” – high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw. J Craniomaxillofac Surg. 2008;36:95–103
  5. Aghaloo TL, Felsenfeld AL, Tetradis S. Osteonecrosis of the jaw in a patient on Denosumab. J Oral Maxillofac Surg. 2010;68:959–963
  6. Badros A, Terpos E, Katodritou E, Goloubeva O, Kastritis E, Verrou E, et al. Natural history of osteonecrosis of the jaw in patients with multiple myeloma. J Clin Oncol. 2008;26:5904–5909
  7. Badros A, Weikel D, Salama A, Goloubeva O, Schneider A, Rapoport A, et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol. 2006;24:945–952
  8. Baim S, Miller PD. 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. 2009;24:561–574
  9. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol. 2005;23:8580–8587
  10. Berenson JR, Hillner BE, Kyle RA, Anderson K, Lipton A, Yee GC, et al. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol. 2002;20:3719–3736
  11. Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med. 1996;334:488–493
  12. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535–1541
  13. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296:2927–2938
  14. Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:1189–1199
  15. Boonyapakorn T, Schirmer I, Reichart PA, Sturm I, Massenkeil G. Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol. 2008;44:857–869
  16. Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest. 1997;100:1475–1480
  17. Corso A, Varettoni M, Zappasodi P, Klersy C, Mangiacavalli S, Pica G, et al. A different schedule of zoledronic acid can reduce the risk of the osteonecrosis of the jaw in patients with multiple myeloma. Leukemia. 2007;21:1545–1548
  18. Cranney A, Tugwell P, Adachi J, Weaver B, Zytaruk N, Papaioannou A, et al. Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev. 2002;23:517–523
  19. Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos LA, et al. Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica. 2006;91:968–971
  20. Dimopoulos MA, Kastritis E, Bamia C, Melakopoulos I, Gika D, Roussou M, 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. 2009;20:117–120
  21. DVO-Guideline for Prevention, Clinical assesssment and treatment of osteoporosis for women after menopause, for men after age 60. Schattauer GmbH, Germany, 2006 http://www.lutherhaus.de/osteo/leitlinien-dvo/english.php?aufklappen=RW5nbGlzY2hlIFZlcnNpb24gJ
  22. Engroff SL, Kim DD. Treating bisphosphonate osteonecrosis of the jaws: is there a role for resection and vascularized reconstruction?. J Oral Maxillofac Surg. 2007;65:2374–2385
  23. Farrugia MC, Summerlin DJ, Krowiak E, Huntley T, Freeman S, Borrowdale R, et al. Osteonecrosis of the mandible or maxilla associated with the use of new generation bisphosphonates. Laryngoscope. 2006;116:115–120
  24. Hess LM, Jeter JM, Benham-Hutchins M, Alberts DS. Factors associated with osteonecrosis of the jaw among bisphosphonate users. Am J Med. e3, 2008;121:475–483
  25. Hong JW, Nam W, Cha IH, Chung SW, Choi HS, Kim KM, et al. Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia. Osteoporos Int. 2009;
  26. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, 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;22:1479–1491
  27. King AE, Umland EM. Osteonecrosis of the jaw in patients receiving intravenous or oral bisphosphonates. Pharmacotherapy. 2008;28:667–677
  28. Kyle RA, Yee GC, Somerfield MR, Flynn PJ, Halabi S, Jagannath S, et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol. 2007;25:2464–2472
  29. Kyrgidis A, Vahtsevanos K, Koloutsos G, Andreadis C, Boukovinas I, Teleioudis Z, et al. Bisphosphonate-related osteonecrosis of the jaws: a case–control study of risk factors in breast cancer patients. J Clin Oncol. 2008;26:4634–4638
  30. Lo JC, O’ryan FS, Gordon NP, Yang J, Hui RL, Martin D, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg. 2010;68:243–253
  31. Markose G, Mackenzie FR, Currie WJ, Hislop WS. Bisphosphonate osteonecrosis: a protocol for surgical management. Br J Oral Maxillofac Surg. 2009;47:294–297
  32. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61:1115–1117
  33. Marx RE, Cillo JE, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 2007;65:2397–2410
  34. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63:1567–1575
  35. McLeod NM, Davies BJ, Brennan PA. Bisphosphonate osteonecrosis of the jaws; an increasing problem for the dental practitioner. Br Dent J. 2007;203:641–644
  36. Migliorati CA. Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol. 2003;21:4253–4254
  37. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006;7:508–514
  38. Mücke T, Haarmann S, Wolff KD, Hölzle F. Bisphosphonate related osteonecrosis of the jaws treated by surgical resection and immediate osseous microvascular reconstruction. J Craniomaxillofacial Surg. 2009;37:291–297
  39. Otto S, Hafner S, Grotz KA. The role of inferior alveolar nerve involvement in bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg. 2009;67:589–592
  40. Pautke C, Bauer F, Bissinger O, Tischer T, Kreutzer K, Steiner T, et al. Tetracycline bone fluorescence: a valuable marker for osteonecrosis characterization and therapy. J Oral Maxillofac Surg. 2010;68:125–129
  41. Pautke C, Bauer F, Tischer T, Kreutzer K, Weitz J, Kesting M, et al. Fluorescence-guided bone resection in bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg. 2009;67:471–476
  42. Pazianas M, Blumentals WA, Miller PD. Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int. 2008;19:773–779
  43. Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther. 2007;29:1548–1558
  44. Piesold JU, Al-Nawas B, Grotz KA. Osteonecrosis of the jaws by long term therapy with bisphosphonates, Mund Kiefer Gesichtschir. 2006;10:287–300
  45. Rizzoli R, Burlet N, Cahall D, Delmas PD, Eriksen EF, Felsenberg D, et al. Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis. Bone. 2008;42:841–847
  46. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws – 2009 update. J Oral Maxillofac Surg. 2009;67:2–12
  47. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004;62:527–534
  48. Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367:2010–2018
  49. Silverman SL, Landesberg R. Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. Am J Med. 2009;122:S33–S45
  50. Taylor KH, Middlefell LS, Mizen KD. Osteonecrosis of the jaws induced by anti-RANK ligand therapy. Br J Oral Maxillofac Surg. 2009;
  51. Walter C, Al-Nawas B, Grotz KA, Thomas C, Thuroff JW, Zinser V, et al. Prevalence and risk factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer patients with advanced disease treated with zoledronate. Eur Urol. 2008;54:1066–1072
  52. Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg. 2007;65:1328–1331
  53. Wang J, Goodger NM, Pogrel MA. Osteonecrosis of the jaws associated with cancer chemotherapy. J Oral Maxillofac Surg. 2003;61:1104–1107
  54. Yarom N, Yahalom R, Shoshani Y, Hamed W, Regev E, Elad S. Osteonecrosis of the jaw induced by orally administered bisphosphonates: incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int. 2007;18:1363–1370

 The study was not supported by research grants or any other sources.

PII: S1010-5182(10)00130-7

doi: 10.1016/j.jcms.2010.05.009

Journal of Cranio-Maxillo-Facial Surgery
Volume 39, Issue 4 , Pages 272-277 , June 2011