The standard treatment for medication-related osteonecrosis of the jaw (MRONJ) is surgery. However, reports on the appropriate extent of bone resection are few. We aimed to examine the relationship between the extent of bone resection and postoperative outcomes in patients with mandibular MRONJ. The clinical and imaging findings and treatment outcomes of 206 patients (258 surgeries) with mandibular MRONJ undergoing surgery were reviewed. Imaging findings were evaluated using computed tomography (CT) to sequestrum, osteolysis, periosteal reaction, and mixed-type osteosclerosis, and determine the extent of resection. In some cases, samples were taken from within the bone, and real-time polymerase chain reaction was used to confirm the presence of bacteria and fungi. The three-year cumulative cure rate was 81.7%. Patients with malignant tumors showing no osteolysis and undergoing sequestrum removal or marginal mandibulectomy had significantly worse prognosis than those with osteoporosis showing osteolysis and undergoing segmental mandibulectomy. Furthermore, patients with residual osteolysis, periosteal reactions, and mixed-type osteosclerosis on CT were more likely to develop recurrence. Eleven patients showed no osteolysis on CT images. Patients with cancer administered with high-dose denosumab had significantly poorer prognosis. Bacteria and fungi were also detected in samples obtained from gap-type periosteal reaction and mixed-type osteosclerosis. Surgery for MRONJ requires resection of the infected bone. Aside from the osteolysis area, the gap-/irregular-type periosteal reaction and mixed-type osteosclerosis must also be included in the resection area. Methods for determining the extent of bone resection in MRONJ without osteolysis are a future challenge.

Bone morphogenetic protein-2 (BMP-2) has diverse functions and is especially important in bone and cartilage development. Recombinant human BMP-2 (rhBMP-2) is an osteoinductive growth factor that has been clinically applied as a bone graft substitute. However, high-dose rhBMP-2 can cause complications such as induction of significant swelling that can endanger the patient’s life. Atelocollagen sponge (ACS) is the commercially provided standard carrier of rhBMP-2 in clinical applications. However, a large concentration of rhBMP-2 is required to be clinically effective with ACS as the carrier. Octacalcium phosphate/collagen (OCP/Col) has been shown to be an excellent bone substitute compared with other bone substitute materials such as hydroxyapatite or β-tricalcium phosphate due to its biological properties. In this study, we evaluated the use of OCP/Col as a carrier to minimize the effective dose of rhBMP-2. ACS or OCP/Col discs impregnated with different rhBMP-2 concentrations were implanted in mice calvarial bone defects. Morphological analysis with micro-CT both at 4 and 6 weeks post-implantation showed homogenous hard tissue formation in the defects of the OCP/Col group at all rhBMP-2 concentrations tested (0, 0.25, 0.50, or 1.00 μg). In contrast, ACS alone or with 0.25 μg of rhBMP-2 showed almost no bone formation. However, bone mineral density in all groups of ACS and OCP/Col was not dependent on rhBMP-2 concentration. Histological evaluation indicated that bone formation progressed depending on rhBMP-2 concentration in the defects of both the ACS and OCP/Col groups, although the newly formed bone area was significantly higher in the OCP/Col group than in the ACS group. These results indicate that OCP/Col could be an effective carrier of rhBMP-2, minimizing the application dose of rhBMP-2 in clinical settings and avoiding the complications caused by high-dose rhBMP-2.

One of the causes of ventilator-associated pneumonia (VAP) is aspiration of oropharyngeal fluid containing pathogenic microorganisms into the lower respiratory tract. In this study, we aimed to investigate whether antibiotic ointment applied to the oral cavity can reduce the number of bacteria in the fluid on the cuff of a tracheal cannula. Tetracycline ointment was applied intraorally once to a patient under endotracheal intubation by postoperative tracheostomy for oral cancer. The tetracycline concentrations in the oropharyngeal fluid and fluid on the cuff of tracheal cannula were determined by bioassay, and the total viable bacterial count was determined by delayed real-time polymerase chain reaction developed by the authors from before to 6 h after application. A total of seven patients were enrolled. Very high antibiotic concentrations were maintained, ranging from 481 μg/ml to 2060 μg/ml in oropharyngeal fluid and from 267 μg/ml to 858 μg/ml in fluid on the cuff from 1 h to 6 h after application. Compared to the pre-application results, the inhibition rates of viable bacteria were 80.0–97.7% for oropharyngeal fluid and 47.6%–91.9% for fluid on the cuff at 1–6 h after application, indicating that antibiotic ointment can inhibit bacteria entering the lower respiratory tract for a long period of time in intubated patients. Oral application of antibiotic ointment reduced the number of bacteria entering the lower respiratory tract, suggesting that it may be useful in the prevention or treatment of VAP.

Surgical treatment has recently been recommended as a standard therapy for medication-related osteonecrosis of the jaw (MRONJ). However, no established methods exist for determining the extent of bone resection. We aimed to compare preoperative computed tomography (CT) and magnetic resonance imaging (MRI) findings with the histopathological findings of resection materials in patients with MRONJ undergoing surgery. This was a retrospective, observational study. We analyzed the preoperative CT and MRI findings, histopathological characteristics of the resected materials, and treatment outcomes of 14 patients with MRONJ who underwent segmental mandibulectomy at Department of Oral and Maxillofacial Surgery, Nagasaki University Hospital. Areas showing osteolysis, gap-type or irregular-type periosteal reactions, and mixed-type osteosclerosis on CT were histologically confirmed to contain osteomyelitis or necrotic bone. On MRI, MRONJ lesions exhibited low signal intensity on T1-weighted images (T1WI) and variable signal intensities on T2-weighted images (T2WI). The extent of MRONJ lesions was difficult to delineate using T1WI and T2WI. In contrast, high signal intensity on short tau inversion recovery (STIR) images accurately reflected the extent of histologically confirmed osteomyelitis. Osteomyelitis is present in areas with osteolysis, gap-type or irregular-type periosteal reactions, mixed-type osteosclerosis on CT, and high STIR signal intensity on MRI features. These findings may serve as reliable references for determining the extent of bone resection during surgery.

Local infections, such as periodontal disease or apical lesions, and invasive dental procedures, such as tooth extraction, are thought to trigger medication-related osteonecrosis of the jaw (MRONJ) development. However, some cases of MRONJ develop without any obvious odontogenic triggers. We conducted a retrospective study to clarify the characteristics of non-odontogenic MRONJ. We retrospectively reviewed data of 229 patients with mandibular MRONJ who underwent surgery. Based on imaging findings, we classified MRONJ as odontogenic MRONJ involving a dental infection and non-odontogenic MRONJ with no dental involvement. Clinical and imaging findings and treatment outcomes of both types of MRONJ were compared. Overall, 193 patients were classified as having odontogenic MRONJ and 36 as having non-odontogenic MRONJ. Non-odontogenic MRONJ was slightly more common among patients with malignancies who received denosumab; however, the difference was not significant. Univariate and multivariate analyses showed that patients with MRONJ with non-odontogenic triggers had significantly poorer treatment outcomes than their counterparts. Non-odontogenic MRONJ exists without the involvement of odontogenic infection as a cause of MRONJ. Compared with that in odontogenic MRONJ, the treatment outcome in non-odontogenic MRONJ is poor. Further studies are required to clarify the true nature of non-odontogenic MRONJ.