A multicenter observational study on Medication-Related Osteonecrosis of the Jaw (MRONJ) in advanced cancer and myeloma patients of a cancer network in North-Western Italy

Abstract

Background Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) related to cancer and myeloma treatments is undetermined, with scarce data varying from 2 to 7.8/million/year in limited investigated populations. A 9-years [2009-2018] regional-wide survey was conducted, deploying the North-Western Italy Cancer Network (“Rete Oncologica Piemonte e Valle d’Aosta”), to assess number and main characteristics of MRONJ cases among myeloma/cancer patients, within a population of 4.5 million inhabitants. Material and Methods MRONJ cases were collected retrospectively from January 2009 to June 2015; from July 2015 to December 2018, data were collected prospectively. Number of new MRONJ cases per year, underlying disorder, drug(s) administered, treatment duration, site and onset timing of MRONJ were detailed. Results 459 MRONJ cases were identified. Primary diseases were breast cancer (46%), prostate cancer (21%), myeloma (19%), and other types of carcinoma (14%). Patients received antiresorptive treatment either alone (399; 88.47%) or in combination with biological agents (52; 11.53%); 8 patients (1.7%) received only antiangiogenic drugs. Zoledronic acid [388] and denosumab [59] were the most frequently administered drugs. Mandible was involved in 296 (64,5%) cases. Number of new MRONJ cases was stable from 2009 to 2015, with a mean of 51.3 cases per year (raw incidence: 11.6/million/year), declining in the 2016-2018 years to 33.3 cases per year (raw incidence: 7.5/million/year). Conclusions With such discrepancy of cases overtime being partially explicable, number of new MRONJ cases per year are consistent with those observed in a previous study [2003-2008] in the same region, being instead higher than those reported in other populations. Key words: Osteonecrosis of the jaw, bisphosphonates, zoledronic acid, denosumab, antiangiogenic drug, incidence.

Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

“…In the case of systemic diseases, excluding those involving the use of these drugs, cardiovascular diseases and rheumatoid arthritis are highlighted [ 77 , 78 , 79 ]. Among the medical factors: chemotherapy, corticosteroids, smoking vitamin D deficiency, renal dialysis, anemia, Paget’s disease of bone, erythropoietin therapy, cyclophosphamide therapy, alcohol intake, and obesity are the most frequently reported [ 80 , 81 , 82 ]. Due to the scarce number of longitudinal studies involving this outcome, results make it difficult to quantitatively assess the thresholds for the level of damage of each of them individually [ 83 ].…”

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

“…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]. Although bisphosphonates are the drugs most frequently associated with MRONJ, there is a growing range of non-antiresorptive medications implicated in MRONJ development [23].…”

“…It can cause serious functional disturbance, morbidity, and adversely impact quality of life [1]. Although uncommon, MRONJ is in fact not a rare adverse event in myeloma patients; therefore, continuous monitoring and vigilance is essential from haemato-oncologists, and dental and oral maxillofacial specialists [2].…”

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

“…From the 25 studies that were included for full-text analysis, 14 were excluded; six studies only reported a single arm MRONJ case series or a case control study from which prevalence could not be assessed, [32][33][34][35][36][37] seven studies did not include/specify any AA therapy, [38][39][40][41][42][43][44] and one record was a conference abstract for which a full text was included from the original search. [45] Finally, a total of 11 full texts with extractable data were included in the qualitative and quantitative syntheses.…”