Combined Administration of Bisphosphonates, Chemotherapeutic Agents, and/or Targeted Drugs Increases the Risk for Stage 3 Medication-Related Osteonecrosis of the Jaw: A 4-Year Retrospective Study

Abstract

Objectives. Patients with stage 3 medication-related osteonecrosis of the jaw (MRONJ) suffer from severe complications. Chemotherapeutic agents and targeted drugs are considered to be associated with the development of MRONJ. However, little is known regarding the association of those agents with stage 3 MRONJ. The purpose of this study is to analyze the comprehensive medication history of patients with advanced-stage MRONJ (stage 2 and stage 3) and evaluate the possible risk factors for stage 3 MRONJ. Patients and Methods. Sixty patients with advanced-stage MRONJ were involved in this retrospective study. Patients with developmental maxillofacial anomalies, previous radiation in the head and neck areas, and jaw bone tumors were excluded from the study. All patients were divided into two groups by their MRONJ stage (stage 2 or stage 3). Demographic and clinical characteristics, comprehensive medication data (bisphosphonates, chemotherapeutic agents, targeted drugs, and immunosuppressive agents), and results of serological biomarkers were recorded and compared between two groups. Univariate and multivariate logistic regressions were performed by SPSS 25.0 for evaluating risk factors of stage 3 MRONJ. Results. Our results indicate that chemotherapy ( adjusted OR = 3.43 ; 95% CI: 1.03 to 11.38), targeted drugs ( adjusted OR = 3.69 ; 95% CI: 1.06 to 12.80), and maxillary lesions ( adjusted OR = 4.26 ; 95% CI: 1.19 to 15.23) increase the risk of stage 3 MRONJ. Conclusion. The outcome of this study justifies that chemotherapeutic agents and targeted drugs are probably risk factors for stage 3 MRONJ. In addition, the osteonecrosis in maxilla is more easily to develop into stage 3 MRONJ. Intense clinical observation is recommended in MRONJ patients with maxillary osteonecrosis and in those who concurrently administered bisphosphonates, chemotherapeutic agents, and/or targeted drugs. This trial is registered with ChiCTR2000032428.

CD34 and CD105 Microvessels in Resected Bone Specimen May Implicate Wound Healing in MRONJ

“…Patients attributable to the three stages of the disease were treated, with a higher frequency of cases attributable to stage II. It has been reported that early stage treated with radical surgery showed a better treatment outcome [50]. Nevertheless, the MRONJ stage did not play a significant role in the incidence of surgical failure (p = 0.2352), in this case series.…”

Cancer Patients at Risk for Medication-Related Osteonecrosis of the Jaw. A Case and Control Study Analyzing Predictors of MRONJ Onset

“…In addition to well-known medications, MRONJ may be a major adverse reaction to several new-generation anticancer drugs due to unknown mechanisms [ 57 , 58 ]. To date, several medications have been somehow implicated in MRONJ on the basis of experience gained through isolated data, case series reports, and literature reviews [ 16 , 17 , 18 , 59 , 60 ]. Recent reports have suggested a relatively high MRONJ risk in patients with a combined administration of bisphosphonates and targeted drugs [ 30 , 49 ].…”

“…Recent reports have suggested a relatively high MRONJ risk in patients with a combined administration of bisphosphonates and targeted drugs [ 30 , 49 ]. It is known, for example, that the combination of anti-VEGFR and bone antiresorptive agents may increase the risk of MRONJ [ 60 , 61 , 62 ]. Similarly, it was well confirmed that mTOR inhibitors have a strong immunosuppressive effect, which can lead to delayed healing of oral soft tissues and persistent infections favoring the onset of the osteonecrotic process [ 63 , 64 ].…”

“…Furthermore, dental interventions may also be required during the course of bone resorptive therapy [ 79 ]. Thus, for those who have had a concurrent administration of bisphosphonates and new anti-cancer molecules, dentists should be aware of a potentially increasing risk of severe MRONJ [ 60 ]. It is the authors’ opinion that risk assessment of cancer patients about to initiate bone targeting agents should be the expression of a strategic alliance between the oral surgeon and the oncologist, by introducing information such as overall survival and performance status in a combined evaluation.…”

Review of Myeloma Therapies and Their Potential for Oral and Maxillofacial Side Effects

“…However, exposure to these drugs is a major risk factor for the development of MRONJ. Recent data suggest that combination therapies might also increase the risk of developing MRONJ and cause more advanced necrosis especially in the maxilla; however, this study was not limited to patients with myeloma [22]. Another study of 459 MRONJ cases reported that out of 52 patients undergoing treatment with BMA, 11 had also received lenalidomide, 12 received thalidomide, 11 received bevacizumab, 9 received everolimus, and 9 received sunitinib as part of the drug therapy [2].…”