Risk of healing impairment following tooth extraction in patients administered with antiresorptive and non-antiresorptive polypharmacy.

INTRODUCTION: Lack of evidence existed related to the essential role by which anticancer medications alone or in combination with other polypharmacy would be accountable for wound healing impairment post-dental extraction. The following study was conducted to assess the influence of antiresorptive (AR) and non-antiresorptive (non-AR) drugs and other patient-related risk factors on wound healing status following tooth extraction. MATERIAL AND METHODS: A total of 353 patients (age range: 40-90 years, average age: 67.4 years, clinical and radiological follow-up) were recruited. All the patients were divided into three groups, which included, patients used polypharmacy with non-AR drugs, polypharmacy with a combination of AR + non-AR drugs, and the control group. Based on time of healing, the outcome was defined as, normal healing, delayed healing, and Medication-related osteonecrosis of the jaw (MRONJ). The polypharmacy score was categorized depending on the sum of the number of administered medications. RESULTS: The odds of delayed healing were significantly higher in 80+ years old patients (OR=6.98, 95 %CI:2.45-19.88, p = < 0.001) administered with AR+ non-AR drugs (OR=14.68, 95 %CI:4.67-46.14, p = < 0.001), having a major polypharmacy score (OR= 15.37, 95 %CI:4.83-48.91, p = < 0.001). On the contrary, patient administered with non-AR drugs (OR=11.52, 95 %CI: 4.45-29.83, p = < 0.001) with hyper polypharmacy (OR=58.86, 95 %CI:25.03-138.40, p = < 0.001) were significantly more likely to develop MRONJ. Smoking and extraction sites showed no significant impact on wound healing impairment. DISCUSSION: Wound healing status in patients administered with both non-AR and AR+ non-AR polypharmacy was significantly impaired following tooth extraction. Other risk factors, such as increased age and high polypharmacy scoring, also significantly contributed towards the occurrence of delayed healing and MRONJ.

Navigating the complexities and controversies of medication-related osteonecrosis of the jaw (MRONJ): a critical update and consensus statement.

OBJECTIVES: To provide a critical update identifying the knowledge gaps and controversies in medication-related osteonecrosis of the jaw (MRONJ) within the Belgian healthcare context and outline opportunities for improvement and research in these areas. METHODS: A literature review was performed to identify guidelines from international clinical societies in oncology or oral and maxillofacial surgery on diagnosing, preventing, and treating MRONJ. The recommendations were critically assessed in light of recent developments in the field and confronted with the clinical experience of experts. RESULTS: Despite progress in the diagnostic criteria of MRONJ, the continued need for an 8-week timeout period should be reconsidered. Furthermore, 3D imaging techniques should be introduced to improve diagnosis and staging. The staging system remains ambiguous regarding Stage 0 MRONJ, and ongoing confusion exists regarding the term non-exposed MRONJ. The prevention of MRONJ should be tailored, considering the individual patient's risk of MRONJ, frailty, and life expectancy. More research seems needed into the efficacy and safety of drug holidays, considering the risks of rebound remodeling on fractures. With renewed interest in surgical and adjunct management techniques, adequately designed clinical studies are needed to help translate trial outcomes into universally applicable treatment guidelines taking into account individual patient characteristics. CONCLUSIONS: Important knowledge gaps remain and hamper the development of clinical guidelines. Several controversies were identified where consensus is lacking, and further harmonization between stakeholders is necessary. Finally, the need for randomized controlled comparative clinical trials in MRONJ resonates harder than ever to identify the best treatment for individual patients.

A 16-year retrospective study of vascular anomalies in the head and neck region.

Depending on the diagnostic modality, the classification of vascular anomalies varies and so does the nomenclature. The 'International Society for the Study of Vascular Anomalies' (ISSVA) is the most widely accepted classification in the literature and is mainly based on the radiologic and clinical presentation. The aim of this article is to review the clinical practice of diagnosis and treatment of vascular anomalies in the head and neck region in a university hospital, with special focus on the nomenclature. All patients with a vascular anomaly presenting to the department of oral and maxillofacial surgery were reviewed in a retrospective manner. Nomenclature, diagnostic process, lesion characteristics, treatment and outcome were examined. The lesions were (re)classified according to the ISSVA classification. A total of 185 patients were identified, of which 12.4% (n = 23) had a congenital anomaly. After reclassification, the most common lesions were venous malformations (n = 47, 25.4%), followed by lobular capillary hemangiomas (n = 17, 9.2%). A group of 39 anomalies could not be further specified. One hundred and one patients (54,6%) received treatment, of which 93 were treated surgically (92,1% of treated patients). Endovascular treatment was considered in 41 patients but applied in only eight. This strict selection led to a low a complication rate. We provide an overview of the clinical practice in the management of vascular anomalies in a university hospital. The histology report is a source of miscommunication because clinicians use the ISSVA classification, while pathologists use the WHO classification. Every professional involved should be aware of the differences in classification and nomenclature.

