Reduction of MRONJ risk after exodontia by virtue of ozone infiltration: A randomized clinical trial.

INTRODUCTION: 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. CONCLUSION: 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.

Italian position paper (SIPMO-SICMF) on medication-related osteonecrosis of the jaw (MRONJ).

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. CONCLUSION: 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.

Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

Oral health status of 916 children in Tibetan settlement (Bylakuppe, India): A cross-sectional descriptive study.

BACKGROUND: Dietary and oral hygiene habits among integrated migrant cultural minorities can vary and could impact susceptibility to caries. AIM: This study aimed to assess and compare the oral health status of Tibetan schoolchildren living in the Tibetan settlement of Bylakuppe, India, stratified by type of residence. DESIGN: A descriptive cross-sectional study was conducted among Tibetan schoolchildren attending nine schools in the Bylakuppe region. RESULTS: The study population consisted of 916 children aged 5-17: 702 (76.6%) living in secular houses (LSH) and 214 (23.4%) living in monasteries (LM). The prevalence of dental caries was 70.9%, and the mean value of decayed, missing, filled teeth for mixed and primary dentition (DMFT*; dmft) of LSH children (1.56 ± 2.34/1.74 ± 2.66) was higher than of LM ones (1.14 ± 2.34/0.83 ± 2.80; p < .001). DMFT for LM children (1.46 ± 2.04) was slightly higher than for LSH children (1.38 ± 1.96; p > .05). Among the sample, 99.1% had a good simplified Oral Hygiene Index (OHI) and LM children showed higher rates of good values (99.5% vs. 98.2% in LSH children). Most children needed preventive/routine dental treatment, whereas 16.6% needed urgent dental treatment. In 4.5% of children, oral mucosal lesions were present. CONCLUSION: This study confirms the high need for dental treatment in the children of the Tibetan settlement investigated.

Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw.

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is multifactorial and there is a substantial consensus on the role of antiresorptive drugs (ARDs), including bisphosphonates (BPs) and denosumab (Dmab), as one of the main determinants. The time exposure, cumulative dose and administration intensity of these drugs are critical parameters to be considered in the treatment of patients, as cancer patients show the highest incidence of MRONJ. BPs and Dmab have distinct mechanisms of action on bone, but they also exert different effects on immune subsets which interact with bone cells, thus contributing to the onset of MRONJ. Here, we summarized the main effects of ARDs on the different immune cell subsets, which consequently affect bone cells, particularly osteoclasts and osteoblasts. Data from animal models and MRONJ patients showed a deep interference of ARDs in modulating immune cells, even though a large part of the literature concerns the effects of BPs and there is a lack of data on Dmab, demonstrating the need to further studies.

A Reciprocal Link between Oral, Gut Microbiota during Periodontitis: The Potential Role of Probiotics in Reducing Dysbiosis-Induced Inflammation.

Human body is colonized by a florid microbial community of bacteria, archaea, fungi, protists, helminths, and viruses, known as microbiota, which co-evolves with the host and influences its health through all stages of its life. It is well known that oral microorganisms form highly structurally and functionally organized multi-species biofilms and establish a network of complex mutual inter-species interactions having a primary function in synergy, signaling, or antagonism. This ecological model allows the microorganisms to increase their resistance to antimicrobial agents and settle a balanced microbes-host symbiotic relationship that ensures oral and global health status in humans. The host-associated microbiome is an important factor in human health and disease. Therefore, to develop novel diagnostic, therapeutic, and preventive strategies, microbiome's functions and the reciprocal interactions every microbiome entertains with other microbial communities in the human body are being investigated. This review provides an analysis of the literature about the close connection between the two largest microbial communities in humans: the oral and the gut microbiomes. Furthermore, it focuses on how the alteration of their microbial and functional characteristics can lead to and reciprocally influence the onset of both oral and intestinal microbiome-associated illness, along with the potential role of probiotics in ameliorating inflammation and microbial dysbiosis.

MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series.

BACKGROUND: Cancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ. METHODS: This multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients' data were retrospectively collected from the clinical charts of seven recruiting Italian centres. RESULTS: MRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandible (73.3%). The mean duration of BMAs therapy at MRONJ presentation was 34.9 months. The more frequent BMAs was denosumab (53.3%). Ten patients (66.7%) showed the following local risk factors associated to MRONJ development: periodontal disease (PD) in three cases (20%) and the remaining six (40%) have undergone PD-related tooth extractions. One patient presented an implant presence-triggered MRONJ (6.7%). In five patients (33.3%) no local risk factors were observed. CONCLUSIONS: This is the first case series that investigated BC patients under BMAs for CTIBL prevention suffering from MRONJ. These patients seem to have similar probabilities of developing MRONJ as osteo-metabolic ones. Breast cancer patients under BMAs for CTIBL prevention need a regular prevention program for MRONJ, since they may develop bone metastases and be treated with higher doses of BMAs, potentially leading to a high-risk of MRONJ.

