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

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Dental School, National and Kapodistrian University of Athens, Bouboulinas 41, N. Psyhico, 154 51, Athens, Greece

    Ourania Nicolatou-Galitis, Maria Kouri, Erofili Papadopoulou, Emmanouil Vardas & Dimitra Galiti

  2. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Health System, Los Angeles CA and City of Hope National Medical Center, Duarte, CA, USA

    Joel B. Epstein

  3. Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA

    Sharon Elad

  4. Sector of Oral Medicine “V. Margiotta”, Department Di.Chir.On.S, University of Palermo, Palermo, Italy

    Giuseppina Campisi

  5. Consultant Medical Oncologist, Oncology Department, Veterans Hospital (NIMTS), Athens, Greece

    Nikolaos Tsoukalas

  6. Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Istanbul University, Istanbul, Turkey

    Kivanc Bektas-Kayhan

  7. Hematology/Oncology, Mayo Clinic Florida, Jacksonville, FL, USA

    Winston Tan

  8. CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium

    Jean-Jacques Body

  9. Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA

    Cesar Migliorati

  10. Section of Oral Medicine, University of Connecticut School of Dental Medicine, Farmington, CT, USA

    Rajesh V. Lalla

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  1. Ourania Nicolatou-Galitis
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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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Nicolatou-Galitis, O., Kouri, M., Papadopoulou, E. et al. Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review. Support Care Cancer 27, 383–394 (2019). https://doi.org/10.1007/s00520-018-4501-x

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