Risk of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents - A retrospective study of 240 patients.

This study investigated the incidence, risk factors, and outcome of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents for osteoporosis or bone metastases. 240 patients with a median drug exposure of 43 months were retrospectively studied. The incidence of MRONJ after dental extraction in the osteoporosis cohort was 2.7 % per person-year (95 % CI 1.6-4.6 %) (n = 13/126), and for the bone metastases cohort 26.4 % per person-year (95 % CI 20.4-34.2 %) (n = 58/114). 92 % of MRONJ cases were stage 1. Dental infection as the reason for extraction increased the osteonecrosis risk in the osteoporosis (OR 22.77; 95 % CI 2.85-181.62; p = 0.003) and bone metastases cohorts (OR 2.72; 95 % CI 1.28-5.81; p = 0.010). Using leukocyte and platelet-rich fibrin reduced this risk by 84 % (p = 0.003), as did antibiotics use by 86-93 % (p = 0.013). Within the bone metastases cohort, an interval since last administration of at least 3 months reduced risk of MRONJ (OR 0.83; 95 % CI 0.72-0.97; p = 0.018). Mucosal healing occurred in 11/13 patients (84.6 %; 95 % CI 54.5-98.1 %) with osteoporosis and 31/58 patients (53.4 %; 95 % CI 40.0-66.7 %) with bone metastases. In conclusion, though the MRONJ risk in this selected population taking antiresorptive agents and presenting to the Oral Maxillofacial Surgery clinic for a dental extraction is considerable and higher in those with dental infections, preventive measures such as antibiotics and use of LRPF membranes may significantly reduce that risk.

Non-neoplastic salivary gland diseases in children: a 10-year review at a tertiary center.

OBJECTIVES: Non-neoplastic salivary gland diseases are rare in children. This paper aims to present the spectrum of encountered non-neoplastic salivary gland diseases at a tertiary center by describing the demographics, clinical characteristics, and outcomes in this patient population. METHODS: A review of electronic medical records was performed from 2010 until 2020. Relevant data were retrieved and charted according to the type of salivary gland disease. A comparison between diseases was made for demographics, presenting symptoms, treatment, and outcomes. RESULTS: Fifty patients with 11 different non-neoplastic salivary gland diseases were identified. Sialolithiasis was the most prevalent condition (12/50), with 83% localized in the submandibular gland. In contrast to gender, age, and symptoms, the location of pathology was significantly associated with the diagnosis (p < 0.001). In patients with sialolithiasis, a hybrid procedure (combined endoscopy and lithotomy) resulted in 100% resolution of symptoms. For (plunging) ranula, marsupialisation had a relative risk of recurrence of 9.6 compared to (partial) extirpation of the sublingual gland. CONCLUSIONS: Children with salivary gland diseases present with overlapping symptoms, making clinical diagnosis challenging. The present study may aid physicians and specialists in diagnosing the most prevalent conditions in children. Although no gold standards exist for their treatment, hybrid procedures (sialolithiasis) and subglingual gland extirpation (ranula) showed superior results over alternatives.

Indications and complications regarding titanium osteosynthesis in pediatric maxillofacial trauma: A scoping review and critical appraisal.

With the advent of biodegradable osteosynthesis material, titanium osteosynthesis for ORIF in pediatric maxillofacial trauma is not as indisputable as before. The aim of this study was to conduct a scoping review to assess the indications, complications of ORIF with titanium osteosynthesis material in pediatric maxillofacial trauma. A systematic search was conducted in PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, gray literature (ICTRP and clinicaltrials.gov) for studies published until April 2022. 3436 studies were screened and finally 13 articles, compromising a sample of 340 pediatric patients were included after full text reading. Reported complications were infection (6.5% of population), malocclusion (5% of population) and dental maleruption (8% of population). Influence on future growth could not be assessed due to short and heterogeneous follow-up periods. Eight of the thirteen studies concluded to a positive and predictable outcome using titanium ORIF for displaced/complex pediatric maxillofacial fractures. Results of this review suggest that titanium ORIF for maxillofacial fractures in the pediatric population is a reliable treatment. The surgeon must be committed to following these patients longitudinally. Interpreting the results should, however, be done with great care, as most articles have a medium to high risk of bias and limited follow-up.

