Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review.
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.
['Nicolatou-Galitis|Ourania|O|', 'Kouri|Maria|M|', 'Papadopoulou|Erofili|E|', 'Vardas|Emmanouil|E|', 'Galiti|Dimitra|D|', 'Epstein|Joel B|JB|', 'Elad|Sharon|S|', 'Campisi|Giuseppina|G|', 'Tsoukalas|Nikolaos|N|', 'Bektas-Kayhan|Kivanc|K|', 'Tan|Winston|W|', 'Body|Jean-Jacques|JJ|', 'Migliorati|Cesar|C|', 'Lalla|Rajesh V|RV|', '|||']
D000328:Adult D000368:Aged D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw D050071:Bone Density Conservation Agents D004164:Diphosphonates D005260:Female D006801:Humans D007568:Jaw D008297:Male D008875:Middle Aged D010020:Osteonecrosis
Osteonecrosis of the jaw Tyrosine kinase inhibitors Immune checkpoint inhibitors Cytotoxic chemotherapy BRAF inhibitors Bone resorption Inhibitors of angiogenesis mTOR inhibitors