Risk factors for osteonecrosis of the jaw in oral cancer patients after surgery and eventual adjuvant treatment: The potential role of chemotherapy

Abstract

Background and purpose: To identify the risk factors for osteonecrosis of the jaw (ONJ) in oral cancer patients after surgery with and without adjuvant therapy in a nationwide, population-based study.

Material and methods: Using the Taiwan National Health Insurance Research Dataset, we recruited patients with newly diagnosed oral cancer between 1997 and 2011. All of them underwent primary surgery. Data regarding demographic characteristics; tooth extractions; medications; and cancer treatments, including types of mandibular surgery, radiotherapy and platinum-based chemotherapy, were collected for analysis.

Results: We identified 25,858 patients who suffered 2802 ONJ events. The ONJ incidence rate was 3.45 per 100 person-years. Lip cancer was associated with the highest risk of ONJ, followed by buccal mucosa, gum, mouth floor and tongue cancer. Using a time-dependent Cox regression model, multivariable analysis demonstrated that mandibulotomy (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.01-1.55; p<0.001), radiotherapy (HR, 1.39; 95% CI, 1.26-1.54; p<0.001) and platinum-based chemotherapy (HR, 1.94; 95% CI, 1.56-2.41; p<0.001) were significant risk factors for ONJ. In the subgroup analysis of patients receiving radiotherapy and patients not receiving radiotherapy, platinum-based chemotherapy remained a risk factor for ONJ.

Conclusions: Mandibulotomy, radiotherapy and platinum-based chemotherapy were associated with an increased ONJ risk. Chemotherapy was a risk factor regardless of whether radiotherapy was administered.

Keywords: Chemotherapy; Oral cancer; Osteonecrosis of the jaw; Radiotherapy; Risk factor.