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Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015

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Abstract

Osteonecrosis of the jaw (ONJ) has been associated with the use of aminobisphosphonates and denosumab. The vast majority (>90 %) of cases occur in the oncology patient population receiving high doses of intravenous bisphosphonates or subcutaneous denosumab. The incidence of ONJ in the osteoporosis patient population is very low and is estimated at 1–90 per 100,000 patient-years of exposure. In the oncology patient population the incidence appears to be related to dose and duration of exposure, and prevalence has been estimated to be as high as 18.6 %. A number of risk factors in addition to antiresorptive therapy have been identified. These include the presence of periodontal disease, oral surgical procedures with extractions or implants, radiation therapy, chemotherapy, diabetes, glucocorticoid use, and smoking. Antiangiogenic agents appear to contribute to the risk of ONJ, however, data at this time are limited and further evidence is required prior to confirming a causal relationship. ONJ may be prevented with optimization of oral hygiene, the use of oral antimicrobial mouth rinses, as well as systemic antibiotic therapy. Individuals not responding to conservative management or in the advanced stages of ONJ may be considered for surgery, as data over the past several years have demonstrated surgical success in this patient population. Case reports have indicated that teriparatide may enhance healing. A number of experimental therapies are being evaluated and include the use of bone marrow stem cell intralesional transplantation, local application of platelet-derived growth factor, hyperbaric oxygen, tissue grafting, and low-level laser therapy. This paper summarizes the current research as well as the international consensus on the diagnosis and management of ONJ.

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References

  1. Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–7

    Article  PubMed  Google Scholar 

  2. Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F et al (2015) Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. JBMR 30:3–23

    Article  Google Scholar 

  3. Fedele S, Porter SR, D'Aiuto F, Aljohani S, Vescovi P, Manfredi M et al (2010) Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. Am J Med 123:1060–4

    Article  CAS  PubMed  Google Scholar 

  4. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B et al (2014) American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw - 2014 update. J Oral Maxillofac Surg 72(10):1938–56

    Article  PubMed  Google Scholar 

  5. 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 65:415–23

    Article  PubMed  Google Scholar 

  6. Khan AA, Rios LP, Sandor GK, Khan N, Peters E, Rahman MO et al (2011) Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons. J Rheumatol 38:1396–402

    Article  CAS  PubMed  Google Scholar 

  7. Ulmner M, Jarnbring F, Torring O (2014) Osteonecrosis of the jaw in Sweden associated with the oral use of bisphosphonate. J Oral Maxillofac Surg 72:76–82

    Article  PubMed  Google Scholar 

  8. Etminan M, Aminzadeh K, Matthew IR, Brophy JM (2008) Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case-control study. J Rheumatol 35:691–5

    CAS  PubMed  Google Scholar 

  9. Tennis P, Rothman KJ, Bohn RL, Tan H, Zavras A, Laskarides C et al (2012) Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis. Pharmacoepidemiol Drug Saf 21:810–7

    Article  CAS  PubMed  Google Scholar 

  10. Grbic JT, Landesberg R, Lin SQ, Mesenbrink P, Reid IR, Leung PC et al (2008) Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yearly pivotal fracture trial. J Am Dent Assoc 139:32–40

    Article  CAS  PubMed  Google Scholar 

  11. Devogelaer JP, Brown JP, Burckhardt P, Meunier PJ, Goemaere S, Lippuner K et al (2007) Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis. Osteoporos Int 18:1211–8

    Article  CAS  PubMed  Google Scholar 

  12. Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwiński E et al (2012) Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res 27:694–701

    Article  CAS  PubMed  Google Scholar 

  13. Orwoll E, Tedlbjaerg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL et al (2012) A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Edocrinol Metab 97:3161–9

    Article  CAS  Google Scholar 

  14. Cummings SR, San MJ, McClung MR, Siris ES, Eastell R, Reid IR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–65

    Article  CAS  PubMed  Google Scholar 

  15. Bone HG, Chapurlat R, Brandi ML, Brown JP, Czerwinski E, Krieg MA et al (2013) The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab 98:4489–92

    Google Scholar 

  16. Al Z (2006) Bisphosphonates are associated with increased risk of jaw surgery in medical claims data: is it osteonecrosis? J Oral Maxillofac Surg 64:917–23

    Article  Google Scholar 

  17. Pazianas M, Blumentals WA, Miller PD (2008) Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int 19:773–9

    Article  CAS  PubMed  Google Scholar 

  18. Grbic JT, Black DM, Lyles KW, Reid DM, Orwoll E, McClung M et al (2010) 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 141:1365–70

