Osteonecrosis is a debilitating condition characterized by the loss of blood supply to the bones, leading to bone death. This condition can impact various bones, including the jaw, which significantly affects patients\' quality of life by causing difficulties in swallowing, feeding, chewing, and speaking, along with swollen, painful mucous membranes and chronic sinusitis. Osteonecrosis can arise due to treatment with antiresorptive drugs. However, there is a growing number of reports of osteonecrosis following novel targeted anti-cancer treatments, such as tyrosine kinase inhibitors (TKIs) and biological therapies. The pathogenesis of osteonecrosis is linked to the side effects of the antiangiogenic mechanisms of these medications, leading to a disrupted blood flow. Our review aims to examine recent insights into osteonecrosis triggered by new anti-cancer drugs. Most reports focus on the osteonecrosis of the jaw (ONJ); however, we discovered that some authors have described cases of osteonecrosis affecting the femoral head or elbow following novel anti-cancer treatments. Prevention is a key component in managing osteonecrosis. Therefore, a comprehensive risk assessment should always be performed before and during anti-cancer therapy.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon complication of antiresorptive therapy (ART) in patients receiving higher and more frequent doses of osteoclast inhibitors. The jaws are the most common site, as they have high bone turnover. The oral structures are exposed to various types of stresses, like mastication and dental diseases, which lead to microtrauma and increased bone remodeling. The hallmark feature of MRONJ is the area of exposed, necrotic, nonhealing, asymptomatic bone for more than eight weeks. Objective signs are pain in the jaw and oral cavity, loose teeth, gingival swelling, ulceration, soft tissue infection, and paresthesia in the trigeminal nerve branches\' territory. Clinically, the MRONJ has been defined in four stages, from stage 0 to stage 3. Close coordination between the dentist and oncologist is critical for optimal treatment. Conservative management should be preferred over surgical management. There is significant underreporting and misdiagnosis of MRONJ cases in regular clinical practice. There needs to be more awareness among treating physicians about this sporadic complication of bisphosphonate therapy. This narrative review has given a detailed insight into the subject, starting with etiology, pathogenesis, incidence, clinical presentation, workup, staging, and various management strategies. The review article focuses mainly on practical aspects of MRONJ, which every clinician dealing with the disease must know. With a better awareness of this potential complication, healthcare practitioners dealing with at-risk patients can better diagnose, prevent, address, and provide necessary care.

OBJECTIVE: To review the available prospective literature on hyperbaric oxygen (HBO) therapy for periodontal conditions.
METHODS: A comprehensive electronic and manual search was performed to identify clinical studies on adult patients who underwent hyperbaric oxygen therapy for periodontal treatments. A systematic literature search was conducted in PubMed, Cochrane, and Dentistry Oral Sciences Source databases.
RESULTS: Fourteen articles were included in the final literature review, of which five were RCTs and 11 were prospective clinical studies. Four studies discussed HBO as an adjunct to nonsurgical treatment of periodontitis, eight reported on HBO and osteoradionecrosis, and one examined HBO in bisphosphonate-related necrosis of the jaws.
CONCLUSIONS: HBO has shown superior efficacy compared to antibiotics as a prophylactic measure in preventing osteoradionecrosis (ORN) in patients with a history of high mandibular irradiation. Clinicians should consider referring such patients for HBO therapy before and after tooth extractions. However, for the surgical excision of existing ORN lesions, HBO therapy does not yield significant benefits but does not negatively impact outcomes either. Regarding the treatment of periodontitis patients, the variability among studies prevents definitive conclusions. HBO therapy as an adjunct to SRP in periodontitis treatment produces mixed results.
CONCLUSIONS: This study\'s clinical relevance lies in its exploration of the potential benefits of HBO for periodontal conditions. Also, it provides clinicians with insights into when and how to integrate HBO therapy into their treatment approaches, particularly for patients with a history of irradiation and those undergoing complex dental procedures.

Medication-related osteonecrosis of the jaw (MRONJ), a severe side effect caused by antiresorptive antiangiogenic medication, particularly bisphosphonates (BPs), has become a challenging disease with serious and profound effects on the physical and mental health of patients. Although it occurs with high frequency and is harmful, the exact mechanism of MRONJ remains unknown, and systematic and targeted approaches are still lacking. Maxillofacial surgeons focus on the etiology of osteonecrosis in the mandible and maxilla as well as the appropriate oral interventions for high-risk patients. Adequate nursing care and pharmacotherapy management are also crucial. This review provides a current overview of the clinicopathologic feature and research of MRONJ caused by BPs, with an emphasis on the potential mechanisms and current therapy and prevention strategies of the disease. We are of the opinion that an in-depth comprehension of the mechanisms underlying MRONJ will facilitate the development of more precise and efficacious therapeutic approaches, resulting in enhanced clinical outcomes for patients.

