What Affects Healing Rates in Patients Treated for Medication-Related Osteonecrosis of the Jaw? The Role of Operative Therapy and Other Clinical Factors

Abstract

Background

In the therapy of medication-related osteonecrosis of the jaw (MRONJ), the healing rate, effectiveness of operative therapy, and factors associated with healing remain unclear.

Purpose

This study aimed to estimate MRONJ therapy healing rates and identify associated prognostic factors.

Study Design, Setting, Sample

A 25-center prospective cohort study was conducted on 291 patients with MRONJ treated with a common therapeutic protocol during 2013–2016. Patients unable to continue examinations or treatment were excluded.

Predictor Variable

The primary predictor variable was MRONJ therapy grouped into two categories: operative and nonoperative. Secondarily, the prognostic factors categorized as demographic, medical, clinical, and perioperative were evaluated.

Main Outcome Variables

The primary outcome variable was treatment duration, defined as the time (in months) between the initiation of therapy and when the site was healed or the date of the final visit or loss to follow-up.

Covariates

Not applicable.

Analyses

Descriptive statistics and 3-year cumulative healing rates were calculated. The association between clinical factors and time to healing was analyzed using bivariate and multivariate analyses and propensity score analysis. P < .05 was considered significant.

Results

We analyzed data from 291 subjects with 76 (26.1%) and 215 (73.9%) subjects in the operative and nonoperative therapy groups, respectively. The healing rates for operative and nonoperative therapies were 95.8 and 70.7%, respectively (hazard ratio [HR] = 1.6, 95% confidence interval [CI] = 1.1–2.2, P value [P] < .01). The healing rates in patients for whom anti-resorptive agent (ARA) treatment was discontinued and continued were 87.2 and 37.4%, respectively (HR = 1.8, 95% CI = 1.1–3.0, P = .02). In a multiple regression analysis using ARA indication, the therapy method showed a significant association in the MRONJ malignancy group (HR = 2.75, 95% CI = 1.46–5.17, P < .01).

Conclusion and Relevance

Operative therapy and ARA discontinuation were associated with better healing rates in MRONJ therapy. However, the choice of therapy for MRONJ should be based on a comprehensive consideration of the patient's condition. ARA discontinuation should be considered an adjunctive measure because of the possibility of adverse events such as fragility fractures and skeletal related events.