The preventive care of medication-related osteonecrosis of the jaw (MRONJ): a position paper by Italian experts for dental hygienists.

PURPOSE: The prevention and early diagnosis of medication-related osteonecrosis of the jaw (MRONJ) is fundamental to reducing the incidence and progression of MRONJ. Many in the field believe that dental hygienists should play an integral role in primary and secondary MRONJ prevention. However, to date, very few publications in the literature have proposed standardised MRONJ protocols, which are dedicated to dental hygienists. The aim of this study was to provide guidance to the health care providers managing MRONJ. METHODS: The expert opinion in this study was developed by dental hygienists from the main Italian technical-scientific associations (Italian Dental Hygienists Association, AIDI and National Union of Dental Hygienists, UNID) and authors of the latest Italian recommendations regarding MRONJ from the field of dentistry and maxillofacial surgery. RESULTS: The oral care protocol outlined in this position paper is focused on the role of dental hygienist in patients at risk or affected by MRONJ, and it regards 3 main issues: primary prevention, secondary prevention and supporting the treatment of MRONJ. Each issue contains easy-to-apply indications and procedures, as described by the authors, regarding the role of the dental hygienist. CONCLUSION: Referring to the main issues under consideration (primary prevention, secondary prevention and the treatment of MRONJ), a clinical examination of periodontal tissue is critical in preventing MRONJ. It is the opinion of the authors of this study that the application of a periodontal screening score is fundamental in defining personalised strategies for patients at risk of MRONJ. By means of these basic procedures, a protocol for assisting the health care provider and the presentation of a practical approach for patients at risk or affected by MRONJ are described in this study.

Peri-implantitis-like medication-related osteonecrosis of the jaw: Clinical considerations and histological evaluation with confocal laser scanning microscope.

OBJECTIVE: In the recent years, an increasing number of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) have been reported in literature, both in oncologic and osteoporotic patients. The aim of this study is to describe 19 cases of patients previously diagnosed as affected by peri-implantitis, who were treated for PI-MRONJ, with consideration on clinical and histopathological features. MATERIALS AND METHODS: Patients included were affected by postmenopausal osteoporosis and were administered with different antiresorptive drugs. Due to the presence of clinical and radiological signs of peri-implantitis not healed after non-surgical periodontal treatment, they were referred to the Complex Operating Unit of Odontostomatology of the University of Bari. Then, after a drug holiday of at least 3 months and cycles of antibiotics, and after other cycles of periodontal treatment, patients underwent the surgical removal of implant fixtures and surrounding bone. RESULTS: Although the previous diagnosis of peri-implantitis, the histopathological analysis with both conventional and confocal laser scanner microscopy confirmed the diagnosis of peri-implantitis-like MRONJ. CONCLUSION: Peri-implantitis not healed after conventional treatment in patients at risk on MRONJ occurrence should be considered as peri-implantitis-like PI-MRONJ and treated as required in order to get complete healing of the pathological condition, thus avoiding delay in the diagnosis.

Protein Cargo of Salivary Small Extracellular Vesicles as Potential Functional Signature of Oral Squamous Cell Carcinoma.

The early diagnosis of oral squamous cell carcinoma (OSCC) is still an investigative challenge. Saliva has been proposed as an ideal diagnostic medium for biomarker detection by mean of liquid biopsy technique. The aim of this pilot study was to apply proteomic and bioinformatic strategies to determine the potential use of saliva small extracellular vesicles (S/SEVs) as a potential tumor biomarker source. Among the twenty-three enrolled patients, 5 were free from diseases (OSCC_FREE), 6 were with OSCC without lymph node metastasis (OSCC_NLNM), and 12 were with OSCC and lymph node metastasis (OSCC_LNM). The S/SEVs from patients of each group were pooled and properly characterized before performing their quantitative proteome comparison based on the SWATH_MS (Sequential Window Acquisition of all Theoretical Mass Spectra) method. The analysis resulted in quantitative information for 365 proteins differentially characterizing the S/SEVs of analyzed clinical conditions. Bioinformatic analysis of the proteomic data highlighted that each S/SEV group was associated with a specific cluster of enriched functional network terms. Our results highlighted that protein cargo of salivary small extracellular vesicles defines a functional signature, thus having potential value as novel predict biomarkers for OSCC.

Leucocyte- and Platelet-Rich Fibrin Block: Its Use for the Treatment of a Large Cyst with Implant-Based Rehabilitation.

