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Supportive Care in Cancer

, Volume 27, Issue 2, pp 383–394 | Cite as

Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review

  • Ourania Nicolatou-Galitis
  • Maria Kouri
  • Erofili Papadopoulou
  • Emmanouil Vardas
  • Dimitra Galiti
  • Joel B. Epstein
  • Sharon Elad
  • Giuseppina Campisi
  • Nikolaos Tsoukalas
  • Kivanc Bektas-Kayhan
  • Winston Tan
  • Jean-Jacques Body
  • Cesar Migliorati
  • Rajesh V. Lalla
  • for the MASCC Bone Study Group
Review Article

Abstract

Introduction

The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing.

Objective

To review characteristics of ONJ in cancer patients receiving non-antiresorptives.

Methods

A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO.

Results

Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted.

Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications.

Conclusions

Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors.

Keywords

Bone resorption Cytotoxic chemotherapy Immune checkpoint inhibitors Inhibitors of angiogenesis mTOR inhibitors Tyrosine kinase inhibitors BRAF inhibitors Osteonecrosis of the jaw 

Notes

Acknowledgements

We thank the MASCC Board for the opportunity to work on this project, within the Bone Study Group.

Compliance with ethical standards

Conflict of interest

Ourania Nicolatou-Galitis and Cesar Migliorati have received consultant fee from AMGEN. Maria Kouri, Erofili Papadopoulou, Emmanouil Vardas, Dimitra Galiti, Joel Epstein, Sharon Elad, Giuseppina Campisi, Nikolaos Tsoukalas, Kivanc Bektas-Kayhan, Winston Tan, Jean-Jacques Body, and Rajesh Lalla declare no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ourania Nicolatou-Galitis
    • 1
  • Maria Kouri
    • 1
  • Erofili Papadopoulou
    • 1
  • Emmanouil Vardas
    • 1
  • Dimitra Galiti
    • 1
  • Joel B. Epstein
    • 2
  • Sharon Elad
    • 3
  • Giuseppina Campisi
    • 4
  • Nikolaos Tsoukalas
    • 5
  • Kivanc Bektas-Kayhan
    • 6
  • Winston Tan
    • 7
  • Jean-Jacques Body
    • 8
  • Cesar Migliorati
    • 9
  • Rajesh V. Lalla
    • 10
  • for the MASCC Bone Study Group
  1. 1.Dental SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Health System, Los Angeles CA and City of Hope National Medical CenterDuarteUSA
  3. 3.Eastman Institute for Oral HealthUniversity of Rochester Medical CenterRochesterUSA
  4. 4.Sector of Oral Medicine “V. Margiotta”, Department Di.Chir.On.SUniversity of PalermoPalermoItaly
  5. 5.Consultant Medical Oncologist, Oncology DepartmentVeterans Hospital (NIMTS)AthensGreece
  6. 6.Faculty of Dentistry, Department of Oral and Maxillofacial SurgeryIstanbul UniversityIstanbulTurkey
  7. 7.Hematology/Oncology, Mayo Clinic FloridaJacksonvilleUSA
  8. 8.CHU BrugmannUniversité Libre de BruxellesBrusselsBelgium
  9. 9.Department of Oral and Maxillofacial Diagnostic SciencesUniversity of Florida College of DentistryGainesvilleUSA
  10. 10.Section of Oral MedicineUniversity of Connecticut School of Dental MedicineFarmingtonUSA

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