Medication-related Osteonecrosis Of The Jaw Research Articles

Potential role of comprehensive dental care in preventing medication related osteonecrosis of the jaw (MRONJ): a single centre study

ObjectiveMedication-related osteonecrosis of the jaw bones (MRONJ) is a well-known complication of antiresorptive and antiangiogenic drugs. Since the first report, more occurrences of MRONJ have been described worldwide. Dental extraction has been described by many studies as one of the risk factors for MRONJ. Comprehensive dental care (CDC) is a preventive dental method provided to patients prior to drug commencement. This study aims to determine the association between CDC and MRONJ. Patients and methods. A retrospective analysis was performed on 75 medical records of patients on antiresorptive and/or antiangiogenic drugs between February 2018 and May 2021. Demographics and clinical and radiographic data were collected. Univariate and multivariate analyses were performed to determine the factors associated with MRONJ.ResultsOf the 75 patients who met the inclusion criteria, 11 (14.7%) developed MRONJ. Three out of 11 patients (27.2%) developed MRONJ spontaneously, while eight patients (72.8%) developed it after trauma from dentures or dental extractions. Following a binary logistic regression analysis, the lack of CDC was identified as a significant predictor of MRONJ. Patients who did not receive CDC had an odds ratio of 8.64 (95% confidence interval (CI): 1.27–58.62, p = 0.03). However, dental extraction did not show a statistically significant association with MRONJ in both the univariate and multivariate analyses.ConclusionCDC before treatment with antiresorptive and antiangiogenic drugs is a potentially effective preventive method for reducing MRONJ. Dental extraction was not a significant factor in relation to MRONJ.

The provision of dental extractions in patients with established or a history of medication-related osteonecrosis of the jaw.

Patients with existing or a history of medication-related osteonecrosis of the jaw (MRONJ) are considered to be at a higher risk of further developing MRONJ, particularly if dental extractions are necessary. It is assumed that their underlying risk factors predispose them to developing MRONJ and they are allocated into an 'elevated risk group'. There is no evidence to quantify this risk level; however, it has led to an avoidance of dental extractions in this cohort. However, avoidance of dental extractions is not a realistic treatment option to prevent MRONJ and there is emerging evidence that inflammatory dental disease, such as peri-apical pathology or periodontal disease, can trigger the pathogenesis of MRONJ. The current case series retrospectively reviewed 28 patients with existing or a history of MRONJ who underwent dental extractions (n = 65) via our departmental protocol, which includes elective circumferential socket alveoplasty and primary closure. Our outcomes show that MRONJ did not develop at the new extraction site, with a post-operative review period of at least six months. These results provide promising evidence that dental extractions can be performed in this group of patients with <1% risk of developing MRONJ at the new surgical site, if appropriate measures are undertaken.

An institutional protocol including socket alveoplasty and primary closure following dental extractions for patients with an elevated risk of developing medication-related osteonecrosis of the jaw.

Background The purpose of this study was to evaluate the outcomes of alveoplasty and primary closure following dental extractions in patients with an elevated medication-related osteonecrosis of the jaw (MRONJ) risk.Study design A retrospective review of 46 patients with an elevated MRONJ risk was conducted. This included a total of 124 teeth extracted, due to unrestorable caries (n = 46; 37%) and peri-apical pathology (n = 44; 35%).Results Our results showed 0% (n = 0) of patients in our cohort developed MRONJ post-operatively. Most patients were being treated with intravenous zoledronic acid for breast cancer (n = 23; 50%), with an average of 15 doses (range 1-72).Conclusions This study supports the use of alveoplasty and primary closure for patients with an elevated MRONJ risk. The authors highlight the importance of pre-operative cone beam computed tomography imaging, optimisation of immune status, post-operative prophylactic antibiotics, and the delay of bone modifying agents recommencement as influential factors in mitigating risk and favouring successful outcomes.