Systemic Antibiotic Prophylaxis in Maxillofacial Trauma: A Scoping Review and Critical Appraisal.

Infection after maxillofacial trauma remains an important complication, with a significant socio-economic impact. While consensus exists that systemic antibiotic prophylaxis reduces the risk of infection in the management of maxillofacial fractures, the type, and duration remain controversial. Therefore, the purpose of this scoping review was to provide an overview of the current evidence that supports the use of prophylactic antibiotics in the treatment of maxillofacial fractures. A comprehensive literature search on 1 January 2022, in PubMed, Web of Science, Embase, and Cochrane, revealed 16 articles. Most studies focused on the duration of systemic antibiotic prophylaxis and compared a one-day to a five-day regimen. Included studies showed considerable variability in design and research aims, which rendered them difficult to compare. Furthermore, a variety of antibiotic regimens were used, and most studies had a short follow-up period and unclear outcome parameters. This scoping review demonstrates the lack of well-constructed studies investigating the type and duration of systemic antibiotic prophylaxis in the treatment of maxillofacial trauma. Based on the included articles, prolonging antibiotic prophylaxis over 24 h for surgically treated fractures does not appear to be beneficial. Furthermore, there is no evidence for its use in conservatively treated fractures. These results should be interpreted with caution since all included studies had limitations.

Sialendoscopy: A Four-Year Single Center Experience.

PURPOSE: Sialendoscopy is a relatively new technique designed to diagnose and treat benign obstructive salivary gland disease using a minimally invasive approach. The purpose of this study is to present our experiences regarding the use of sialendoscopy in the form of a 4-year, single center experience and to demonstrate its usefulness in oral and maxillofacial practice. METHODS: We collected data on patients who underwent sialendoscopy at the Oral-Maxillofacial Surgery Department of UZ Leuven between November 2015 and August 2019, including age, gender, sex, initial clinical presentation and symptoms, gland involvement, type of diagnostic investigations, diagnosis, localization of the obstruction, therapeutic intervention, surgeon, type of anesthesia, materials used, complications, secondary treatment, duration of follow-up, and outcome. Statistical analyses were performed, chi-squared was used to compare the different variables with P < .05 being considered significant. RESULTS: During the 4-year timeframe, a total of 44 patients (31 female, 13 male) underwent sialendoscopy in a total of 47 procedures. The average age at time of sialendoscopy was 47.4 years. The most frequent cause of obstruction was sialolithiasis (70%). Cone-beam computed tomography (CBCT) was the most accurate preoperative investigation for the diagnosis of lithiasis (57%). Symptom improvement occurred in 57.9% of patients, with a complication rate of 11%. None of the complications were permanent. CONCLUSION: Sialendoscopy can be considered safe and effective for both the diagnosis and treatment of benign obstructive salivary gland disease, with a useful place in oral and maxillofacial surgical practice. We recommend the inclusion of CBCT and/or ultrasound in the diagnostic workup prior to endoscopy.

Why do some extraction sites develop medication-related osteonecrosis of the jaw and others do not? A within-patient study assessing radiographic predictors.

