Medication-Related Osteonecrosis of the Jaw in Patients Treated Concurrently with Antiresorptive and Antiangiogenic Agents: Systematic Review and Meta-Analysis

Abstract

Introduction Medication-related osteonecrosis of the jaws (MRONJ) is a known adverse event related to the use of antiresorptive (AR) drugs. More recently, an association between antiangiogenic (AA) drugs and MRONJ has been suggested. This review aimed to investigate the overall prevalence and relative risk of MRONJ in patients treated concurrently with AA and AR agents in comparison with a single AA or AR drug. Methods A review protocol was registered with PROSPERO (ID: CRD42020214244). A systematic literature search, study selection, quality assessment, and data extraction were carried out following PRISMA guidelines. Random-effects meta-analysis models were used to summarize relative estimates for the outcomes, namely prevalence and relative risk of MRONJ. Exposure variable included type of drug, specifically AA and AR agents administered either concurrently or individually. Results Eleven studies were included in the final qualitative and quantitative syntheses. The overall pooled weighted prevalence of MRONJ with concurrent AA-AR drugs was 6% (95% CI: 3–8%), compared with 0% (95% CI: 0–0%) for AA only and 5% (95% CI: 0–10%) for AR only. However, high heterogeneity was noted among included studies. Retrospective cohort studies showed a higher pooled prevalence of 13% (95% CI: 10–17%) for concurrent AA-AR therapy. The pooled risk ratio for MRONJ revealed a risk with concurrent AA-AR drugs 2.57 times as high as with AR only (95% CI: 0.84–7.87); however, this difference was not statistically significant. Concurrent AA-AR drugs had a risk for MRONJ 23.74 times as high as with AA only (95% CI: 3.71–151.92). Conclusions High-quality, representative studies are needed for accurate estimation of relative risk of MRONJ with concurrent AA and AR therapy.

Medication-related osteonecrosis: Literature review

“…With respect to risk factors, Zheng J et al and Otto S et al mention that part of the success of prevention is a correct anamnesis, since patients who are going to receive medications associated with the development of osteonecrosis should not present oral infectious processes and their oral health must be optimal. Evidence shows that dental care prior to starting treatment with bisphosphonates prevents the development of MRONJ (31) (32); information corroborated by Srivastava A et al, who emphasize that the treatment of dental caries, periodontal disease, and extraction of teeth infected or at risk of developing infection must be carried out at least 4 weeks before therapy with antiangiogenic and antiresorptive drugs (24) (34).…”

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“…While underutilization of BMAs can lead to serious SREs, overutilization has the potential for unnecessary adverse events (hypocalcemia, ONJ, atypical fractures, etc.) and financial toxicities [ 43 , 44 , 45 , 46 ]. Pre-implementation chart review in our study also showed inappropriate usage of BMAs in 41.5% of cases.…”

Craniofacial disorders and dysplasias: Molecular, clinical, and management perspectives

“…Third, there should be no history of radiation therapy ( Ruggiero et al, 2022 ). Recently, an association between antiangiogenic medication and MRONJ has been suggested ( Srivastava et al, 2021 ). Although Raloxifene, a selective estrogen receptor modulator has fewer side effects relative to other antiresorptives, MRONJ has also been reported in some patients on Raloxifene ( Bindakhil et al, 2021 ).…”