A 79-year-old male patient was referred on December 2015 to the Turin Oral Health Department (Dental School) for a baseline exam before starting therapy with bisphosphonates; clinical examination revealed an already present bone exposition approximately 3 mm × 1 mm in the left posterior mandible, in correspondence of the mylohyoid line, asymptomatic ().\nThe history from the patient included colon adenocarcinoma that was diagnosed and treated surgically on October 2008 (stage pT2 pN1 G3). Subsequently the patient underwent adjuvant chemotherapy with the XELOX scheme (capecitabine and oxaliplatin).\nHe also suffered from hypertension and prostatic hyperplasia, and had been submitted for coronary angioplasty due to cardiac ischemia in 2007.\nOn September 2010, the patient underwent surgery of lung nodules (pathology revealed a lung hamartoma and some metastases of carcinoma of colorectal origin). From November 2010 to April 2011, he received postoperative chemotherapy with the FOLFIRI scheme (irinotecan, fluorouracil, folinic acid).\nAfter the lung progression of the disease, from January 2012 to March 2012 he underwent FOLFOX chemotherapy (oxaliplatin, fluouracil, folinic acid) which was stopped for an allergic reaction to oxaliplatin. In April 2012, he started chemotherapy with irinotecan together with bevacizumab (7.5 mg/kg every 14 days) for seven cycles (until June 2012). After a drug holiday, on October 2013 the patient restarted chemotherapy (without bevacizumab) for five other cycles. On March 2014, he underwent stereotactic radiation therapy of two residual lung nodules.\nDue to a new lung progression, on October 2014 he started irinotecan and bevacizumab again (same doses) for 12 cycles, until April 2015. He continued bevacizumab only (maintenance therapy) until October 2015 for 10 courses, until reaching a total of 22 bevacizumab administrations in this second course.\nOn October 2015, bone metastases were diagnosed and he started therapy with mitomycin and fluorouracil.\nOn 1 October 2015, the patient had undergone tooth extraction of the two mandible canines and of the second left mandible molar due to excessive mobility at a private dentist office. Tooth extractions were conducted under antibiotic coverage (amoxicilline plus clavulanic acid 1 g every 12 h for six days).\nOn December 2015, the patient was referred to the Turin Oral Health Department (Dental School) for a baseline evaluation in order to start intravenous bisphosphonate therapy, after diagnosis of bone metastases. At the time of the visit the patient was completely edentulous, and he was a wearer of two dentures. As written before, intraoral examination showed a bone exposition approximately 3 mm × 1 mm in the left posterior mandible, in correspondence of the mylohyoid line, asymptomatic (). Trauma from the dentures was excluded. The surrounding soft tissue appeared ulcerated and necrotic, with no evidence of infection, so a cone-beam computer tomography (CBCT) was requested in order to investigate the real dimensions of the necrosis and to exclude metastatic lesions. CBCT revealed a minor cortical sclerotic bone lesion and a residual of the post-extraction socket without images of bone sequestra (a–c).\nThe patient underwent six administrations of low level laser therapy (LLLT), twice a week, and then he was re-evaluated. At the end of January 2016, the patient underwent a contrast-enhanced computer tomography (CT) scan, which excluded definitively the hypothesis of a metastatic lesion. At that date, the lesion was still asymptomatic, but an oral fistula appeared in the second left molar region (). The diagnosis of MRONJ was confirmed.\nA new antibiotic therapy was prescribed (amoxicilline plus clavulanic acid 1 g every 8 h for six days and metronidazole 500 mg every 8 h for six days) in combination with a chlorhexidine 0.2% oral rinse. After a week the patient expelled a bone sequestrum approximately 4 mm × 2 mm large as well as referred mucosal healing at the bone exposure site and disappearance of the oral fistula.\nOn 3 March 2016, the patient was re-evaluated and at intraoral examination both the bone exposure and the oral fistula were completely healed ().\nAt six months from the event, there were no recurrences. Further follow-up visits are planned.
A 60-year-old man was visited at the Alessandria Hospital Oncology Unit on August 2011 for a routine visit before a chemotherapy administration (FOLFOX scheme and bevacizumab), complaining of left mandible pain (VAS: visual analogue scale, score 6) and an oral mucosal break; the oral examination revealed a lingual-side bone exposure, 1 cm in diameter (no photo available). Four weeks before, he had started treatment with chemotherapy associated with bevacizumab for the second time.\nHis cancer history had begun on February 2010 with the diagnosis of rectal cancer and lung metastases. He underwent treatment with pelvic radiotherapy and simultaneous chemotherapy (oxaliplatin and fluorouracil in a continuous infusion) and then rectal surgery (on July 2010); additional chemotherapy (FOLFIRI) was administered in August 2010. Some pulmonary metastases were surgically removed on November 2010 but residual disease was still present in a chest postoperative CT scan.\nHe received chemotherapy (FOLFIRI scheme) and bevacizumab (5 mg/kg day 1 every 14 days) between December 2010 and March 2011 (eight cycles over four months). Due to pulmonary progression of the disease, he underwent a short treatment with an experimental agent in another cancer center, suspended on July 2011 due to the diagnosis of brain metastases, treated with radiotherapy. He then started new chemotherapy (FOLFOX scheme) with bevacizumab again.\nHis dental history revealed that he had been submitted for left mandible third molar (3.8) extraction at a private dental office on January 2011 (during the first bevacizumab treatment) without notifying the treating oncologist; the patient complained about incomplete and delayed socket closure after extraction.\nOn August 2011, at an oncology unit visit shortly after the start of the second course of bevacizumab therapy (two administrations), a painful mandible bone exposure was noted and the patient was referred to the Alessandria Hospital ONJ multidisciplinary team; antibiotics (amoxicilline plus clavulanic acid 1 g every 8–12 h and metronidazole 500 mg every 12 h) in combination with a chlorhexidine 0.12% oral rinse were prescribed, with immediate pain reduction. Rx ortopantomography showed no signs of osteolysis but just the profile of the residual socket at the extraction site (). A CT scan without contrast showed a mandible bone cortical lesion in the previous tooth extraction site, 7 mm × 4 mm in size (a–c). Spontaneous expulsion of a bone fragment was referred by the patient two weeks later. The patient was not further visited by the ONJ multidisciplinary team due to death shortly after an episode of pulmonary embolism on October 2011.