PURPOSE: To compare radiographic predictors of medication-related osteonecrosis of the jaw in dental extraction sites. MATERIALS AND METHODS: Forty-one oncological patients undergoing intravenous or subcutaneous antiresorptive treatment, with a history of dental extraction visualised by panoramic imaging, were included in this retrospective study. Age-, sex- and extracted tooth-matched healthy patients who had previously undergone panoramic imaging were selected as controls (n = 57). A total of 288 extraction sites were independently evaluated by two oral and maxillofacial radiologists, who assessed eight distinct radiographic features. The radiographic features of extraction sites were noted to allow comparison between and within subjects regarding healing and osteonecrosis development. The association between radiographic findings, underlying dental disease and medication-related osteonecrosis of the jaw was also tested. The level of significance was set at 5%. RESULTS: Patients under antiresorptive treatment presented with widening of the periodontal ligament space, thickening of the lamina dura, sclerotic bone pattern, horizontal bone loss and periapical radiolucency with bone reaction (P ≤ 0.05). Development of medication-related osteonecrosis of the jaw was associated with altered bone pattern, angular bone loss, furcation involvement and unsatisfactory endodontic treatment (P ≤ 0.05). An association between medication-related osteonecrosis of the jaw and previous dental disease was also found, particularly for periapical lesions and endodontic-periodontal disease (P ≤ 0.05). CONCLUSIONS: Radiographic predictors of further development of medication-related osteonecrosis of the jaw in extraction sites include heterogeneous bone pattern, angular bone loss and furcation involvement. Extraction sites with underlying bony changes related to endodontic and endodontic-periodontal disease are more prone to development of medication-related osteonecrosis of the jaw.

Osteomyelitis, osteoradionecrosis, or medication-related osteonecrosis of the jaws? Can CBCT enhance radiographic diagnosis?

OBJECTIVE: To attempt defining differential radiographic diagnostic characteristics for osteonecrotic lesions using 2D as opposed to 3D images. MATERIALS AND METHODS: This was a cross-sectional study. Subjects presenting mandibular osteonecrotic lesions (osteomyelitis, osteoradionecrosis, and medication-related osteonecrosis of the jaws) were selected and compared to a group of age- and gender-matched controls, all having both cone-beam computed tomographic images (CBCT) and panoramic radiographs (PANO). Both imaging modalities (predictor variables) were evaluated by two radiologists that scored lesion presence, eight additional radiological features, and a composite severity index (outcome variables). For each pathologic condition, characteristic features were assessed in PANO and CBCT by the Wilcoxon signed-rank test. Regression tree analysis revealed the predictive value of PANO and CBCT (α = 5%). RESULTS: Overall, the predictive value of PANO reached 74%, while for CBCT it became 90%. Regarding the composite severity index, CBCT enabled to detect more subtle lesions. Also, CBCT imaging allowed showing more distinct radiographic diagnostic features as compared to PANO imaging, more specifically when distinguishing osteomyelitis from both other lesions. CONCLUSIONS: Cone-beam computed tomography enabled showing more differences in radiological features between distinct osteonecrosis disease entities. CBCT imaging might be a better contributor for the detection of early lesions and to monitor further pathological developments in the mandible.

Implant functionalization with mesoporous silica: A promising antibacterial strategy, but does such an implant osseointegrate?

OBJECTIVES: New strategies for implant surface functionalization in the prevention of peri-implantitis while not compromising osseointegration are currently explored. The aim of this in vivo study was to assess the osseointegration of a titanium-silica composite implant, previously shown to enable controlled release of therapeutic concentrations of chlorhexidine, in the Göttingen mini-pig oral model. MATERIAL AND METHODS: Three implant groups were designed: macroporous titanium implants (Ti-Porous); macroporous titanium implants infiltrated with mesoporous silica (Ti-Porous + SiO2 ); and conventional titanium implants (Ti-control). Mandibular last premolar and first molar teeth were extracted bilaterally and implants were installed. After 1 month healing, the bone in contact with the implant and the bone regeneration in the peri-implant gap was evaluated histomorphometrically. RESULTS: Bone-to-implant contact and peri-implant bone volume for Ti-Porous versus Ti-Porous + SiO2 implants did not differ significantly, but were significantly higher in the Ti-Control group compared with Ti-Porous + SiO2 implants. Functionalization of titanium implants via infiltration of a SiO2 phase into the titanium macropores does not seem to inhibit implant osseointegration. Yet, the importance of the implant macro-design, in particular the screw thread design in a marginal gap implant surgery set-up, was emphasized by the outstanding results of the Ti-Control implant. CONCLUSIONS: Next-generation implants made of macroporous Ti infiltrated with mesoporous SiO2 do not seem to compromise the osseointegration process. Such implant functionalization may be promising for the prevention and treatment of peri-implantitis given the evidenced potential of mesoporous SiO2 for controlled drug release.

A novel fully automatic design approach of a 3D printed face specific mask: Proof of concept.