    Article  CAS  PubMed  Google Scholar 

  19. Saad F, Brown JE, Van PC, Ibrahim T, Stemmer SM, Stopeck AT et al (2012) 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 23:1341–7

    Article  CAS  PubMed  Google Scholar 

  20. Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA et al (2012) Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combineb analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 48(16):3082–92

    Article  CAS  PubMed  Google Scholar 

  21. Migliorati CA, Epstein JB, Abt E, Berenson JR (2011) Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review. Nat Rev Endocrinol 7:34–42

    Article  CAS  PubMed  Google Scholar 

  22. Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P (2007) A review of the literature on osteonecrosis of the jaw with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 29:1548–58

    Article  CAS  PubMed  Google Scholar 

  23. Hokugo A, Christensen R, Chung EM, Sung EC, Felsenfeld AL, Sayre JW et al (2010) Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats. J Bone Miner Res 30:3–23

    Google Scholar 

  24. Allen MR (2007) Animal models of osteonecrosis of the jaw. J Musculoskelet Neuronal Interact 7:358–60

    CAS  PubMed  Google Scholar 

  25. Allen MR (2009) Bisphosphonates and osteonecrosis of the jaw: moving from the bedside to the bench. Cells Tissues Organs 189:289–94

    Article  CAS  PubMed  Google Scholar 

  26. Katsarelis H, Shah NP, Dhariwal DK, Pazianas M. Infection and medication-related osteonecrosis of the jaw. 2015;1-6

  27. Wimalawansa SJ (2008) Insight into bisphosphonate-associated osteomyelitis of the jaw: pathophysiology, mechanisms and clinical management. Expert Opin Drug Saf 7:491–512

    Article  CAS  PubMed  Google Scholar 

  28. Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M et al (2002) Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rates. Cancer Res 62:6538–44

    CAS  PubMed  Google Scholar 

  29. Santini D, Vincenzi B, Dicuonzo G, Avvisati G, Massacesi C, Battistoni F et al (2003) Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res 9:2893–7

    CAS  PubMed  Google Scholar 

  30. Vincenzi B, Santini D, Dicuonzo G, Battistoni F, Gavasci M, La Cesa A et al (2005) Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients. J Interferon Cytokine Res 25:144–51

    Article  CAS  PubMed  Google Scholar 

  31. Brunello A, Saia G, Bedogni A, Scaglione D, Basso U (2009) Worsening of osteonecrosis of the jaw during treatment with subitinib in a patient with metastatic renal cell carcinoma. Bone 44:173–5

    Article  CAS  PubMed  Google Scholar 

  32. Guarneri V, Miles D, Robert N, Diéras V, Glaspy J, Smith I et al (2010) 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 122:181–8

    Article  CAS  PubMed  Google Scholar 

  33. English BC, Baum CE, Adelberg DE, Sissung TM, Kluetz PG, Dahut WL et al (2010) A SNP in CYP2C8 is not associated with the development of bisphosphonate-related osteonecrosis of the jaw in men with castrate-resistant prostate cancer. Ther Clin Risk Manag 6:579–83

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Sarasquete ME, Garcia-Sanz R, Marin L, Alcoceba M, Chillón MC, Balanzategui A et al (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 112:2709–12

    Article  CAS  PubMed  Google Scholar 

  35. Katz J, Gong Y, Salmasina D, Hou W, Burkley B, Ferreira P et al (2011) Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J Oral Maxillofac Surg 40:605–11

    Article  CAS  PubMed  Google Scholar 

  36. Nicoletti P, Cartsos VM, Palaska PK, Shen Y, Floratos A (2012) Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3. Oncologist 17:279–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hoefert S, Schmitz I, Tannapfel A, Eufinger H (2010) 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 Investig 14:271–84

    Article  PubMed  Google Scholar 

  38. Kunchur R, Goss AN (2008) The oral health status of patients on oral bisphosphonates for osteoporosis. Aust Dent J 53:354–7

    Article  CAS  PubMed  Google Scholar 

  39. Lodi G, Sardella A, Salis A, Demarosi F, Rarozzi M, Carrassi A (2010) Tooth extraction in patients taking intravenous bisphosphonates: a preventive protocol and case series. J Oral Maxillofac Surg 68:107–10

    Article  PubMed  Google Scholar 

  40. Bonacina R, Mariani U, Villa F, Villa A (2011) Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: a review of 282 patients. J Can Dent Assoc 77:b147