Long-Term Risk of Medication-Related Osteonecrosis of the Jaw (MRONJ) After Bisphosphonates and/or Denosumab in Metastatic Breast Cancer Patients

Recently published data identified cancer patients with bone metastases receiving continuous monthly antiresorptive drugs (bisphosphonates and/or denosumab) as patients at high risk for Medication-Related Osteonecrosis of the Jaw (MRONJ), even with late onset. A retrospective multicenter study was conducted between 2000 and 2020 at all breast centers across Tyrol (Austria), screening all patients with breast cancer and bone metastases receiving antiresorptive therapy. The MRONJ incidence was found to be considerably high in patients receiving denosumab (11.6%-16.3%), with an elevated cumulative incidence at 6 years. This commentary underlines some important results of the study and proposes further evaluation of the group of patients receiving a sequence of bisphosphonates and denosumab. Furthermore, other interesting data could come from patients treated in the last decade, receiving more effective anticancer treatments but also more frequently denosumab, in comparison with patients treated in previous years.

Magnesium Nanocomposite Hydrogel Reverses the Pathologies to Enhance Mandible Regeneration.

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

Bone regeneration after adjuvant therapies for medication-related osteonecrosis of the jaws (MRONJ): a pre-clinical study

Bone regeneration after adjuvant therapies for medication-related osteonecrosis of the jaws (MRONJ): a pre-clinical study

Geographic residence of patients with medication-related osteonecrosis of the jaw.

135 Background: Bone-modifying agents (BMAs) are utilized to reduce the risk of skeletal-related events in patients with bone metastases. Medication-related osteonecrosis of the jaw (MRONJ) is a rare but difficult to treat adverse event of BMAs. There are known patient and treatment related risk factors for development of ONJ, however, little is known on social and geographic risks. In patients with bone metastases and concurrent MRONJ, we seek to describe differences in patient's geographic residence (rural versus urban) with other social factors as secondary outcomes. Methods: We conducted a retrospective chart review of Atrium Health Wake Forest Baptist Comprehensive Cancer Center patients in the date range of 01/01/2013 to 11/01/2023. Included were patients with metastatic breast cancer, metastatic prostate cancer or multiple myeloma who had a diagnosis of MRONJ. We recorded Rural-Urban Commuting Area (RUCA) codes, the Area Deprivation Index (ADI), age, race, ethnicity, smoking status, alcohol use, body mass index, insurance status, type of cancer, type of BMA, and cumulative dosing of BMAs. Patients were defined as rural or urban based on criteria from the health resources and services administration website. Relative socioeconomic advantage versus disadvantage was determined by the patients’ ADIs with a decile rank from 1-10 for state ADIs and a percentile rank of 1-100 for national ADIs. SAS software (version 9.4) was used for data analysis (2023, SAS Institute Inc, Cary, NC). Results: A total of 88 patients met inclusion criteria. 64% of patients lived in urban areas and 36% in rural. Demographic features of the identified patients are listed in table 1. MRONJ patients from both urban and rural areas had an above average national and state ADI, with a trend toward higher ADIs in rural locations compared to urban locations; mean of 6.7 vs 5.3 state ADI and mean 70.6 vs 62.0 national ADI, for rural and urban patients respectively. There were no statistically significant differences between rural and urban patients in any of the demographic or health-related characteristics we examined. Conclusions: Patients with bone metastases and MRONJ in our cohort demonstrate relative socioeconomic disadvantage in comparison to national and state averages. In comparing the rural with urban patients, however, we observed relatively similar profiles. Patient characteristics by rural/urban status. Rural (n=32) Urban (n=56) Age in years (mean, sd) 64 (11.3) 65 (10.9) Sex, N (%) Male 19 (59) 29 (52) Female 13 (41) 27 (48) Race, N (%) Non-Hispanic White 30 (93.8) 40 (71.4) Non-Hispanic Black 1 (3.1) 11 (19.6) Hispanic 1 (3.1) 3 (5.4) Non-Hispanic Asian 0 (0.0) 1 (1.8) Other 0 (0.0) 1 (1.8) State ADI (mean, sd) 6.7 (2.4) 5.5 (2.7) National ADI (mean, sd) 70.6 (16.9) 62.0 (23.8) Former/current smoker, N (%) 18 (56.3) 25 (44.6) Medicaid/Medicare, N (%) 16 (50.0) 16 (28.6) Months on BMA (mean, sd) 37.2 (35.5) 40.3 (38.2)

Biofluorescence imaging system (BIS) Guided surgery for MRONJ: A Case Series on the Preservation of Teeth and Implants: Biofluorescence imaging system guided MRONJ surgery

