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In recent scientific literature, oral infections and systemic manifestations, or correlations between oral health and systemic diseases are a topic of discussion. Porphyromonas gingivalis is one of the bacteria implicated in the biofilm formation of bacterial plaque, and plays an important role in the progression of periodontal disease. In this systematic review authors have evaluated the literature of the last 10 years on P. gingivalis and all the systemic implications proven. This study therefore evaluates all the districts of the organism in which this bacterium may have implications. From the results it emerges that P. gingivalis has implications in the onset of different systemic pathologies, including rheumatoid arthritis, cardiovascular pathologies, and neurodegenerative pathologies. Surely, understanding the mechanisms of diffusion of this bacterium, it would be possible to prevent a series of pathologies. Thus, putting the dentist clinician at the center of prevention for these diseases.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is a potentially painful and debilitating condition that can considerably affect the quality of life of patients. Furthermore, even if its epidemiology and pathogenesis have still not been fully clarified, several risk factors related to MRONJ have been recognized in prevention protocols. Three main risk factors are as follows: (i) the type of ONJ-related medications: antiresorptive (e.g., Bisphosphonates, Denosumab) and antiangiogenic drugs (e.g., Bevacizumab, Sunitinib); (ii) the category of patient at MRONJ risk: cancer versus non-cancer patient; (iii) the typologies and timing of dental treatments (e.g., before, during, or after the drug administration). The aim of this paper is to describe the new paradigm by the Italian Society of Oral Pathology and Medicine (SIPMO) on preventive dental management in patients at risk of MRONJ, prior to and during/after the administration of the aforementioned ONJ-related drugs. In reducing the risk of MRONJ, dentists and oral hygienists are key figures in applying a correct protocol of primary prevention for pre-treatment and in-treatment patients. However, the necessity of a multidisciplinary standardized approach, with a sustained dialogue among specialists involved, should be always adopted in order to improve the efficacy of preventive strategies and to ameliorate the patient’s quality of life.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Background Chronic periodontal disease is an infectious disease consisting of prolonged inflammation of the supporting tooth tissue and resulting in bone loss. Guided bone regeneration procedures have become common and safe treatments in dentistry, and in this context dental stem cells would represent the ideal solution as autologous cells. In this study, we verified the ability of dental pulp mesenchymal stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) harvested from periodontally affected teeth to produce new mineralized bone tissue in vitro, and compared this to cells from healthy teeth. Methods To characterize DPSCs and GMSCs, we assessed colony-forming assay, immunophenotyping, mesenchymal/stem cell phenotyping, stem gene profiling by means of flow cytometry, and quantitative polymerase chain reaction (qPCR). The effects of proinflammatory cytokines on mesenchymal stem cell (MSC) proliferation and differentiation potential were investigated. We also observed participation of several heat shock proteins (HSPs) and actin-depolymerizing factors (ADFs) during osteogenic differentiation. Results DPSCs and GMSCs were successfully isolated both from periodontally affected dental tissue and controls. Periodontally affected dental MSCs proliferated faster, and the inflamed environment did not affect MSC marker expressions. The calcium deposition was higher in periodontally affected MSCs than in the control group. Proinflammatory cytokines activate a cytoskeleton remodeling, interacting with HSPs including HSP90 and HSPA9, thioredoxin-1, and ADFs such as as profilin-1, cofilin-1, and vinculin that probably mediate the increased acquisition in the inflamed environment. Conclusions Our findings provide evidence that periodontally affected dental tissue (both pulp and gingiva) can be used as a source of MSCs with intact stem cell properties. Moreover, we demonstrated that the osteogenic capability of DPSCs and GMSCs in the test group was not only preserved but increased by the overexpression of several proinflammatory cytokine-dependent chaperones and stress response proteins.

The natural polyphenol Resveratrol (RSV) claims numerous positive effects on health due to the well documented biological effects demonstrating its potential as a disease-preventing agent and as adjuvant for treatment of a wide variety of chronic diseases. Since several studies, both in vitro and in vivo, have highlighted the protective bone aptitude of RSV both as promoter of osteoblasts’ proliferation and antagonist of osteoclasts’ differentiation, they could be interesting in view of applications in the field of dentistry and maxillofacial surgery. This review has brought together experimental findings on the use of RSV in the regeneration of bone tissue comprising also its application associated with scaffolds and non-transfusional hemocomponents.