Dental implants are a predictable option to replace missing teeth. Patients on antiresorptive medications used to treat disorders associated with bone resorption may need dental implants to replace missing teeth. The data on implant failure in patients on antiresorptive medication requiring dental implants, is conflicting and limited. This systematic review aims to investigate if antiresorptive medications have any clinical impact on dental implant survival. Electronic databases were searched until May 2020. The focus question (PICOS): Participants: humans, Interventions: implant placement surgery in patients on antiresorptive medication, Comparisons: patients on antiresorptive medication vs control (patients not on antiresorptive medication), Outcomes: implant survival, and Study design: clinical studies. The protocol of this systematic review was registered in PROSPERO (CRD42020209083). Fourteen nonrandomized studies were selected for data extraction and risk of bias assessment using the ROBINS-1 tool. Only studies with a control were included for the meta-analysis, 8 articles were included in the meta-analysis using implant-level data, and 5 articles were included in the meta-analysis using patient-level data. There was no statistical significance between the 2 groups at the patient level based on 265 patients. However, there was a statistically significant difference at the implant level based on 2697 implants. Therefore, antiresorptive medications, mainly bisphosphonates (BPs), may significantly contribute to implant failure. Antiresorptive medications, especially BPs may reduce implant survival and impair the osseointegration of dental implants. Failed implants in patients on BPs may not lead to osteonecrosis and may be replaced with success.

UNASSIGNED: The application of blood concentrates has gained popularity in dentistry in recent years. Platelet-rich fibrin (PRF) has been discussed frequently due to a high content of growth factors and the option of chair-side manufacturing in a simple centrifugation process. PRF is free from adjuvants and inexpensive to produce. The number of studies reporting beneficial effects of PRF in various clinical applications such as alveolar ridge preservation, sinus floor elevation, management and prevention of medical-related osteonecrosis of the jaw, third molar extractions, and guided bone regeneration in dentistry has increased recently. However, to date, neither clinical recommendations nor guidelines are available. The present narrative review aims to summarize the level of evidence on the clinical application of PRF within the field of oral surgery and implantology.
UNASSIGNED: A literature search in Pubmed and Medline has identified 34 articles as a basis for this narrative review. The effectiveness of the clinical application of PRF has been analyzed for five indications within dentistry: medical-related osteonecrosis of the jaw, wisdom tooth extraction, guided bone regeneration, sinus floor elevation, and alveolar ridge preservation. The amount of data for third molar extractions, socket preservation, and guided bone regeneration is extensive. Less data were available for the use of PRF in combination with sinus floor elevations. There is a lack of studies with scientific evidence on PRF and medical-related osteonecrosis of the jaw; however, studies positively impact patient-related outcome measures. Most studies report on beneficial effects when PRF is additionally applied in intrabony defects. There is no evidence of the positive effects of PRF combined with bone graft materials during sinus floor elevation. However, some benefits are reported with PRF as a sole filling material.
UNASSIGNED: Many recently published studies show the positive clinical impact of PRF. Yet, further research is needed to ensure the validity of the evidence.

Invasive dental treatment in patients exposed to antiresorptive and antiangiogenic drugs can cause medication-related osteonecrosis of the jaw (MRONJ). Currently, the exact pathogenesis of this disease is unclear.
In March 2022, Medline (Ovid), Embase (Ovid), Scopus, and Web of Science were screened to identify eligible in vitro studies investigating the effects of antiresorptive and antiangiogenic compounds on orally derived cells.
Fifty-nine articles met the inclusion criteria. Bisphosphonates were used in 57 studies, denosumab in two, and sunitinib and bevacizumab in one. Zoledronate was the most commonly used nitrogen-containing bisphosphonate. The only non-nitrogen-containing bisphosphonate studied was clodronate. The most frequently tested tissues were gingival fibroblasts, oral keratinocytes, and alveolar osteoblasts. These drugs caused a decrease in cell proliferation, viability, and migration.
Antiresorptive and antiangiogenic drugs displayed cytotoxic effects in a dose and time-dependent manner. Additional research is required to further elucidate the pathways of MRONJ.

