Purpose: Details regarding risk factors, onset, and outcomes for denosumab-related osteonecrosis (DRONJ) are sparse. This study examines the clinical characteristics and operative and non-operative therapeutic outcomes in patients with DRONJ not previously exposed to other antiresorptives. Methods: A retrospective medical record review was conducted, and data were collected, including clinical findings, management, healing outcomes, and radiologic, histologic, and micro-computed tomography (CT) analyses. Results: Seventeen patients were treated with denosumab, with 14.1 +/- 8.3 doses before DRONJ onset. The majority of lesions were observed at sites of dental prostheses (41%) and dental extractions (35%). Sixteen patients were managed non-operatively (10/16) or operatively (6/16) with either major (5/6) or minor surgery (1/6) and included in the follow-up analysis. Complete healing was significant in patients treated with major surgery (80%) compared to the non-operative group (20%; p < 0.035). Denosumab was discontinued in 60% of non-operative patients and major surgery patients with no effect on healing. Histologic findings of 4 patients analyzed exhibited a decreased number of osteocyte lacunae, and micro CT of 3 patients scanned revealed trabecular thickening. Conclusion: DRONJ lesions occurred mostly at sites of prostheses sores after a mean of 14 doses of denosumab. Major surgery demonstrated more complete healing than non-operative management, and denosumab cessation did not improve healing outcomes. (C) 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.