The use of high quality facemasks is indispensable in the light of the current COVID pandemic. This study proposes a fully automatic technique to design a face specific mask. Through the use of stereophotogrammetry, computer-assisted design and three-dimensional (3D) printing, we describe a protocol for manufacturing facemasks perfectly adapted to the individual face characteristics. The face specific mask was compared to a universal design of facemask and different filter container's designs were merged with the mask body. Subjective assessment of the face specific mask demonstrated tight closure at the nose, mouth and chin area, and permits the normal wearing of glasses. A screw-drive locking system is advised for easy assembly of the filter components. Automation of the process enables high volume production but still allows sufficient designer interaction to answer specific requirements. The suggested protocol can be used to provide more comfortable, effective and sustainable solution compared to a single use, standardized mask. Subsequent research on printing materials, sterilization technique and compliance with international regulations will facilitate the introduction of the face specific mask in clinical practice as well as for general use.

Adjuvant therapies for MRONJ: A systematic review.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction caused by the use of antiresorptive antiangiogenic medication. Treating MRONJ is difficult and besides standard treatments, which are conservative medical and surgical approaches, there are some adjuvant therapies that might further stimulate healing. The aim of this systematic review is to compare outcome and effectiveness of currently available adjuvant therapies for MRONJ. METHODS: This systematic review was conducted following the PRISMA guidelines. Articles focusing on mucosal healing in patients treated with an adjuvant therapy for MRONJ were selected and analysed. Inclusion was not limited to randomized controlled trials to present a complete review of the current literature. RESULTS: A search was performed in Pubmed, Embase, Web of Science and Cochrane Central Register of Controlled Trials. Thirty articles out of 3297 were included. Laser ablation had a success of 60-95% for complete healing. The controlled trials of leukocyte- and platelet-rich-fibrine (LPRF) showed 60-100% success for the same outcome. Fluorescence guided surgery had a complete healing percentage of 85-90%. CONCLUSIONS: The results suggest that laser ablation, LPRF and fluorescence guided surgery might have a potential in improving the healing process. Interpreting the results should however be done with great care and a critical point of view, as most articles had a medium to high risk of bias. More randomized controlled trials are necessary to define the most beneficial therapy protocols. CLINICAL RELEVANCE: It seems that adjuvant surgical therapies for treating MRONJ are beneficial for mucosal healing, but there is only low scientific evidence.

In vivo quantification of mandibular bone remodeling and vascular changes in a Wistar rat model: A novel HR-MRI and micro-CT fusion technique.

PURPOSE: This study was performed to introduce an in vivo hybrid multimodality technique involving the coregistration of micro-computed tomography (micro-CT) and high-resolution magnetic resonance imaging (HR-MRI) to concomitantly visualize and quantify mineralization and vascularization at follow-up in a rat model. MATERIALS AND METHODS: Three adult female rats were randomly assigned as test subjects, with 1 rat serving as a control subject. For 20 weeks, the test rats received a weekly intravenous injection of 30 µg/kg zoledronic acid, and the control rat was administered a similar dose of normal saline. Bilateral extraction of the lower first and second molars was performed after 10 weeks. All rats were scanned once every 4 weeks with both micro-CT and HR-MRI. Micro-CT and HR-MRI images were registered and fused in the same 3-dimensional region to quantify blood flow velocity and trabecular bone thickness at T0 (baseline), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks), T16 (16 weeks), and T20 (20 weeks). Histological assessment was the gold standard with which the findings were compared. RESULTS: The histomorphometric images at T20 aligned with the HR-MRI findings, with both test and control rats demonstrating reduced trabecular bone vasculature and blood vessel density. The micro-CT findings were also consistent with the histomorphometric changes, which revealed that the test rats had thicker trabecular bone and smaller marrow spaces than the control rat. CONCLUSION: The combination of micro-CT and HR-MRI may be considered a powerful non-invasive novel technique for the longitudinal quantification of localized mineralization and vascularization.

Dog Bite Injuries in the Head and Neck Region: A 20-Year Review.