The decision of surgical margin for Medication-Related Osteonecrosis of the Jaw (MRONJ) surgery is challenging. Recently, a method involving biofluorescence imaging system (BIS) has been reported for its application in MRONJ surgery to live detection of pathologic bone tissue from vital bone, which cannot be distinguished during conventional surgery. This case series aimed to assess the outcomes of adjacent teeth and implants near the lesion site in MRONJ patients who underwent BIS-guided MRONJ surgery. This retrospective study was assessed the radiographic and clinical outcomes of seven patients who underwent MRONJ surgery with BIS guidance but chose not to remove adjacent teeth or implants near the lesion. A total of seven patients (1 male, 6 females, 77.2 ± 4.7 years) were included in the study. Four implants and four teeth adjacent to the lesion were preserved. Over an average duration of 8.7 months, all subjects exhibited normal soft tissue healing and function without any complications. In conclusion, the BIS guided MRONJ surgery can be considered a minimally invasive and effective approach.

Application of bone perforation in the surgery of medication-related osteonecrosis of the jaw in stage Ⅱ.

This study aimed to explore the effect of surgery combined with bone perforation for treating stage Ⅱ medication-related osteonecrosis of the jaw (MRONJ). A total of 21 patients with stage Ⅱ mandibular MRONJ who underwent surgical treatment from June 2020 to June 2023 were included in this study. Retrospective analysis was conducted on their clinical data, including gender, age, primary disease, drug name and administration method, pre-surgery drug cessation, and prognosis. The cohort comprised 14 males and 7 females, with an average age at onset of 68.33±10.74 years. According to the guidelines of the American Association of Oral and Maxillofacial Surgeons, the included patients had stage Ⅱ mandibular MRONJ. The treatment approach consisted of partial mandibulectomy combined with bone perforation techniques, ensuring tension-free suturing of soft tissues. Follow-up was performed regularly, and the curative effect was evaluated. The SF-12 health survey was used to assess the quality of life for all patients before and after surgery. A total of 21 patients were followed up for 8-38 months after surgery, and the mucosal healing of 17 patients was good (80.95%). The postoperative quality of life score (83.62±5.90) was significantly higher than that before operation (63.67±4.70, P<0.05). Surgery combined with bone perforation te-chnique is an effective treatment method with high success rate in refractory stage Ⅱ MRONT patients.

Autologous platelet concentrates as adjuvant in the surgical management of medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is an infectious side effect associated with bisphosphonates and monoclonal antibodies (denosumab, immune modulators, and antiangiogenic medications). Adjunctive therapies for the surgical management of MRONJ include autologous platelet concentrates (APCs). These APCs serve as a source of various cells and growth factors that aid tissue healing and regeneration. This review evaluated the use of platelet-rich plasma (PRP), plasma-rich in growth factors (PRGF), and leukocyte- and platelet-rich fibrin (L-PRF) as adjuvant therapies for the surgical management of MRONJ by conducting analyses on the results of 58 articles. Compared to surgical treatment alone, the application of PRP and L-PRF after surgery appears to increase healing in the management of patients with MRONJ. No studies have reported unhealed lesions as a result of surgical treatment of MRONJ with PRGF application or compared it with surgical treatment alone. The overall results of this review have shown favorable healing rates of MRONJ lesions managed with the application of APCs after surgical treatment; however, significant methodological limitations may limit the scientific evidence supporting their use. Further randomized controlled trials with strict criteria are needed to establish the extent to which APCs can improve wound healing and quality of life in patients with MRONJ requiring surgical treatment.

Oral and Gingival Crevicular Fluid Biomarkers for Jawbone Turnover Diseases: A Scoping Review

