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UNASSIGNED: There is a scarcity of evidence concerning the use of a prognostic instrument for predicting normal healing, delayed healing, and medication-related osteonecrosis of the jaw (MRONJ) occurrence following tooth extraction in medically compromised patients. The present study aimed to predict healing outcomes following tooth extraction in medically compromised patients using an Adapted-University of Connecticut osteonecrosis numerical scale (A-UCONNS).
UNASSIGNED: The digital medical records of medically compromised patients were reviewed, who underwent tooth extraction. The A-UCONNS parameters included the initial pathological condition, dental procedures, comorbidities (smoking habits, type and duration of medication, and type of intervention), and administered antiresorptive (AR) medications. Each parameter was assigned a different weight, and the scores were then accumulated and classified into three categories: minimal risk (less than 10), moderate risk (10-15), and significant risk (16 or more). The patient\'s healing status was categorized as normal healing, delayed healing, or MRONJ.
UNASSIGNED: A total of 353 male patients (mean age: 67.4 years) were recruited from a pool of 3977 patients, where 12.46% of patients had delayed wound healing, and 18.69% developed MRONJ. The median A-UCONNS scores for MRONJ were higher based on initial pathology, comorbidity, and AR drugs compared to normal or delayed healing. In addition, a significant relationship existed between A-UCONNS and healing outcomes (p < 0.05), with a unit increase in A-UCONNS associated with 1.347 times higher odds of experiencing MRONJ compared to normal healing. In contrast, a low score was linked to an increased likelihood of normal wound healing.
UNASSIGNED: The A-UCONNS could act as a promising tool for predicting wound healing outcomes. It can provide clinicians the ability to pinpoint patients at high risk and allow tailoring of patient-specific strategies for improving healing outcomes following tooth extraction.

BACKGROUND: Exodontia is commonly considered as a risk factor for the development of medication-related osteonecrosis of the jaw (MRONJ) in individuals exposed to bone modifying agents. This study was aimed at assessing the efficiency and safety of a gaseous oxygen-ozone mixture as an adjuvant to a standard exodontia to reduce the risk of MRONJ development.
METHODS: A randomized, open-label, phase II, single-center clinical trial involving 117 patients at risk of MRONJ was conducted. The study protocol tested injections of an oxygen-ozone mixture in the post-extraction site. Participants were randomly assigned to two groups: oxygen-ozone therapy, and standard tooth extraction protocol. Post-extraction wound healing was assessed using the Inflammatory Proliferative Remodeling (IPR) Wound Healing Scale.
RESULTS: The oxygen-ozone therapy group exhibited a significant improvement in wound healing post-extraction during the inflammatory and proliferative phases, as indicated by the IPR scale scores at 3-5 days (p = 0.006) and 14 days (p < 0.001) respectively.
CONCLUSIONS: Oxygen-ozone therapy shows promise in improving post-extraction healing in patients at risk of MRONJ. Future studies with larger sample sizes and multicenter collaborations are recommended to confirm the validity of these findings and explore the long-term efficacy of ozone therapy.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse illness linked to antiresorptive therapies (ART), for which there is no therapeutic gold standard. Many factors can influence MRONJ evolution such as cancer type, treatment, comorbidities, and accumulated dose of ART. The aim of this study was to determine the influencing factors of MRONJ treatments success.
METHODS: This retrospective study focused on patients treated for MRONJ in a French tertiary centre. Non-operative therapy was always applied, ART were suspended if appropriate, and surgery (MRONJ removal and musculo-mucosal flap reconstruction) was performed in the absence of contraindication. The evaluation criteria were bone and mucosal healing 3 months after surgery.
RESULTS: 81 MRONJ were included; medical treatment alone was administered to 26 % while the remaining 74 % received additional surgery. Therapeutic success reached 86.7 % (52/60) for surgery compared to 42.9 % (9/21) for medical treatment alone (p < 0.001). Age (OR=1.08, p = 0.014) and the absence of infection (OR=5.32, p = 0.042) were in favour of success, while medical treatment alone (OR=0.03, p < 0.001) was highly unfavourable.
CONCLUSIONS: MRONJ healing is influenced by age, non-infectious stages, and surgery. Additional surgery in MRONJ treatment should be advised if the health of the patient permits.

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of \"Osteonecrosis of jaw\" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.

The aim of this study was to investigate the jawbone concentration of clindamycin (CLI) in patients with an osteonecrosis of the jaw (ONJ). Patients with medication-related ONJ (MRONJ) and osteoradionecrosis (ORN) with an antibiotic treatment with CLI were included. Plasma, vital and necrotic bone samples were collected. Plasma and jawbone samples were analyzed by liquid chromatography-tandem mass spectrometry. Patients with MRONJ exhibited a mean plasma CLI concentration of 9.6 μg/mL (SD ± 3.6 μg/mL) and mean concentrations of 2.3 μg/g CLI (SD ± 1.4 μg/g) and 2.1 μg/g CLI (SD ± 2.4 μg/g) in vital and necrotic bone samples, without statistical significance (p = 0.79). In patients with ORN, mean concentration in plasma was 12.0 μg/mL (SD ± 2.6 μg/mL), in vital bone 2.1 μg/g (SD ± 1.5 μg/g), and in necrotic bone 1.7 μg/g (SD ± 1.2 μg/g). Vital and necrotic bone concentrations did not differ significantly (p = 0.88). The results demonstrate that CLI concentrations are considerably lower than in plasma, but sufficient for most bacteria present in ONJ. Within the limitations of the study, it seems that CLI is a relevant alternative to other antibiotics in the treatment of ONJ because it reaches adequate concentrations in jawbone.