Dog bite-related wounds seem to have become a common problem, especially when they relate to the head and neck region. According to Overall and Love, up to 18 per 1,000 people sustain a dog bite every year, of whom 3 need medical attention. Approximately 1 to 2% of bite injuries require hospitalization of the victims. Most of the lacerations are found in the upper lip and the nose regions and they are classified according to severity and concomitant damage to other organs. Bite wounds are considered "dirty" wounds and are prone to infection. When dealing with bite wounds, there is always an indication for antibiotic treatment. Broad-spectrum antibiotics like amoxicillin-clavulanate and/or moxifloxacin cover most of the pathogenic flora and should be administered in every bite wound case at risk of infection. This article would like to present a medical record review: a retrospective analysis of all bite wounds sustained in the head and neck region, treated at the University Hospital of Leuven over the past 20 years. Furthermore, it provides an overview of the current literature and its standings on the treatment of dog bite injuries in the maxillofacial region. We assessed both surgical and medical treatment options, as well as primary management, which includes infection prevention strategies, closure management, and additional vaccination requirements. Secondary management or scar revision methods will be mentioned. After conducting a UZ Leuven database search using keywords such as "dog," "dog bite," "face," "head," "lip," and others, 223 patients were included. Age at the time of injury, location of the injury, treatment method used, and whether secondary infection was present or not were documented. All patients have been divided in age groups. We concluded that 21.52% was 5 years old or younger. Almost half of our patients (49.33%) were 18 years old or younger. Of all patients, 79 were hospitalized (35.43%). Primary closure was the treatment of choice. In 141 patients, the wounds were closed primarily (63.23%), resulting in only 2.24% reported secondary infections. Only one fatality was reported in our center over the course of 20 years (0.45%), a 6-year-old girl who had been attacked by her father's Rottweilers. Most patients who sustained dog bite injuries in the head and neck region seem to be children, specifically toddlers. Due to their height, it is possible they are more prone to dog bite injuries in the head and neck region. It is essential to optimize management of these injuries due to the impact they have on patients. This article provides the epidemiological data and clinical outcome of the approach at our center.

Long-term outcomes and prognosis in submandibular gland malignant tumors: A multicenter study.

OBJECTIVES/HYPOTHESIS: Submandibular gland tumors (SMGTs) are rare and characterized by heterogeneity in histologic profiles. The aim of the present study was to retrieve data on submandibular gland (SMG) malignancies and identify factors influencing survival. STUDY DESIGN: Retrospective study. METHODS: A multicenter, retrospective study on patients who underwent primary surgery for SMGTs at three referral centers was performed. RESULTS: Among 204 patients with SMGTs, 50 (24.5%) with SMG malignancies were analyzed in detail. Definitive pT status was: 21 (42%) pT1, 14 (28%) pT2, 10 (20%) pT3, and five (10%) pT4. Nodal metastases and perineural spread were diagnosed in 15 (30%) and 25 (50%) patients, respectively. High-grade lesions were identified in 32 (64%) patients. Follow-up status, available for 49 (98%) patients, was as follows: 23 (47%) patients were alive without disease, 11 (22.5%) died of disease, five (10.2%) alive with disease, and 10 (20.4%) died of other causes. Five- and 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were 66.4% and 57.1%, 76.6% and 72.1%, 69.1% and 62.4%, respectively. At univariate analysis, OS, DSS, and RFS were influenced by pT status, pN status, and perineural spread. OS and RFS were also affected by the presence of facial palsy and pain. RFS was negatively influenced by positive margins. Multivariate analysis confirmed that OS, DSS, and RFS were independently affected by perineural spread, whereas nodal involvement influenced only RFS. CONCLUSIONS: The malignancy rate of SMGTs is comparable to that reported for parotid tumors. Most patients presented with high-grade lesions. pT status, pN status, and perineural spread significantly affected prognosis. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2745-2750, 2018.

Microbial population changes in patients with medication-related osteonecrosis of the jaw treated with systemic antibiotics.

OBJECTIVE: This study aimed to investigate the bacterial population in patients with medication-related osteonecrosis of the jaw (MRONJ) after treatment with doxycycline and metronidazole. STUDY DESIGN: A total of 38 patients with MRONJ (age range 55-88, mean age 73 + 8.82 standard deviation) treated with doxycycline first and with metronidazole second were enrolled in this study. Two swabs were taken at the margin of the infected MRONJ lesion after applying pressure on the marginal mucosa, and visible pus was secreted. Real-time polymerase chain reaction was used to analyze 20 periopathogenic and commensal species and the total bacterial level. Bacterial counts were compared between antibiotic treatments and with a control group of orally healthy patients who didn't have periodontal pockets of more than 3 mm (n = 29) by means of a Mann-Whitney U test. Comparisons between the two antibiotic treatments were performed by a paired Wilcoxon signed rank test. RESULTS: The total bacterial level was significantly higher in the MRONJ patients treated with systemic antibiotics compared with the control group. However, significant lower bacterial amounts were found for 12 of the 20 investigated bacteria. We couldn't establish a significant advantage of metronidazole administration after doxycycline treatment. CONCLUSION: Our findings suggest that the total bacterial level in MRONJ patients is higher even when treated with systemic antibiotics. The significantly different bacterial amounts of the selected species suggest an alteration in the microbial population.