Gingival crevicular fluid (GCF) and oral fluid have emerged as promising diagnostic tools for detecting biomarkers. This review aimed to evaluate the existing literature on using oral fluids as a source of biomarkers for bone turnover diseases affecting the jawbone. A comprehensive search strategy was executed between August 2014 and August 2024 across five major databases (Web of Science, EBSCOhost Dentistry &amp; Oral Sciences Source, Cochrane Library, Scopus, and PubMed) and grey literature sources. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was applied. The screening was facilitated using Rayyan at rayyan.ai and Endnote X20 software tools, culminating in the evaluation of 14,965 citations from databases and 34 from grey literature. Following rigorous scrutiny, 37 articles were selected for inclusion in this review, encompassing diseases such as periodontitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoporosis. The quality of the included observational studies was assessed using the Revised Risk of Bias Assessment Tool for Non-Randomized Studies (RoBANS 2). Interleukin-1 beta (IL-1β), sclerostin, osteoprotegerin (OPG), and interleukin-34 (IL-34) emerged as significant biomarkers in GCF, and they were mainly from periodontitis and osteoporosis. Osteocalcin (OC), IL-1β, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), OPG, and matrix metalloproteinase-9 (MMP-9) were significant in oral fluid or saliva, and they were from periodontitis, MRONJ, and osteoporosis. These findings underscore the potential use of oral fluids, which are regarded as non-invasive tools for biomarker identification in bone turnover. Many biomarkers overlap, and it is important to identify other specific biomarkers to enable accurate diagnosis of these conditions.

Atypical fractures at non-classical sites associated with anti-resorptive therapy: A Systematic Review.

Osteoporosis is common, affecting more than 20% of women and 6% of men globally over the age of 50 (1). Anti-resorptive drugs, bisphosphonates and denosumab, have been effective treatments for osteoporosis for more than 30years. Rare complications of anti-resorptive therapy include medication-related osteonecrosis of the jaw and atypical femur fractures (AFF). The American Society for Bone and Mineral Research (ASBMR) proposed a case definition for these atypical femoral fractures in 2010, which was updated in 2013. However, atypical fractures at non-classical sites have been increasingly described. We aimed to systematically identify atypical fracture cases, excluded from the ASBMR AFF case definition in patients receiving anti-resorptive medication for longer than three years. A structured search of electronic databases, including PubMed, Medline (Ovid), Embase (Ovid), Cochrane and Web of Sciences, and hand-searching of conference abstracts was undertaken. All full-text articles written in English describing an atypical fracture in patients (aged >18years) and receiving anti-resorptive medication for >3years were included, with data extracted and analysed by two independent reviewers. Sixty-six articles were identified, describing 151 cases of atypical fractures in 114 individuals. The most frequent fracture site was the ulna, followed by the tibia. All patients were taking anti-resorptive treatment prior to or at the time of fracture, most frequently alendronate monotherapy (44%). Most commonly, fractures were transverse in nature (95%), following minimal or no trauma (96%), non-comminuted (98%) with cortical thickening of the surrounding bone (69%). Anti-resorptive treatment was ceased following atypical fracture in the majority (89%). Atypical fractures are rare and should not deter physicians from appropriate anti-resorptive therapy for osteoporosis. However, clinicians should be alert to their presence, at additional sites to the femur. An update of the current ASBMR AFF case definition to include other skeletal sites could be timely.

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction.

Bridging the gap — Establishing a dental-oncology service in a cancer centre

Dental disease remains the most common non-communicable disease worldwide. It predisposes patients to significant morbidities following bone modifying agents or radiation therapy to the head and neck. Preventative dental regimes effectively reduce the risk of both medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) in these patients. Co-ordination of routine dental care as a component of mainstream oncology treatment optimises long term outcomes for oncology patients. This case series offers insights into patient, institutional and social difficulties that challenge the dental-oncology interface. These obstacles and subsequent resolutions experienced whilst establishing a dental-oncology service in a cancer centre highlight the importance of effective multidisciplinary lead care for oncology patients. It reinforces the need for structured, supported dental pathways for these oncology patients.

Medication-related osteonecrosis of the jaw: a retrospective single center study of recurrence-related factors after surgical treatment