The management of critical-size bone defects is still demanding. Recently, autologous platelet concentrates in combination with bone substitute have been applied and reported in a few studies. Our aim is to report the healing of a critical-size alveolar bone defect treated with a new bone regeneration technique by means of L-PRF and L-PRF blocks. A 45-year-old woman presented a large cystic lesion; the extraction of three teeth, a cyst removal procedure, and bone regeneration procedures with L-PRF and L-PRF blocks were planned. The L-PRF block was prepared by mixing a bone substitute with a piece of L-PRF membrane and liquid fibrinogen. Additionally, after bone healing an implant-based rehabilitation was optimally performed. On the basis of the positive results, in terms of bone healing and tissue regeneration in a large bone defect, the application of L-PRF and L-PRF blocks, in agreement with the scarce literature, is suggested as a feasible procedure in selected cases.

Gingival displacement using diode laser or retraction cords: A comparative clinical study.

PURPOSE: To compare two systems used for conditioning the gingival sulcus and exposing the finish line before the final impression for a fixed denture: retraction cords and diode laser. METHODS: All subjects participating in the study had healthy gingival and periodontal status before intervention for fixed prosthesis. 74 abutments for complete crown restoration were randomly divided into two groups for displacing the gingival sulcus before the final impression: gingival retraction cords (RC) and diode laser (DL). The height of the clinical crowns was measured by a blinded examiner in three points of the buccal surface (mesial, midline and distal) at four different times: after tooth preparation (T0), 15 days after tooth preparation, before exposing the finish line with RC or with DL (T1), 10 minutes after exposing the finish line (T2), and 15 days after the final impression was taken (T3). The amount of gingival retraction produced (ΔT2-T1) and restoration to baseline (ΔT3-T1) were calculated. Ease of technique and patient comfort were evaluated through the Visual Analog Scale. The time required to carry out the technique and bleeding during and after the conditioning procedure were also evaluated. RESULTS: There was no difference between the two techniques with regard to the height differences: ΔT2-T1 was 0.65±0.33 for RC and 0.66#177;0.43 for the DL (P= 0.966), while ΔT3-T1 was 0.03#177;0.27 for RC and 0.02#177;0.46 for DL (P= 0.286). DL required less time, was easier for the operator and more comfortable than RC for the patient (all P<0.001). CLINICAL SIGNIFICANCE: The amount of gingival retraction and restoration to baseline resulting from use of gingival retraction cords or diode laser technique is similar, but diode laser required less time, was simpler for the operator and was more comfortable to the patient than retraction cords.

Polymorphous Adenocarcinoma: A Systematic Review of the Literature and Presentation of Two Cases in a Less-Considered Anatomical Site.

BACKGROUND: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two cases of patients affected by PAC in an infrequently considered anatomical site. METHODS: According to PRISMA guidelines, a systematic review search was conducted on PubMed, Scopus, and Web of Science. Observational studies conducted on patients with a histological diagnosis of PAC were selected and analysed. Furthermore, two cases of patients with PAC affecting the buccal mucosa were reported. RESULTS: Twenty-nine studies were included, and 143 patients affected by PAC were analysed (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years). The palate was the most affected site (99/143, 69.2%), followed by the buccal mucosa (12/143, 8.4%). Moreover, we report two cases of patients with PAC affecting the buccal mucosa (one male and one female, with a mean age of 70.5 ± 2.5 years). CONCLUSIONS: The present study underscores the importance of considering the buccal mucosa as a possible location of minor salivary gland tumours; although it is a less-considered affliction, it is not uncommon.

Ranula: Modified Micro-Marsupialization: Case Report and Review of Literature.

Introduction: Ranula is a limited mucus retention on the floor of mouth. Due to the young age of patients, over the years, attempts were made to find minimally invasive and effective surgical techniques. To date, however, there is still no gold standard. The modified micro-marsupialization is an effective and minimally invasive technique, with minimal risk of relapse, although there are very few reports about it. Case Report: A 12-year-old male presented to our ENT Clinic with a rounded swelling with regular and defined margins, measuring 4x3 cm, soft and painless, non-compressible and bluish. Clinical diagnosis of ranula was made and a modified micro-marsupialization was performed: eight interrupted sutures using silk 3-0 were placed perpendicularly to the major axis of the lesion, from one side of the lesion to the other, without reaching the underlying tissue. No sutures were lost during follow-up, no complications occurred. Complete healing was reached after removing sutures on the 30th postoperative day. At 6 months control no relapse was observed. Conclusion: Modified micro-marsupialization is strongly indicated and recommended, especially in pediatric patient, due to its low invasiveness and its very low relapse rate. The poor case history found in the literature is probably an indication of the lack of knowledge of modified micro-marsupialization which, in our opinion, could be considered the gold standard.

Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents.

Pain is the most common symptom that dentists are confronted with, whether acute (pulpitis, acute periodontitis, post-surgery, etc.) or chronic diseases, such as periodontitis, muscle pain, temporomandibular joint (TMJ) disorders, burning mouth syndrome (BMS), oral lichen planus (OLP) and others. The success of therapy depends on the reduction in and management of pain through specific drugs, hence the need to analyze new pain medications with specific activity, which are suitable for long-term use, with a low risk of side effects and interactions with other drugs, and capable of leading to a reduction in orofacial pain. Palmitoylethanolamide (PEA) is a bioactive lipid mediator, which is synthesized in all tissues of the body as a protective pro-homeostatic response to tissue damage and has aroused considerable interest in the dental field due to its anti-inflammatory, analgesic, antimicrobial, antipyretic, antiepileptic, immunomodulatory and neuroprotective activities. It has been observed that PEA could play a role in the management of the pain of orofacial origin, including BMS, OLP, periodontal disease, tongue a la carte and temporomandibular disorders (TMDs), as well as in the treatment of postoperative pain. However, actual clinical data on the use of PEA in the clinical management of patients with orofacial pain are still lacking. Therefore, the main objective of the present study is to provide an overview of orofacial pain in its many manifestations and an updated analysis of the molecular pain-relieving and anti-inflammatory properties of PEA to understand its beneficial effects in the management of patients with orofacial pain, both neuropathic and nociceptive in nature. The aim is also to direct research toward the testing and use of other natural agents that have already been shown to have anti-inflammatory, antioxidant and pain-relieving actions and could offer important support in the treatment of orofacial pain.

No Clear Clustering Dysbiosis from Salivary Microbiota Analysis by Long Sequencing Reads in Patients Affected by Oral Squamous Cell Carcinoma: A Single Center Study.

BACKGROUND: Advancements in DNA sequencing technology have facilitated the assessment of the connection between the oral microbiome and various diseases. The aim of the present study was to investigate the salivary microbiota composition employing for the first time in the literature the Oxford Nanopore Technology in patients affected by oral squamous cell carcinoma (OSCC). METHODS: Unstimulated saliva samples of 31 patients were collected (24 OSCC patients and 7 controls). DNA was extracted using the QIAamp DNA Blood Kit and metagenomic long sequencing reads were performed using the MinION device. RESULTS: In the OSCC group, 13 were males and 11 were females, with a mean age of 65.5 ± 13.9 years; in the control group, 5 were males and 2 were females, with a mean age of 51.4 ± 19.2 years. The border of the tongue was the most affected OSCC site. The microorganisms predominantly detected in OSCC patients were Prevotella, Chlamydia, Tissierellia, Calothrix, Leotiomycetes, Firmicutes and Zetaproteobacteria. CONCLUSIONS: This study confirmed the predominance of periodontopathic bacteria in the salivary microbiome in the OSCC group. If a direct correlation between oral dysbiosis and OSCC onset was proven, it could lead to new prevention strategies and early diagnostic tools.

Oral Secondary Syphilis in an HIV-Positive Transgender Patient: A Case Report and Review of the Literature.

BACKGROUND: Syphilis is a worldwide sexually transmitted infection caused by Treponema pallidum. In most cases, the oral manifestations of syphilis infection are associated with cutaneous involvement. However, the present case report is noteworthy since the oral lesions are the sole clinical sign in an HIV-positive transgender patient. CASE PRESENTATIONS: We reported an uncommon case of secondary syphilis in a 37-year-old seropositive transgender male, whose diagnostic suspect was based only on oral mucosal lesions. The patient was referred to the Oral Medicine Unit for the presence of multiple undiagnosed painful oral lesions. The intraoral examination revealed the presence of white and red plaques on the right and the left buccal mucosa and several painful lesions localized on the upper and lower labial mucosa. No cutaneous lesions were observed. Considering the sexual history of the patient and clinical findings, secondary syphilis infection was suspected. The serologic analysis was conducted, and the diagnosis of syphilis was confirmed. Moreover, to exclude the presence of oral epithelial dysplasia or malignant disease, an incisional biopsy was performed. DISCUSSION: Compared to the literature data, oral lesions as lone signs of secondary syphilis infection are uncommon, especially in HIV-positive patients. Syphilis and HIV coinfection create a concerning situation as they interact synergistically, leading to an increased risk of transmission and faster disease progression. CONCLUSIONS: This case report emphasizes the importance of considering syphilis as a diagnostic possibility, even when oral lesions are the only clinical manifestations, especially in HIV-positive patients. Comprehensive evaluation, including a detailed sexual history and careful oral examination, is essential for accurate diagnosis and appropriate management in such cases.