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

Hiroaki Ikesue,Hisateru Yasui,Keisuke Tomii,Nobuyuki Muroi,Toshihiko Takenobu,Moe Mouri,Tohru Hashida,Takayuki Ishikawa,Mai Ikemura,Masaki Hirabatake,Hideaki Tomita,Hironori Katoh,Mutsushi Kawakita,Shinsuke Yamamoto

doi:10.1007/s00520-021-06018-x

Abstract

PurposeThis 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.MethodsThe 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.ResultsAmong 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).ConclusionThe 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.

Highlights

Bone metastases are common in advanced cancer, resulting in clinically important complications such as cancer-related pain, fractures, spinal cord compression, and hypercalcemia [1]
Between January 2012 and September 2016, 580 adult patients with bone metastases due to cancer were treated with denosumab or zoledronic acid
The incidence of medication-related osteonecrosis of the jaw (MRONJ) was significantly higher in the denosumab group than in the zoledronic acid group (12.6 vs 4.4%, P = 0.006)

Summary

Introduction

Bone metastases are common in advanced cancer, resulting in clinically important complications such as cancer-related pain, fractures, spinal cord compression, and hypercalcemia [1]. The results of randomized controlled trials comparing denosumab and zoledronic acid for the prevention of SREs in metastatic bone diseases have shown that denosumab is superior in cases of breast [12] and prostate cancer [13] and noninferior in cases of solid tumors and multiple myeloma [14, 15]. Both zoledronic acid and denosumab are widely used for the treatment of bone metastases

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