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.
Patient A was a 73-year-old white male who was diagnosed with RCC in 2000 and subsequently underwent a left radical nephrectomy. He went on to have multiple locoregional recurrences in the nephrectomy bed and in the lower pole of the right kidney. By January of 2007, he had involvement of the pancreatic tail and the left adrenal gland as well. He was evaluated at our medical center in March of 2007. He was restaged at that point and it was confirmed that he had no disease outside of the abdomen, so he was offered radical resection of his disease with curative intent by surgical oncology, but the patient declined. Therefore, he was started on sunitinib 50 mg daily for 4 weeks of a 6 week cycle, and an MRI in July 2007 showed decrease in the size of the tumor in the left renal bed and the pancreatic mass and right renal pole mass remained stable. Imaging after 24 weeks of sunitinib showed stable disease in known sites. His disease remained stable until imaging performed in April of 2008, after 36 weeks of treatment, showed clear enlargement of the renal fossa mass. The patient was then started on temsirolimus 25 mg IV weekly for second-line therapy. The patient had thrombocytopenia, worsening of lipid profile, and elevated blood glucose levels on temsirolimus that required a 20% dose reduction. After 12 weeks, CT scan showed pneumonitis consistent with mTOR inhibitor induced pneumonitis, a possible new lung metastasis, and progression of disease in the liver and renal fossa. Single agent bevacizumab 10 mg/m2 given every 2 weeks was started for third-line therapy and restaging every 3 months showed continued stable disease. The patient enjoyed 12 months of stable disease on single agent bevacizumab. It was stopped despite stable disease due to development of osteonecrosis of the jaw and patient request. The patient subsequently progressed rapidly and expired while off therapy.