Incidence of osteonecrosis of the jaw in patients with bone metastases treated sequentially with bisphosphonates and denosumab.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a serious adverse event of bone resorption inhibitors (BRIs), such as bisphosphonates and denosumab. Bisphosphonates and denosumab inhibit osteoclast function through different pharmacological effects and bisphosphonates are retained in bone for several months to years. Sequential treatment with bisphosphonates and denosumab might lead to an overlapping treatment effect, due to the addition of the effect of denosumab on the residual bisphosphonate effect. Therefore, the aim of our study was to investigate if switching from denosumab to bisphosphonates is associated with a higher incidence of ONJ. METHODS: We retrospectively reviewed records of patients with solid tumors and bone metastases treated with denosumab after prior treatment with bisphosphonates at the University Hospitals Leuven (sequential group). Patients treated with denosumab or bisphosphonates alone were used as control groups. RESULTS: We identified 110 patients sequentially treated with bisphosphonates and denosumab with a median total BRI exposure of 36 months (sequential group). Median bisphosphonates exposure was 16 months and median denosumab exposure was 13 months. About 299 patients were included in the bisphosphonates control group with a median bisphosphonate exposure 19 months. About 6.7% (20/299) of patients developed ONJ. About 240 patients were included in the denosumab control group with a median denosumab exposure 17.5 months. About 10.0% of patients (24/240) developed ONJ. In the sequential group, 15.5% of patients (17/110) developed ONJ. The incidence of ONJ was 1.8% (2/110), 6.3% (6/99), 4.9% (4/82), 5.6% (3/54), and 3.4% (1/29), respectively in the first, second, third, fourth, and fifth year of BRI exposure, an ONJ-incidence similar to ONJ-incidence in the denosumab control group. In a time-to-ONJ-analysis, the curves of the sequential group and the denosumab control group were overlapping. In the sequential group, most of the ONJs occurred in the first year of denosumab exposure and in a matched control group analysis, with correction for median BRI-exposure, ONJ cases tend to occur earlier in the sequential group compared to ONJ cases in the bisphosphonates group. CONCLUSION: Cancer patients with bone metastases treated with BRIs seem to have a slightly higher risk of ONJ early after switching from bisphosphonates to denosumab compared to patients remaining on bisphosphonates. Nevertheless, based on the global ONJ-incidence, the switch from bisphosphonates to denosumab can be considered as safe as an equivalent exposure to denosumab from the start on.

A multicenter case registry study on medication-related osteonecrosis of the jaw in patients with advanced cancer.

PURPOSE: This observational case registry study was designed to describe the natural history of cancer patients with medication-related osteonecrosis of the jaw (ONJ) and evaluate the ONJ resolution rate. METHODS: Adults with a diagnosis of cancer and with a new diagnosis of ONJ were enrolled and evaluated by a dental specialist at baseline and every 3 months for 2 years and then every 6 months for 3 years until death, consent withdrawal, or loss to follow-up. The primary endpoint was the rate and time course of ONJ resolution. Secondary endpoints included frequency of incident ONJ risk factors, ONJ treatment patterns, and treatment patterns of antiresorptive agents for subsequent ONJ. RESULTS: Overall, 327 patients were enrolled; 207 (63%) were continuing on study at data cutoff. Up to 69% of evaluable patients with ONJ had resolution or improvement during the study. ONJ resolution (AAOMS ONJ staging criteria) was observed in 114 patients (35%); median (interquartile range) time from ONJ onset to resolution was 7.3 (4.5-11.4) months. Most patients (97%) had received antiresorptive medication before ONJ development, 9 patients (3%) had not; 68% had received zoledronic acid, 38% had received denosumab, and 10% had received pamidronate (56% had received bisphosphonates only, 18% had received denosumab only, and 21% had exposure to both). CONCLUSIONS: These results are consistent with those observed in clinical trials evaluating skeletal-related events in patients with advanced malignancy involving bone. Longer follow-up will provide further information on ONJ recurrence and resolution rates between medically and surgically managed patients.