In the treatment and prevention of osteoporosis and more generally of neoplastic and metabolic pathologies affecting bone tissues, antiresorption drugs such as bisphosphonates and monoclonal antibody are used. Bisphosphonates have been linked to cases of osteonecrosis of the jaws since 2003 by Marx, with more and more evidence over the next two decades; together with bisphosphonate drugs, cases relating to the use of monoclonal drugs have been subsequently added. Among the main independent risk factors, we have extraction procedures in oral surgery that can affect both the mandible and the maxilla and the anterior or posterior sectors. The incidence of MRONJ treated with oral bisphosphonates ranges from 0.5% to 3% according to studies; this incidence would appear to be higher in patients treated with antiresorptive agents with neoplastic diseases. Many pathologies including those in which antiresorptive drugs are used show differences in prevalence in relation to sex; similarly, there could be differences in the incidence of cases of osteonecrosis based on gender in patients undergoing dentoalveolar surgery. Therefore, the objective of this systematic review and trial sequential analysis was to identify and quantify whether there is a proportionally greater risk of MRONJ in male or female subjects and whether there is evidence of greater involvement of osteonecrosis at several extraction sites, differentiating them into mandibular or maxilla and in the anterior or posterior sector. The revision protocol followed the indications of the Cochrane Handbook, and were recorded in Prospero, while the drafting of the manuscript was based on PRISMA. The results of the systematic review, after the study identification and selection process, included a total of 24 studies. The results of the meta-analysis reports: odds ratio (random effects model): 1.476 (0.684, 3.184) between male and female; odds ratio (random effects model): 1.390 (0.801, 2.412) between mandible and maxillary, and an odds ratio value of 0.730 (0.250, 2.137) between the anterior and posterior extraction sites. In conclusion, we can see that there was a trend in the onset of MRONJ as a complication of dentoalveolar surgical procedures, which proportionally mostly involved the male sex and the posterior mandibular sectors, however, this trend must be further confirmed by additional studies.

UNASSIGNED: To provide a concise review on risk factors, stages, pathophysiology, prevention and possible treatment options for both MRONJ and ORN individually.
UNASSIGNED: The review was conducted according to the \'Preferred Reporting Items for Systematic Reviews and Meta-Analyses\' (PRISMA) guidelines. A comprehensive search of the PUBMED, Ebsco, SCOPUS, WEB OF SCIENCE and NDH for articles published up until 2021 was performed. After screening and full text analyses, 44 studies were included in this review. Definition, risk factors, etiology, symptoms, stages, pathophysiology, prevention and possible management options were explored and highlighted in this article.
UNASSIGNED: Three studies described osteonecrosis of jaw (ONJ) in general, 15 studies described ONJ associated with radiotherapy and 26 studies described ONJ associated with medications. Both the two conditions (ORN) and (MRONJ) have relatively similar clinical presentations clearing the fact that a resemblance in clinical presentations does not necessarily denote a similar pathophysiology.
UNASSIGNED: However, various advancements have been made in the control and management of ONJ, but until and unless need for high tumoricidal doses exists, ONJ will certainly continue to remain as a clinical challenge demanding satisfactory treatment to improve the quality of life of the patient.

Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of antiresorptive or antiangiogenic agents, with no history of radiation or metastatic disease. Bisphosphonates (BF) and denosumab (DS) are widely used in adults for the management of patients with cancer and osteoporosis, and recently there has been an increase in their use in child and young patients for the management of disorders such as osteogenesis imperfecta (OI), glucocorticoid-induced osteoporosis, McCune-Albright syndrome (MAS), malignant hypercalcemia, and others. There are differences between case reports in adults compared to child and young patients related to the use of antiresorptive/antiangiogenic drugs and the development of MRONJ. The aim was to analyze the presence of MRONJ in children and young patients, and the relation with oral surgery. A systematic review, following the PRISMA search matrix based on the PICO question, was conducted in PubMed, Embase, ScienceDirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1960 and 2022, publications in English or Spanish, including randomized and non-randomized clinical trials, prospective and retrospective cohort studies, cases and controls studies, and series and case reports. A total of 2792 articles were identified and 29 were included; all of them published between 2007 and 2022, identifying 1192 patients, 39.68% male and 36.24% female, aged 11.56 years old on average, using these drugs mainly for OI (60.15%); 4.21 years on average was the therapy time and 10.18 drug doses administered on average; oral surgery was observed in 216 subjects, reporting 14 cases of MRONJ. We concluded that there is a low presence of MRONJ in the child and youth population treated with antiresorptive drugs. Data collection is weak, and details of therapy are not clear in some cases. Deficiencies in protocols and pharmacological characterization were observed in most of the included articles.