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable adverse event. Dental implants are one of the triggering factors of MRONJ, and implant therapy with low MRONJ risk is required. This study aimed to investigate a rat model of MRONJ induced by extraoral placement of titanium materials and the use of mesenchymal stromal cell (MSCs) sheets to prevent MRONJ. Eight-week-old male rats were administered zoledronate and dexamethasone thrice weekly until killing. A week after drug initiation, a titanium screw and a plate were placed on the left buccal side of the mandible. Allogeneic bone marrow-derived MSC sheets were co-grafted with the titanium plates in the MSC sheet ( +) group. Six weeks after titanium placement, the rats were killed, and their excised mandibular bones were subjected to micro-computed tomography (CT) analysis. Histological analysis was performed after the titanium implants were removed. Empty lacunae visualized on hematoxylin and eosin staining were used as evidence of bone necrosis. Bone necrosis was reduced in the MSC sheet ( +) group. Tartrate-resistant acid phosphatase (TRAP) staining revealed a decreased number of TRAP-positive cells in areas with a large number of empty lacunae in the MSC sheet (-) group. Micro-CT analyses demonstrated that the bone volume fraction (BV/TV) was not significantly different between the MSC sheet (-) and ( +) groups. We conclude that MRONJ can be triggered by a titanium placement in rats, and grafting of allogeneic MSC sheets has the potential to prevent MRONJ.

UNASSIGNED: The aim of this retrospective study was to identify the clinical, radiological, and histological characteristics of patients diagnosed with osteonecrosis of the jaw (ONJ) and treated at the Oral and Maxillo-Facial Surgery Clinic of the Emergency Clinical County Hospital of Targu Mures between 2017 and 2022. The study aimed to analyze correlations between patient characteristics, particularly their history of bone modifying agent use or local radiotherapy during cancer treatment, in order to identify specific patient profiles that could aid in evaluating treatment response and guide individualized treatment strategies.
UNASSIGNED: Fifty-two patients diagnosed with ONJ were included in the study. The patients were divided into two groups based on their medical history: the bone modifying agent use group and the radiotherapy group. Clinical, radiological, and histological data were collected and analyzed. Statistical analysis, including p-values, was performed to compare patient characteristics between the two groups.
UNASSIGNED: Patients in the radiotherapy group were significantly older than those in the bone modifying agent use group (66 years vs. 56.9 years, p=0.001). There was a higher proportion of males in the radiotherapy group compared to the bone modifying agent use group (90% vs. 22%, p<0.001). Jaw involvement was more prevalent in the radiotherapy group compared to the bone modifying agent use group (95% vs. 66%, p=0.018). Histological analysis showed a similar frequency of Actinomyces species in both groups (50% vs. 34%, p=0.264).
UNASSIGNED: The findings of this study suggest the existence of two distinct patient profiles based on their treatment history (bone modifying agent use vs. radiotherapy) in ONJ. Patients in the radiotherapy group were older, predominantly male, and exhibited a higher prevalence of jaw involvement. Histological analysis revealed no significant differences in Actinomyces species frequency between the two groups. These distinct patient profiles may indicate different responses to treatment, emphasizing the need for individualized treatment strategies tailored to specific patient characteristics. Further research is warranted to validate these findings and develop personalized approaches for managing ONJ.

Osteonecrosis of the jaw is the progressive loss and destruction of bone affecting the maxilla or mandible in patients treated with antiresorptive and antiangiogenic agents without receiving prior radiation therapy. The pathogenesis involves the inflammatory pathway of receptor activator of nuclear factor NF-kB ligand and the macrophage colony-stimulating factor, essential for osteoclast precursors survival and proliferation and acting through its receptor c-Fms. Evidence has shown the role of non-coding RNAs in the pathogenesis of osteonecrosis of the jaw and this finding might be useful in diagnosis since these small RNAs could be considered as biomarkers of apoptotic activity in bone. Interestingly, it has been proved that miR-29 and miR-31-5p, acting on specific targets such as CALCR and RhoA, promote programmed-cell death and consequently the necrosis of bone tissue. Specific long non-coding RNAs, instead, have been detected both at reduced levels in patients with multiple myeloma and osteonecrosis, and associated with suppression of osteoblast differentiation, with consequences in the progression of mandible lesions. Among non-coding genic material, circular RNAs have the capability to modify the expression of specific mRNAs responsible for the inhibition of bisphosphonates activity on osteoclastogenesis.

OBJECTIVE: This paper aims to describe the 2023 update position paper on MRONJ developed by the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Maxillofacial Surgery (SICMF).
METHODS: This is the second update following the 2013 and 2020 Italian position papers by the Expert panel, which is a representation of the two scientific societies (SIPMO and SICMF). The paper is based on an extensive analysis of the available literature from January 2003 to February 2020, and the subsequent review of literature conducted between March 2020 and December 2022 to include all new relevant published papers to confirm or modify the previous set of recommendations.
RESULTS: This position paper highlights the main issues of MRONJ on risk estimates, disease definition, diagnostic pathway, individual risk assessment, and the fundamental role of imaging in the diagnosis, classification, and management of MRONJ.
CONCLUSIONS: The Expert Panel confirmed the MRONJ definition, the diagnostic work-up, the clinical-radiological staging system and the prophylactic drug holiday, as recognized by SIPMO-SICMF; while, it presented novel indications regarding the categories at risk of MRONJ, the prevention strategies, and the treatment strategies associated with the therapeutic drug holiday.