Osteonecrosis of the jaws associated with protein kinase inhibitors: a systematic review

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Abstract
This systematic review analysed evidence relating to medication-related osteonecrosis of the jaws (MRONJ) associated with protein kinase inhibitors in antiresorptive naïve patients. A literature search of major biomedical databases was conducted in March 2020. Information extracted from relevant articles included bibliographic information, patient characteristics, MRONJ characteristics at diagnosis, management strategies and outcomes. Sixteen studies, representing data from 17 patients, were included for final analysis. Descriptive statistics were used to synthesis available data. Eleven protein kinase inhibitors were implicated, with a mean exposure of 13 months prior to MRONJ. Renal cell carcinoma was the primary diagnosis in 41.2% of patients. Patient symptoms, clinical features, radiographic findings and histological findings were consistent with those previously described in patients with MRONJ associated with antiresorptive medications. Overall, there was a 75% rate of cure, with a mean healing time of 17.2 weeks. Patients were treated surgically in 53.3% of the cases. Patients treated surgically achieved complete healing in 100% of cases, compared with 58% in those treated conservatively. Drug discontinuation was reported in 69.2% of patients. Patients who had the offending drug discontinued achieved complete healing in 75% of cases, compared with 50% in those who did not. Evidence relating to MRONJ associated with protein kinase inhibitors is of low quality. From the available data, there are notable differences relating to patient characteristics, treatment strategies and outcomes, between MRONJ associated with protein kinase inhibitors compared with antiresorptives. Higher quality evidence is required to support the findings of this review.

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