Denosumab is associated with the development of medication-related osteonecrosis of the jaw (MRONJ), an uncommon but severe oral side effect with a higher prevalence in metastatic cancer patients than in patients with metabolic bone fragility. Although several oral triggers can initiate MRONJ, invasive oral treatments and tooth extraction still remain the most common precipitating event. In general, tooth extraction and oral surgery should be avoided in patients at increased risk of MRONJ, while extraction of non-restorable teeth should be performed based on specific risk reduction protocols to eliminate dental/periodontal infections, still protecting from MRONJ onset. Based on the different pharmacological activity of denosumab and nitrogen-containing bisphosphonates, it is likely that the MRONJ risk profile of patients with osteoporosis could somewhat vary. We hypothesize the chance to maximize the pharmacokinetic of denosumab 60 mg (Prolia®) and identify a time interval in which invasive oral treatments can ideally take place without restrictions in patients with metabolic bone fragility, We propose that dental surgery (e.g. tooth extraction) may be safely performed without additional intra or peri-operative procedures in osteoporosis patients using denosumab provided that careful case selection, adequate communication among specialists, planning of a delayed dosing window (1-month deferral) and rigorous postoperative follow-up are granted. Graphical abstract

Field cancerization (FC) is a well-documented phenomenon in oral squamous cell carcinoma (OSCC), typically reported in patients with known risk habits such as tobacco and alcohol use. To date, limited evidence exists regarding FC in individuals without traditional carcinogenic exposures, as well as in those associated with chronic mechanical trauma. The study aims to report a case series of FC in patients without well-known risk habits observed in the last two years. This study is a retrospective cohort study conducted at the Unit of Oral Medicine \"V. Margiotta\" of the University Hospital \"Paolo Giaccone\" in Palermo (Italy). Between January 2023 and February 2025, a total of 64 patients affected by OSCC were observed. All cases were histologically confirmed through biopsy. For the present study, we focused specifically on the subgroup of patients who developed synchronous and/or metachronous lesions during this period. A retrospective analysis was conducted on eight female patients (mean age: 75.5 ± 10.3 years) diagnosed with multifocal OSCC. Three patients presented with synchronous lesions, three with metachronous lesions, and two developed both types over time. Six patients (75%) were denture wearers. This study highlights the relevance of FC in elderly OSCC patients with no history of traditional carcinogenic exposures, except for the high prevalence of denture use, which, however, cannot be considered a clear causal factor. Long-term clinical and radiological surveillance is essential for early detection of multifocal lesions, thereby improving prognosis and patient quality of life.

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.

Medication-related osteonecrosis of the Jaw (MRONJ) is an adverse drug reaction that affects the mandible and maxilla of patients exposed to BMA and AA therapies, causing the progressive destruction and death of bone. To date, oral health preventive measures remain the most effective strategy to reduce MRONJ incidence, and, in this sense, the major goal is to diagnose, treat, and eradicate any oral diseases that could compromise oral health. The present systematic review aims to investigate the awareness of MRONJ among patients assuming BMAs. A systematic literature search was performed, selecting studies that concern the awareness of patients of the risk of MRONJ. Six studies were included in this review. In total, 483 patients were evaluated. Of the 483 included patients, 391 were not aware of the possibility of MRONJ onset (391/483, 81%) and 92 were aware of it (92/483, 19%). The problem of patient's lack of awareness with respect to MRONJ risk presents different layers of complexity (\"what?\", \"who?\", \"where?\", \"when?\" and \"why?\"). Among its causal factors, there are an inadequate level of communication with patients and the lack of collaboration between healthcare professionals, which is related to an individualistic view of liability and deontological duties. MRONJ is a drug adverse reaction that can greatly affect the quality of life of patients if not promptly diagnosed and treated. Therefore, patients must be fully aware of the risks of adverse and the importance of preventive measures, which imply effective and exhaustive communication by each member of the multidisciplinary team. Effective teamwork and collaborative care should be promoted to positively impact patients' awareness.

Background: Medication-Related Osteonecrosis of the Jaw (MRONJ) is an adverse drug reaction mainly associated to bone modifying agents (BMAs). Breast cancer (BC) is the most frequent cancer worldwide. Its therapy can cause cancer treatment-induced bone loss (CTIBL), commonly treated with BMAs. The aims of this retrospective study are: to describe characteristics of BC patients under BMAs for CTIBL; to record any switch to high-dose BMAs; to assess MRONJ onset and to identify any factors associated with it. Patients: Authors included patients referred for MRONJ prevention to the Unit of Oral Medicine (University Hospital of Palermo). Results: Fourteen female BC patients under low-dose BMAs for CTIBL were eligible (mean age 66.6 years). Four patients switched to high-dose BMAs for bone metastases. In two of the four, MRONJ developed: one case, in the mandible (risedronate for 48 months then Xgeva® for 60 months); the other case, in the maxilla (Prolia® for 20 months then zoledronate for 16 months). Conclusion: It can be theorized that BC patients under BMAs for CTIBL are likely to have MRONJ risk similar to osteo-metabolic patients. These patients need more careful monitoring of oral health since they may switch, for preventing or treating bone metastases, to heavier BMAs therapy, thus increasing their risk of MRONJ.