    PubMed  Google Scholar 

  41. Hellstein JW, Adler RA, Edwards B et al (2011) 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 142:1243–51

    Article  CAS  PubMed  Google Scholar 

  42. Moretti F, Pelliccioni GA, Montebugnoli L, Marchetti C (2011) A prospective clinical trial for assessing the efficacy of a minimally invasive protocol in patients with bisphosphonate-associated osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112:777–82

    Article  PubMed  Google Scholar 

  43. Ferlito S, Puzzo S, Liardo C (2009) Preventive protocol for tooth extractions in patients treated with zoledronate: a case series. J Oral Maxillofac Surg 69:e1–4

    Article  Google Scholar 

  44. Bashutski JD, Eber RM, Kinney JS et al (2010) Teriparatide and osseous regeneration in the oral cavity. N Engl J Med 363:2396–405

    Article  CAS  PubMed  Google Scholar 

  45. Subramanian G, Cohen HV, Quek SY (2011) A model for the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw and teriparatide's potential role in its resolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112:744–53

    Article  PubMed  Google Scholar 

  46. 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 65:573–80

    Article  PubMed  Google Scholar 

  47. Lau AN, Adachi JD (2009) Resolution of osteonecrosis of the jaw after teriparatide [recombinant human PTH-(1-34)] therapy. J Rjeumatol 36:1835–7

    Article  CAS  Google Scholar 

  48. Cheung A, Seeman E (2010) Teriparatide therapy for alendronate-associated osteonecrosis of the jaw. N Engl J Med 363:2473–4

    Article  CAS  PubMed  Google Scholar 

  49. Lee JJ, Cheng SJ, Jeng JH, Chiang CP, Lau HP, Kok SH (2011) Successful treatment of advanced bisphosphonate-related osteonecrosis of the mandible with adjunctive teriparatide therapy. Head Neck 33:1366–71

    Article  PubMed  Google Scholar 

  50. Narongroeknawin P, Danila MI, Humphreys LG Jr, Barasch A, Curtis JR (2010) Bisphosphonate-associated osteonecrosis of the jaw, with healing after teriparatide: a review of the literature and a case report. Spec Care Dent 30:77–82

    Article  Google Scholar 

  51. Iwamoto J, Yago K, Sato Y, Matsumoto H (2012) Teriparatide therapy for bisphosphonate-associated osteonecrosis of the jaw in an elderly Japanese woman with severe osteoporosis. Clin Drug Investig 32:547–53

    PubMed  Google Scholar 

  52. Wilde F, Heufelder M, Winter K, Hendricks J, Frerich B, Schramm A et al (2011) The role of surgical therapy in the management of intravenous bisphosphonates-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111:153–63

    Article  PubMed  Google Scholar 

  53. Mucke T, Koschinski J, Deppe H, Wagenpfeil S, Pautke C, Mitchell DA et al (2011) Outcome of treatment and parameters influencing recurrence in patients with bisphosphonates-related osteonecrosis of the jaws. J Cancer Res Clin Oncol 137:907–13

    Article  PubMed  Google Scholar 

  54. Ngamphaiboon N, Frustino JL, Kossoff EB, Sullivan MA, O'Connor TL (2011) Osteonecrosis of the jaw: dental outcomes in metastatic breast cancer patients treated with bisphosphonates with/without bevacizumab. Clin Breast Cancer 11:252–7

    Article  CAS  PubMed  Google Scholar 

  55. Vescovi P, Merigo E, Meleti M, Manfredi M, Guidotti R, Nammour S (2012) 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 41:214–21

    Article  CAS  PubMed  Google Scholar 

  56. Matins MA, Martins MD, Lascala CA, Curi MM, Migliorati CA, Tenis CA et al (2012) Association of laser phototherapy with PRP improves healing of bisphosphonate-related osteonecrosis of the jaws in cancer patients: a preliminary study. Oral Oncol 48:79–84

    Article  Google Scholar 

  57. Mozzati M, Gallesio G, Arata V, Pol R, Scoletta M (2012) Platelet-rich therapies in the treatment of intravenous bisphosphonate-related osteonecrosis of the jaw: a report of 32 cases. Oral Oncol 48:469–74

    Article  PubMed  Google Scholar 

  58. Freiberger JJ, Padilla-Burgos R, McGraw T, Suliman HB, Kraft KH, Stolp BW et al (2012) What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: a randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics. J Oral Maxillofac Surg 12:1573–83

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. McMaster University, Hamilton, Canada

    A. Khan & W. Hashem

  2. Dalhousie University, Halifax, Canada

    A. Morrison

  3. University of Toronto, Toronto, Canada

    A. Cheung

  4. Cambridge University, Cambridge, UK

    J. Compston

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  1. A. Khan
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  2. A. Morrison
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  3. A. Cheung
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  4. W. Hashem
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Corresponding author

Correspondence to A. Khan.

