Is Medication-Related Osteonecrosis of the Jaws (MRONJ) Associated to Cyclin-Dependent Kinase (CDK) 4/6 Inhibitors? A Word of Cautiousness. Comment on Marcianò et al. Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association. Int. J. Environ. Res. Public Health 2020, 17, 9509.

Marcianò et al. launched an alert in this journal about a possible association between medication-related osteonecrosis of the jaws (MRONJ) and cyclin-dependent kinase (CDK) 4/6 inhibitors in breast cancer patients [...].

Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ) Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases.

Medication-induced Osteonecrosis of the Jaw (MRONJ) has been reported not only after use of antiresorptive agents (bisphosphonates and denosumab), but also in cancer patients receiving antiangiogenic agents, alone or combined with antiresorptive drugs. We report two cases of MRONJ observed in colorectal cancer patients after bevacizumab therapy only. MRONJ was diagnosed, respectively, two and seven months after a tooth extraction; both the patients had received two courses of bevacizumab infusions (for a total of 29 and 10 administrations, respectively). We discuss if tooth extraction during or after antiangiogenic therapy could be a potential trigger of MRONJ, but also if an underlying bone disease not evident before oral surgery might be a possible cause. A careful drug history has to be registered by dental specialists in cancer patients before oral surgery and adequate imaging might be obtained to avoid a delayed diagnosis.

Osteonecrosis of the Jaws (ONJ) after Bisphosphonate Treatment in Patients with Multiple Myeloma: Decreasing ONJ Incidence after Adoption of Preventive Measures.

Bisphosphonates (BPs) are administered to Multiple Myeloma (MM) patients with bone lytic lesion. Osteonecrosis of the Jaw (ONJ) is a complication reported since 2003 in patients treated with intravenous (IV) BPs such as zoledronic acid and pamidronate, with 6%-26.3% frequency in early literature series, before some preventive measures were recommended. We evaluated the occurrence of ONJ with and without dental preventive measures in MM patients treated with BPs in our centre between 1996 and 2015. Since 2005, MM patients (already under treatment or before treatment) underwent a baseline mouth assessment (dental visit, Rx orthopantomography, and eventual tooth avulsion or dental care if necessary) and were followed by a multidisciplinary team. We reviewed the charts of 119 MM patients receiving IV BPs, classified into 3 groups: (a) "historic group" (21 patients who had started BP treatment in years before the awareness of ONJ); (b) "screening group" (20 patients starting BPs without baseline evaluation); and (c) "prevention group" (78 patients starting therapy only after baseline preventive assessment and eventual dental care measures). ONJ was observed in 3/21 patients (14.2%) from group a, in 2/20 patients (10%) from group b, and in no patients from group c (0%). Notably, the median number of IV BP administrations decreased after 2005. Our data confirmed a meaningful reduction of ONJ risk in MM patients treated with BPs if preventive measures are applied. Both implementation of prevention measures and reduction of cumulative doses of IV BPs could have contributed to a decreased incidence of ONJ.

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 / Un estudio observacional multicéntrico sobre osteonecrosis relacionada con medicamentos de la mandíbula (MRONJ) en pacientes con cáncer avanzado y mieloma de una red contra el cáncer en el noroeste de Italia

Background: Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) related to cancer and myelomatreatments is undetermined, with scarce data varying from 2 to 7.8/million/year in limited investigated popula-tions. A 9-years [2009-2018] regional-wide survey was conducted, deploying the North-Western Italy Cancer Net-work (“Rete Oncologica Piemonte e Valle d’Aosta”), to assess number and main characteristics of MRONJ casesamong 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 July2015 to December 2018, data were collected prospectively. Number of new MRONJ cases per year, underlyingdisorder, 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 antiangiogenicdrugs. 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 casesper 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 peryear are consistent with those observed in a previous study [2003-2008] in the same region, being instead higher thanthose reported in other populations.(AU)