Risk evaluation of denosumab and zoledronic acid for medication-related osteonecrosis of the jaw in patients with bone metastases: a propensity score\u2013matched analysis

Hiroaki Ikesue,Shinsuke Yamamoto,Masaki Hirabatake,Nobuyuki Muroi,Mayu Morimoto,Kohei Doi,Tohru Hashida,Toshihiko Takenobu

doi:10.1007/s00520-021-06634-7

Hiroaki Ikesue, Shinsuke Yamamoto + Show 6 more

Open Access

https://doi.org/10.1007/s00520-021-06634-7

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Abstract

PurposeThis study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis.MethodsThe medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups.ResultsAmong the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65–5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38–7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score–matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17–5.01; p = 0.016).ConclusionThe results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

Highlights

Bone metastasis is commonly found in patients with advanced cancers; it leads to clinically important complications, such as pain, hypercalcemia, spinal cord compression, and fractures [1, 2]
Despite the usefulness of bone-modifying agents (BMAs), significant safety concerns including hypocalcemia [15] and medication-related osteonecrosis of the jaw (MRONJ) have been reported as severe side effects associated with their use [16]
The cumulative incidences of MRONJ in the denosumab group were significantly higher than those in the zoledronic acid (ZA) group in both cohorts (p = 0.002, Fig. 2a) and in the propensity score–matched cohort (p = 0.017, Fig. 2b). This is the first study showing that denosumab treatment can significantly increase the risk of developing MRONJ, when compared to ZA, among patients who received BMA treatment for bone metastasis in a real-world clinical practice setting using a propensity score–matched analysis

Summary

Introduction

Bone metastasis is commonly found in patients with advanced cancers; it leads to clinically important complications, such as pain, hypercalcemia, spinal cord compression, and fractures [1, 2]. Denosumab is a fully humanized monoclonal antibody against nuclear factor-kappa B (NFκB) ligand (RANKL) [14]. Both ZA and denosumab demonstrated efficacy in preventing skeletal complications in patients with bone metastasis secondary to solid tumors or osteolytic lesions of multiple myeloma. Despite the usefulness of bone-modifying agents (BMAs), significant safety concerns including hypocalcemia [15] and medication-related osteonecrosis of the jaw (MRONJ) have been reported as severe side effects associated with their use [16].

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