Abstract

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an adverse event induced by antiresorptive agents (ARAs). The purpose of this study was to evaluate variables, mainly surgery and hyperbaric oxygen (HBO) therapy, associated with treatment outcomes in patients with a diagnosis of ARONJ at a single center. We enrolled consecutive patients who presented to our hospital for the management of stage 2 or 3 ARONJ between January 2003 and December 2019. The relationship between potentially predictive factors and outcome variables was examined using statistical analyses, along with a subgroup analysis based on disease stage. Of 252 patients included in this study, 206 had stage 2 ARONJ and 46 had stage 3 ARONJ. There were 119 patients with osteoporosis and 133 with malignant disease. In total, 139 patients were healed, and the healing rate of patients with stage 3 ARONJ was lower than that of patients with stage 2 ARONJ. With regard to the combination of surgery and HBO therapy, most patients underwent HBO before and after surgery. In the univariable analysis, surgery showed a therapeutic effect in both stage 2 and 3 ARONJ, whereas HBO showed a therapeutic effect in stage 2 ARONJ. In the multivariable analysis for stage 2 ARONJ, extensive surgery showed a stronger association with healing than conservative surgery, whereas ≥46 sessions of HBO therapy was less associated with healing than was non-HBO therapy. Our findings suggest that extensive surgery is highly effective against ARONJ regardless of disease stage if there is a sequestrum separation and systemic tolerance, whereas HBO therapy before and after surgical approach can be effective. Further studies are needed to identify treatment strategies for patients with treatment-refractory ARONJ who may be forced to undergo long-term HBO therapy with the expectation of sequestrum separation.

Highlights

  • Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an adverse event that is induced by antiresorptive agents (ARAs), such as bisphosphonate (BP) and denosumab (Dmab), as well as angiogenesis inhibitors

  • In this single-center cohort study, we evaluated the association of surgical and hyperbaric oxygen (HBO) treatments with clinical outcomes in patients with ARONJ, along with a subgroup analysis based on the disease stage; this included the type of surgery and the timing and number of HBO therapy sessions, which are important clinical considerations

  • In the multivariable analysis for stage 2 ARONJ, extensive surgery displayed a stronger association with healing than conservative surgery, while 46 sessions of HBO therapy was less associated with healing than non-HBO therapy

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Summary

Introduction

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an adverse event that is induced by antiresorptive agents (ARAs), such as bisphosphonate (BP) and denosumab (Dmab), as well as angiogenesis inhibitors. Later in 2011, cases of Dmab-related osteonecrosis of the jaw (DRONJ) were reported during randomized clinical trials [2]. Clinical and basic research regarding ARONJ have been performed to clarify its pathophysiological mechanisms, the reasons why this condition occurs in patients taking ARAs remain unknown [3]. The best treatment practices for the management of patients with ARONJ are controversial since the pathophysiological mechanisms are unclear. Several clinical studies have reported that a surgical approach is more successful than a nonsurgical approach for the treatment of ARONJ [4,5,6,7,8,9]

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