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Conflicts of interest

I, Dr. Aliya Khan would like to declare that I am a member of the advisory board with Amgen and Lilly. I have received honorarium from Amgen and Lilly. I am currently participating in a clinical trial with Amgen and Merck; I have recently completed a clinical trial for NPS pharmaceuticals.

I, Dr. Archie Morrison would like to confirm that I have no conflicts of interest.

I, Dr. Angela Cheung would like to declare that I received honoraria and grants (to institution) from Amgen and Eli Lilly.

I, Dr. Juliet Compston would like to confirm that I have no conflicts of interest.

I, Dr. Waleed Hashem would like to confirm that I have no conflicts of interest.

Members of the International Osteonecrosis of the Jaw Task Force

A.A. Khan, Department of Medicine, Divisions of Endocrinology and Metabolism and Geriatrics, McMaster University, Hamilton, ON, Canada

A. Morrison, Division of Oral and Maxillofacial Surgery, Dalhousie University, Halifax, NS, Canada

D.A. Hanley, Departments of Medicine, Community Health Sciences and Oncology, University of Calgary, Calgary, AB, Canada

D. Felsenberg, Centre of Muscle & Bone Research, Charité-University Medicine Berlin, Campus Benjamin Franklin, Free University & Humboldt-University Berlin, Berlin, Germany

L.K. McCauley, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA

F. O’Ryan Kaiser, Permanente Medical Center, Oakland, CA, USA

I.R. Reid, Department of Medicine, University of Auckland, Auckland, New Zealand

S. Ruggiero, New York Center for Orthognathic and Maxillary Surgery, Lake Success, NY, USA

A. Taguchi, Department of Oral and Maxillofacial Radiology, School of Dentistry, Matsumoto Dental University, Shojiri, Japan

S. Tetradis, Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA, USA

N.B. Watts, Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA

M.L. Brandi, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy

E. Peters, University of Alberta, Edmonton, Alberta, Canada

T. Guise, Department of Medicine, Division of Endocrinology at Indiana University, Indianapolis, IN, USA

R. Eastell, Department of Human Metabolism, University of Sheffield, Sheffield, UK

A.M. Cheung, University of Toronto, Toronto, ON, Canada

S.N. Morin, Department of Medicine, McGill University, Montreal, Quebec, Canada

B. Masri, Jordan Osteoporosis Center, Jordan Hospital & Medical Center, Amman, Jordan

C. Cooper, MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; NIHR Nutrition Biomedical Research Centre, University of Southampton, Southampton, UK; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK

S. Morgan, University of Alabama at Birmingham Osteoporosis Prevention and Treatment Clinic, Division of Clinical Immunology and Rheumatology, Birmingham, AL, USA

B. Obermayer-Pietsch, Medical University Graz, Div. Endocrinology and Metabolism, Department of Internal Medicine, Graz, Austria

B.L. Langdahl, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

R. Al Dabagh, Faculty of Dentistry , University of Toronto, Toronto, Canada

K.S. Davison, Department of Graduate Studies, University of Victoria, Victoria, BC, Canada

D. Kendler, Department of Medicine, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada

G.K. Sándor, Department of Oral and Maxillofacial Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland

R.G. Josse, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada

M. Bhandari, Division of Orthopaedic Surgery, Department of Surgery and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada

M. El Rabbany, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada

D.D. Pierroz, International Osteoporosis Foundation (IOF), Nyon, Switzerland

R. Sulimani, College of Medicine, King Saud University, Riyadh, Saudi Arabia

D.P. Saunders, Department of Dental Oncology, Northeast Cancer Centre/Health Science North, Sudbury, ON, Canada

J.P. Brown, Laval University, Quebec, Quebec, Canada

J. Compston, Cambridge Biomedical Campus, Cambridge, UK

R. Rizzoli, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland

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This article was written on behalf of the International Osteonecrosis of the Jaw Task Force. A full list of the members of this body can be found at the end of the article.

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Khan, A., Morrison, A., Cheung, A. et al. Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015. Osteoporos Int 27, 853–859 (2016). https://doi.org/10.1007/s00198-015-3335-3

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