Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

Abstract

Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

Risk Evaluation of Denosumab And Zoledronic Acid For Medication-Related Osteonecrosis of The Jaw In Patients With Bone Metastases: A Propensity Score-Matched Analysis

“…Moreover, this result was also clearly con rmed by propensity score-matched analysis. The higher risk for developing MRONJ with denosumab than with ZA was consistent with some previous real-world data [40][41][42][43]. Previous randomized controlled trials reported that the incidence of MRONJ in patients treated with denosumab was not signi cantly different from that in patients treated with ZA, although it tended to be higher in the former [25, 27, 32-34, 36, 37].…”

“…The incidences of MRONJ in the present study were 9.6% and 4.8% in the denosumab and ZA groups, respectively. The reported incidence of MRONJ is 1-17% [25,27,[29][30][31][32][33][34][35][36][37][38][39][40][41][42], and the incidences of MRONJ in our study were within this range for both groups.…”

“…The higher incidence of denosumab-associated osteonecrosis of the jaw seems to re ect its superior effect on bone resorption compared to that of ZA [26,32,33]. Recently, we reported that MRONJ caused by denosumab resolves faster than that caused by ZA [40]. We believe that diagnosing MRONJ at an earlier stage through appropriate monitoring and multidisciplinary collaborative work with healthcare providers is essential for BMA treatment [44].…”

“…Another randomized control trial also reported that the incidences of MRONJ were low in patients with multiple myeloma receiving both denosumab (4.1%; n = 35/850) and ZA (2.8%; n = 24/852) [37]. In contrast, in retrospective observational studies, the reported incidences of MRONJ were found to vary from 2-17% [29][30][31][38][39][40][41][42] and were relatively higher than those in randomized controlled trials. In randomized controlled trials, the study protocol speci ed that all participants underwent scheduled periodic dental examinations (e.g., at baseline and every 6 months thereafter) [25, 27, 32-34, 36, 37].…”

Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients

“…Studies have shown that invasive dental procedures such as tooth extraction are a risk factor for the onset of MRONJ 4 – 7 , and therefore, tooth extraction tends to be avoided in these patients. The 2014 American Association of Oral and Maxillofacial Surgeons (AAOMS) position paper on medication-related osteonecrosis of the jaw update described that dentoalveolar surgeries such as tooth extraction are considered a major risk factor for developing MRONJ 1 .…”