Reconstruction of continuity defects following osteonecrosis in multimorbid patients is challenging. In all cases of the predescribed palliative treatment method for alloplastic mandible reconstruction, plate fractures were detected in follow-up. We hypothesized that a modification could avoid these fractures, leading to stable long-term results.
This retrospective study compares the original method with a modification using single, laser-sintered CAD-CAM plates instead of manually bent miniplates. The predescribed shuttering technique was used to reconstruct the mandible in its original shape with bone cement.
Uneventful wound healing was observed in 86% of the cases after modification of the method. No implant or plate fracture occurred.
The presented method should be considered as a treatment option for mandible reconstruction in elderly, multimorbid patients in palliative situations. The results of this study suggest that the modification of the method leads to significantly improved long-term stability. Donor site morbidity is avoided with this method of palliative surgery.

We investigated the incidence/trend of osteonecrosis of the jaw by antiresorptive agent dose over a 5-year period in Kure city, Japan. The incidence was 24 times higher among osteoporosis patients with low-dose agents and 421 times higher among cancer patients with high-dose agents than in the population without agents.
OBJECTIVE: We launched the registry system of osteonecrosis of the jaw (ONJ) cases in 2015 to investigate the trend in ONJ incidence. The purpose of our study was to estimate the ONJ incidence among patients with antiresorptive agent use by dosage and people without antiresorptive agent use in Kure and its trend from 2016 to 2020.
METHODS: From 2016 to 2021, 98 eligible ONJ patients were enrolled. Medication-related ONJ (MRONJ) was diagnosed based on the American Association of Oral and Maxillofacial Surgeons criteria. The annual number of those with and without antiresorptive agents was obtained from the claims database. Antiresorptive agents used for cancer and osteoporosis patients were defined as high- and low-dose medications, respectively.
RESULTS: The annual incidence of high-dose MRONJ was 2305.8 per 100,000 and that of low-dose MRONJ was 132.5 per 100,000, while the ONJ incidence among people without antiresorptive agents was 5.1 per 100,000. The incidence ratio was 23.6 (p < 0.001, 95% confidence interval (CI) 13.3-41.8) among osteoporosis patients who used low-dose antiresorptive agents and 420.6 (p < 0.001, 95% CI 220.8-801.4) among cancer patients who used high-dose agents compared with people who did not use these agents. MRONJ incidence increased from 2016 to 2020, but the incidence of high-dose MRONJ decreased, although this was nonsignificant.
CONCLUSIONS: We demonstrated the incidence and trend of ONJ by antiresorptive agent dose over a 5-year period in Kure after launching the multiprofession study. This collaborative study for the early detection and prevention of ONJ will continue.

Background and Objectives: The purpose of this study was to evaluate the impact of surgical and conservative, non-surgical treatment on general health-related (QoL) and oral health-related quality of life (OHRQoL) in patients suffering from AAOMS stage I MRONJ. Materials and Methods: In the course of this prospective clinical study, QoL and OHRQoL using QLQ-C30 and QHIP G14 questionnaire were longitudinally assessed in N = 174 prospectively enrolled patients with indication of treatment of MRONJ stage I over a period of 12 months. Patients received conservative or surgical treatment. The measurement time points were preoperatively (T0), 12 weeks (T1), 6 months (T2) and 1 year after operation (T3). Results: For OHRQoL, no significant (p > 0.05) differences were found between both treatment groups for all timepoints (T0-T3). In the surgical treatment group, OHIP scores of T1, T2 and T3 were significantly lower than baseline measures (T0) (T0-T1 (2.99, p = 0.024), T0-T2 (5.20, p < 0.001), T0-T3 (7.44, p < 0.001)). For conservative treatment group OHIP, scores of T2 and T3 were significantly lower than baseline measures (T0) (T0-T2 (9.09, p = 0.013), T0-T3 (12.79, p < 0.001)). There was no statistically significant effect of time on QLQ-C30 scores in both groups (surgical treatment: F(3, 174) = 1.542, p < 0.205, partial η2 = 0.026; conservative treatment: F(3, 30) = 0.528, p = 0.667, partial η2 = 0.050). QLQ-C30 scores turned out to be significantly lower in the non-surgical group at T1 (p = 0.036) and T3 (p = 0.047) compared to the surgical treatment group. Conclusions: Surgical and conservative treatment of MRONJ stage I significantly improves patients\' OHRQoL. Surgical treatment is superior to conservative treatment of MRONJ stage I regarding general QoL. Therefore, surgical treatment of MRONJ stage I should not be omitted for QoL reasons.

Background: The role of medication-related osteonecrosis of the jaw (MRONJ) as a dento-maxillo-facial pathology is becoming increasingly important due to its growing prevalence. The success of preventive and therapeutic measures relies mainly on the dentist\'s ability to correctly diagnose the disease. Methods: The aim of this study was to evaluate the skills of dental students of different educational levels in choosing the correct stage, diagnostics, and treatment option for MRONJ based on clinical and radiographic imaging (panoramic radiograph, CBCT). The study was designed as a cross-sectional cohort study. Twenty dental students were asked to complete a questionnaire in their third and fifth year of studies in which they had to correctly stage the disease, choose the radiological diagnostics and recommend the treatment. The control group contained experienced oral and maxillofacial surgeons. Results: With an overall performance of 59% (third year: 145.2/248 points; fifth year: 145.3/248 points), no statistically significant difference between the educational levels could be observed. The classification based on CBCT imaging was significantly more often correct compared to panoramic radiographs (p < 0.001). Conclusions: This study highlights students\' lack of knowledge in staging, diagnostics, and treatment of MRONJ, even though the CBCT positively affected decision-making. No significant increase in knowledge could be confirmed through clinical education. This study highlights the need for students to catch up on MRONJ diagnostics and treatment planning. Further expansion of teaching in this disease\'s context and X-ray diagnostics is needed.

Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.

OBJECTIVE: Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a \"bio-carrier\" for antibiotics previously applied intravenously.
METHODS: We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients\' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls.
RESULTS: Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing.
CONCLUSIONS: The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect.
CONCLUSIONS: We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a dreaded complication in patients with compromised bone metabolism. The purpose of the present study was to examine the occurrence of ARONJ and its related factors among patients with a history of antiresorptive therapy undergoing tooth extraction using preventive protocols at a Swiss university clinic. Data were retrospectively pooled from health records of patients having received a surgical tooth extraction between January 2015 and April 2020 in the Clinic of Cranio-Maxillofacial and Oral surgery, University of Zurich. A total of 970 patients received an extraction with flap elevation or wound closure during this period. A total of 104 patients could be included in the study. Furthermore, variables including age, gender, smoking, risk profile, choice, indication and duration of antiresorptive therapy, number of extractions, extraction site, surgical technique, choice and duration of antibiotics as well as the presence of postoperative inflammatory complications were assessed. Overall, 4 patients developed ARONJ (incidence of 3.8%) after tooth extraction at the same location, without previous signs of osteonecrosis. Preventive methods included predominantly primary wound closure using a full thickness mucoperiosteal flap and prolonged perioperative antibiotic prophylaxis. In accordance with current literature, the applied protocol showed a reliable outcome in preventing ARONJ when a tooth extraction is required.

OBJECTIVE: We aimed to predict the possibility of patients with stage I and II anti-resorptive agent-related osteonecrosis of the jaw (ARONJ) developing resistance to our treatment protocol by evaluating their clinical and imaging factors.
METHODS: We enrolled 58 patients with ARONJ who underwent imaging modality. As objective variables, we considered the healing, stage-down, and stable stages as successful outcomes, and the stage-up stage as resistant-to-treatment. As explanatory variables, we investigated the clinical and imaging factors. Furthermore, we examined stage-down as an improvement outcome to compare with the stable and stage-up stages, which were considered as no-improvement outcomes. We conducted unpaired between-group comparisons on all explanatory variables using χ2 tests for independence.
RESULTS: Among 58 patients, the treatment was successful in 53 (91.4%); however, the disease was resistant in five (8.6%). Among the clinical factors, the resistant patients had a longer duration of administration of bone-modifying agents (BMAs) (cut-off: 1251 days, p = 0.032, odds ratio = 11.2, 95% confidence interval 1.115-122.518). In addition, the target disease that was being treated bone metastasis of malignant tumor was the only significant refractory factor (p = 0.024, OR: 3.667 95% CI 1.159-11.603) CONCLUSIONS: A combination of metabolic and morphological imaging modalities may be useful for oral surgeons to evaluate the disease activity and predict course of refractory ARONJ.

OBJECTIVE: The aim of our study was to describe microbial flora associated with MRONJ and characterize the susceptibility of pathogens to help guide an effective empiric antibiotic treatment in these patients.
METHODS: A retrospective, single-center analysis was performed, using 116 bone samples from 98 patients. The bone samples were homogenized and subjected to routine culture methods. Growing bacteria were differentiated to the species level using whole-cell mass spectrometry and subjected to susceptibility testing.
RESULTS: A highly diverse microbial flora was detected in necrotic bone, with a simultaneous presence of two or more bacterial species in 79% of all patients. In at least 65% of samples, gram-negative isolates were detected. Therefore, bacterial species resistant against β-lactamase inhibitors were present in at least 70% of all patients.
CONCLUSIONS: The empiric choice of antibiotics in MRONJ patients should consider the high rate of gram-negative bacteria and resistance against β-lactam antibiotics.
CONCLUSIONS: According to recent guidelines and recommendations, systemic antibiotic treatment is a key component in the treatment of all stage 2 and 3 MRONJ patients. We recommend using fluoroquinolones for empiric treatment and emphasize the use of bacterial cultivation and susceptibility testing to enable an effective antibiotic treatment.

BACKGROUND: Over the past two decades, antiresorptive agent-related osteonecrosis of the jaw (ARONJ) has become a growing concern. We examined the incidence of ARONJ and identified its risk factors in lung cancer patients in the real-world clinical setting. To our knowledge, we are the first to do so.
METHODS: We retrospectively analyzed lung cancer patients with bone metastases who had received anti-resorptive agents (zoledronate or denosumab) at the National Hospital Organization Kyoto Medical Center from October 2012 to September 2018. All ARONJ cases were diagnosed by the dentists according to the established diagnostic criteria.
RESULTS: A total of 171 patients were reviewed, 13 (7.6%) of whom experienced ARONJ. Among the 13 patients, six (46.2%), four (30.8%) and three (23.1%) had adenocarcinoma, squamous carcinoma and not otherwise specified, respectively. ARONJ was stage 2 in three (23.1%) patients and stage 3 in 10 (76.9%). More cycles of antiresorptive agents (odds ratio [OR] = 11.54; 95% confidence interval [CI], 2.47-53.99; P < 0.01), use of immune checkpoint inhibitors (ICIs; OR = 5.05; 95% CI, 1.56-16.37; P < 0.01) and longer survival duration (≥2 years; OR = 12.16; 95% CI, 3.17-46.65; P < 0.01) were independently associated with ARONJ in a multivariate analysis.
CONCLUSIONS: The incidence of ARONJ was relatively high in lung cancer patients with bone metastases. When using antiresorptive agents, oncologists should closely monitor patients for ARONJ during the course of treatment and regularly consult with dentists, especially in patients receiving ICIs.