ObjectivesTo provide an overview of the features of patients with medication-related osteonecrosis of the jaw (MRONJ) and explore recurrence-related factors after surgery.Materials and methodsAll pathological records of patients diagnosed with osteonecrosis or osteomyelitis of the jaw were reviewed. Only patients who had a history of use of medication related to bone turnover were included. All demographic and clinical characteristics were collected during review. Univariate and logistic regression analyses were performed to evaluate the associations between risk factors and recurrence. A p value < 0.05 was considered to indicate statistical significance in all analyses.ResultsA total of 313 patients were ultimately included. Most patients (89.14%) underwent bone turnover-related treatment due to malignancy. The breast and prostate were the most common locations of primary tumors in females and males, respectively. Almost all MRONJ patients experienced inflammatory symptoms. Recurrence occurred in 55 patients at 60 locations. The total recurrence rate was 16.85%, with no significant differences between the maxilla and mandible. Extensive surgery and flap transfer were strongly related to a lower recurrence risk. Nearly 80% of patients had recurrence-related symptoms within 6 months.ConclusionWhen MRONJ is treated with surgical methods, extensive resection and flap transfer can reduce recurrence risk. Six-month follow-up is needed to exclude recurrence after surgery.Clinical relevanceThis study revealed the surgical-related risk factors, such as extensive surgery and flap transfer, when treating MRONJ patients, and 6-month follow-up is needed to detect recurrence. This could provide clinical guidance for head and neck surgeons.

A Multi-Center Observation Study on Medication-Related Osteonecrosis of the Jaw (MRONJ) in Patients with Osteoporosis, and Other Non-Malignant Bone Diseases, in Northwestern Italy over 16 Years.

To assess the number of new cases of Medication-Related Osteonecrosis of the Jaw (MRONJ) among patients with osteoporosis and other non-malignant bone diseases in Northwestern Italy between 2007 and 2022. MRONJ cases were collected from referral centers in a population of 4.5 million. We analysed the number of new MRONJ cases per year, type of disease, administered drugs, duration of therapy (when available), and onset time of disease. We analysed 198 cases (out of 1071 total MRONJ cases); diseases included osteoporosis (87%), rheumatoid arthritis (5%), their association (4%), Paget's disease, and other various diseases (4%). Patients received bisphosphonates alone (74%), or denosumab alone (6%), or a sequence of different drugs (20%). The number of new cases increased over five years from 2 (2003-2007) to 51 (2008-2012), 65 (2013-2017), and 79 (2018-2022), and the percentage increased from 1% to 14%, 20%, and 29% of the total cases. The number of new MRONJ cases per year among patients with non-malignant diseases is rapidly increasing all around the world, though underestimation cannot be excluded. In this study, we describe epidemiological and clinical characteristics of patients, and the drug most frequently involved in MRONJ cases in our region over a long period, allowing a comprehensive view of the progression of the disease. Greater collaboration among specialists is needed for correct and early diagnosis to improve measures potentially reducing disease incidence and to limit quality of life deterioration in patients with osteoporosis and other non-malignant diseases.

Platelet-Rich Plasma in the Prevention and Treatment of Medication-Related Osteonecrosis of the Jaw: A Systematic Review and Meta-Analysis.

Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication associated with bisphosphonates, impacting jaw osteoclasts, and causing altered bone remodelling. Prevention involves stabilizing systemic pathology, considering antiresorptive therapies, and exploring platelet-rich fibrin (PRF) for wound healing and tissue regeneration. The study aims to assess the efficacy of PRF in MRONJ treatment and highlight research gaps for more robust investigations. Following PRISMA and MOOSE guidelines, this systematic review and meta-analysis included English publications from 2013 to 2023, employing a systematic search in databases such as MEDLINE, Scopus, and Web of Science. Quality assessment used the Cochrane Collaboration's tool and the NOS, with the main meta-analysis concentrating on PRF-treated MRONJ cases, assessing resolution rates, and prioritizing healing outcomes and infection absence as primary endpoints. The study, encompassing 11 articles and 480 participants with MRONJ, demonstrated that in stage 1 procedures, PRF significantly outperformed conventional medical treatments (OR: 2.93, 95% CI: 1.54-5.59, P=0.001), particularly at the mandible site (OR: 1.65, 95% CI: 0.86-3.17, P=0.13). PRF also exhibited significantly superior healing outcomes compared with conventional medical treatments (OR: 4.45, 95% CI: 1.58-12.53, P=0.005), supporting its consideration as a valuable alternative in specific MRONJ management scenarios. This study highlights PRF's effectiveness in early MRONJ interventions and specific anatomic sites, despite acknowledged limitations, emphasizing the need for further research, and supporting its consideration in MRONJ surgical management.

Evaluation of jaw pathologies of patients with medication-related osteonecrosis of the jaw using a computer program to assess the bone scan index: comparison of standardized uptake values with bone SPECT/CT.

