Medication-related osteonecrosis of the jaws (MRONJ) in cancer patients treated with denosumab VS. zoledronic acid: A systematic review and meta-analysis

A Limones, L-M Sáez-Alcaide, S-A Díaz-Parreño, A Helm, M-M Bornstein, P Molinero-Mourelle, A Limones, L-M Sáez-Alcaide, S-A Díaz-Parreño, A Helm, M-M Bornstein, P Molinero-Mourelle

Abstract

Background: The aim of the present study was to analyse the incidence, risk ratio (RR) and prognoses of two types of medication-related osteonecrosis of the jaws (MRONJ): denosumab-related osteonecrosis of the jaws (DRONJ) and Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) in cancer patients under treatment with denosumab or zoledronic acid (ZA).

Material and methods: An electronic and manual search was conducted for randomized controlled trials (RCTs) until May 2019. Assessment of the identified studies, risk of bias and data extraction were performed independently by two reviewers. The incidence of DRONJ and BRONJ and the RR to develop MRONJ were calculated at 1 year, 2 years and 3 years of exposure. It was also calculated the odds ratio (OR) of their respective prognoses. They were calculated normalizing the values of the individual studies to 1 year, 2 years or 3 years when necessary through robust regression models using a statistical program.

Results: From 1.277 references identified, 8 RCTs were included, which comprised a total of 13.857 patients with a variety of neoplasms. The incidence of DRONJ in cancer patients under treatment with denosumab ranged from 0.5 to 2.1% after 1 year, 1.1 to 3.0% after 2 years, and 1.3 to 3.2% after 3 years of exposure. The incidence of BRONJ in cancer patients under treatment with ZA ranged from 0.4 to 1.6% after 1 year of exposure, 0.8 to 2.1% after 2 years, and 1.0 to 2.3% after 3 years of exposure. Statistically significant differences were found between denosumab and ZA in the risk of developing MRONJ after 1, 2 and 3 years of exposure. Nevertheless, there were no significant differences in terms of patient prognosis.

Conclusions: Denosumab is associated with a significantly higher risk of developing MRONJ compared to ZA. Nevertheless, no differences were found in its prognoses.

Conflict of interest statement

Conflicts of interest The authors received no financial support and declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1
Figure 1
PRISMA flow chart for the present systematic review and meta-analysis.
Figure 2
Figure 2
Assessment of the risk of bias. A) The summary of the Cochrane Collaboration’s tool for assessing risk of bias for the included studies. B) Evaluation of publication bias through Funnel plot.
Figure 3
Figure 3
The summary of the normalized values of the individual studies and diagram of the course of MRONJ during the first 3 years.

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