Contribution of Antiangiogenic Agents to the Risk of Medication-related Osteonecrosis of the Jaw in Combination with Antiresorptive Agents

Abstract

A BSTRACT Aim: The aim of this preliminary study was to evaluate in an oncological population the association risk of antiangiogenic (AA) agents to antiresorptive (AR) agents on the incidence and the severity of medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: In this prospective study, we reviewed the medical records and clinical variables of 59 consecutive oncologic patients who developed MRONJ. For all patients, we retrieved the following variables: age, gender, alcohol and tobacco use, type of cancer, use of corticosteroids for >3 months, history of diabetes, MRONJ staging, combination of AR and AA agents, dental history (surgery, prosthesis) or spontaneous, site of MRONJ, delay between AR and AA first intake, and MRONJ development. Patients were divided into two groups according to drugs therapy they underwent: group 1 (G1) including patients treated with AR agents alone and group 2 (G2) including patients receiving antiresorptive–antiangiogenic drugs (AR+AA). The degree and the therapeutical success were defined as primary outcomes and the number, the localization, and the delay in onset of the lesions as secondary outcomes. In order to identify predictive factors of osteonecrosis-free interval time, univariate and multivariate Cox regression was performed. Statistical tests were carried out using the IBM ® SPSS ® Statistics software. All reported P -values are two-tailed and were considered to be significant when less than 0.05. Results: Among the 47 patients who received AR agent alone (group 1), the mean treatment duration before diagnosis of MRONJ was 39.2 months. In the second group ( n = 12), patients developed MRONJ with a comparable mean time of 55 months ( P = 0.16). According to the staging of MRONJ at the time of diagnosis, no significant difference ( P = 0.736) was observed between the two groups. Moreover, the treatment applied was not statistically different in both the groups and was successful in 36.17% of the patients in group 1 and 58.33% of the patients in group 2. No statistically difference was reported in both the groups ( P = 0.16). After statistical analysis, no significant difference in terms of MRONJ localization ( P = 0.13) was observed. Finally, the incidence of spontaneous MRONJ was comparable in both the groups. Statistical analysis revealed that total time of treatment was the only factor associated with poor osteonecrosis-free interval time (hazard ratio 0.99; P = 0.001). Interestingly, the combination of an AA and AR agent was not a significant predictor factor of the interval time before the diagnosis of osteonecrosis. Additionally, corticosteroid use, diabetes mellitus, and dental consultation before treatme...

Clinical Performance of Implant-Supported Prostheses in the Rehabilitation of Patients Previously Treated for Medication-Related Osteonecrosis of the Jaws (MRONJ): A Systematic Review

“…Research has elucidated the complex interplay of factors contributing to MRONJ, including their influence on bone homeostasis, leading to compromised bone healing and increased susceptibility to necrosis and infection [ 12 ]. Among a long list of hypotheses [ 12 , 24 ], impaired angiogenesis is considered to play a pivotal role in the development of MRONJ by blocking angiogenesis via inhibition of cell proliferation [ 25 , 26 ]. Supporting this idea, reduced circulating growth factors have been measured in patients under bisphosphonate therapy [ 27 , 28 ].…”