The aim of this study is to investigate the jaw pathologies of patients with medication-related osteonecrosis of the jaw (MRONJ) using a computer program to assess the bone scan index (BSI), especially comparison of standardized uptake values (SUVs) with bone single-photon emission-computed tomography/computed tomography (SPECT/CT). Sixty-three patients with MRONJ underwent bone SPECT/CT in this prospective study. BSI and high-risk hot spot as bone metastases in the patients with MRONJ were evaluated using a computer program for BSI that scanned SPECT/CT and automatically defined the data. The maximum and mean SUVs with SPECT/CT were obtained using commercially available software. Statistical analyses were performed by Pearson chi-square test, Mann-Whitney U-test, or one-way analysis of variance with Tukey's honestly significant difference test. A P value lower than 0.05 was considered statistically significant. The maximum and mean SUVs for a high-risk hot spot of the jaw with MRONJ [28.2 ± 10.2 and 11.7 ± 3.8; n = 6 (6/63 : 9.5%)] were significantly higher than those for a low-risk hot spot [18.5 ± 6.4 and 6.2 ± 1.9; n = 23 (23/63 : 36.5%)] and no-risk hot spot [14.2 ± 9.4 and 5.3 ± 5.1; n = 34 (34/63 : 54.0%)], respectively. The computer program for BSI indicated that 9.5% of the jaw with MRONJ were false positive of bone metastases. The study suggests that high-risk hot spots of the jaw with MRONJ depend on the SUVs.

Introduction and overview on autogenous Platelet concentrates.

This special issue on autologous platelet concentrates (APCs) provides clinicians with an overview on the current understanding of the use of these biomaterials for soft and hard-tissue regeneration. The included papers summarize scientific evidence and the clinical findings, presented in simple tables that outline potential benefits including Patient Reported Outcome Measures (PROMs). This approach enables clinicians to assess clinical relevance and researchers to identify significant gaps in the literature. The first part provides a comprehensive summary of the basic science surrounding APC, with particular focus on their preparation methods. Clear recommendations are outlined, which are crucial for obtaining high-quality APCs, alongside an exploration of how APCs may influence both soft and hard tissue healing processes. Part 2 delves into the clinical evidence for the potential benefits of APCs across a range of applications: alveolar ridge preservation, sinus floor elevation, periodontal plastic surgery, guided tissue regeneration, guided bone regeneration, the healing of Medication-Related Osteonecrosis of the Jaw (MRONJ), and endodontic surgery. In the part 3, the discussion turns to the effects of APCs on the healing of extra-oral wounds, including diabetic foot ulcers, venous leg ulcers, pressure injuries, burns, and more. For those clinicians persuaded by the evidence, the fourth section offers a detailed, step-by-step flowchart for each treatment modality, providing a clear guide for clinical application.

Medication-Related Osteonecrosis of the Jaw: A Systematic Review of Case Reports and Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare condition, typically seen in patients receiving antiresorptive or antiangiogenic drugs. This study aims to synthesize reports and case series of MRONJ regarding sociodemographic and clinical characteristics and to evaluate the effectiveness of the treatments applied. Following PRISMA guidelines, a search for case reports and case series was carried out in the PubMed-Medline database until March 2024. A total of 88 articles were included in this review, in a total of 151 cases. The key findings reveal that females were the most affected individuals (71% of the cases) with the average age at diagnosis being 66.27 years with a standard deviation of ±13.03. Stage 2 was the most observed stage, in 43% of cases, and zoledronic acid was the most commonly used drug (32% of cases). The oral route was the most common route of administration, in 26% of cases, with an average administration duration of 60.88 months (standard deviation ± 50.92). The mandible was the most commonly affected anatomical location (in 60% of cases). Amoxicillin + clavulanic acid (875 mg + 125 mg) and chlorhexidine (0.12%) were the most used antibiotics and mouthwash, with 16% and 26% of the cases, respectively. Surgical debridement was the most common surgical procedure, in 32% of cases, while the use of an L-PRF membrane was the most prevalent unconventional treatment, in 21% of cases. This study identified a statistically significant relationship between unconventional treatments and the cure of MRONJ (p < 0.001), indicating the need for further research to confirm these results.