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Parenteral Ozone Therapy Combined with Topical Antimicrobials Enhances Tissue Repair in Mandibular Osteonecrosis of Elderly Female Rats.

Medication-related osteonecrosis of the jaws (MRONJ) remains a challenging complication associated with antiresorptive therapy, highlighting the need for effective adjunctive preventive strategies. This study evaluated the effects of systemic ozone therapy, alone or combined with topical 10% metronidazole paste or 2% chlorhexidine gel, on alveolar repair in a zoledronate-induced rat model of MRONJ. Forty-two ovariectomized female Wistar rats were allocated into seven experimental groups. Following mandibular first molar extraction, animals received systemic ozone therapy and/or topical antimic

Mitigating jaw osteonecrosis: bioactive glass and pericardial membrane combination in a rat model.

OBJECTIVES: Bisphosphonates (BFs) show clinical effectiveness in managing osteoporosis and bone metastases but pose risks of bisphosphonate-related jaw osteonecrosis (BRONJ). With no established gold standard for BRONJ treatment, our focus is on symptom severity reduction. We aimed to assess the preventive effects of bioactive glass and/or pericardial membrane in a preclinical BRONJ model, evaluating their potential to prevent osteonecrosis and bone loss post-tooth extractions in zoledronic acid (ZA)-treated animals. METHODS: Rats, receiving ZA or saline biweekly for four weeks, underwent 1st

Advanced biomaterial-based approaches for medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect linked to anti-resorptive and anti-angiogenic therapies, with an incidence of 4.34 % (6.22 % in oncology patients and 0.59 % in osteoporosis patients) based on a pooled analysis of 92 observational studies (2015-2020), characterized by persistent bone exposure and poor healing. Conventional treatment modalities often yield suboptimal outcomes, with recurrence and procedural morbidity. In recent years, biomaterial-based strategies have emerged as promising alternatives by targeting MRONJ's complex pathophysiolo

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… Zheng et al. showed that adipose-derived MSC exosomes suppressed M1 macrophage pyroptosis, a process triggering inflammatory cascades and impairing tooth socket healing, via inhibition of the NF-κB/NLRP3/IL-1β axis, and promoted bone and soft tissue regeneration through IL-1 receptor antagonist (IL-1RA …

Differential Zoledronate Adsorption by Commercially Available Biphasic Calcium Phosphate Bone Substitutes.

Background/Objectives: Osteonecrosis of the jaw, a non-healing wound, is a side effect in patients treated with nitrogen-containing bisphosphonates (e.g., zoledronate) after some oral procedures. Considering zoledronate toxicity in surgical wounds and the capacity of calcium phosphate synthetic compounds to adsorb it, the aim of this work was to demonstrate and elucidate the mechanism underlying this adsorption. Methods: Four different calcium phosphate synthetic bone substitutes were used in this study: AdBone® BCP (0.5-1 mm), Guidor® easy-graft (0.5-1 mm), Maxresorb® (0.5-1 mm) and Maxresorb

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

OBJECTIVE: Medication-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 antireso

Immediately loaded distally cantilevered fixed mandibular prostheses supported by four implants placed in both in fresh extraction and healed sites: 2-year results from a prospective study.

OBJECTIVES: To evaluate the outcome of immediately loaded distally cantilevered mandibular full-arch prostheses according to the 'all-on-four' concept supported by implants placed in both fresh extraction and healed sites. MATERIAL AND METHODS: A prospective study was conducted in 24 patients with extraction of all remaining mandibular teeth and placement of 4 implants per patient (2 mesial axial and 2 distal tilted) for full-arch mandibular restorations. Implants were inserted in fresh extraction sockets 2.3 ± 1.0 per patient and 1.7 ± 1.0 implants in healed sites. Implants placed in fresh e

Bisphosphonate-Related Osteonecrosis of the Jaw and Oral Microbiome: Clinical Risk Factors, Pathophysiology and Treatment Options.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesio

Management of Tooth Extraction in Patients Taking Antiresorptive Drugs: An Evidence Mapping Review and Meta-Analysis.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a well-known severe adverse reaction of antiresorptive, antiangiogenic or targeted therapies, and usually occurs after tooth extraction. This review is aimed at determining the efficacy of any intervention of tooth extraction to reduce the risk of MRONJ in patients taking antiresorptive drugs, and present the distribution of evidence in these clinical questions. METHODS: Primary studies and reviews were searched from nine databases (Medline, EMBase, Cochrane Library, Scopus, WOSCC, Inspec, KCI-KJD, SciELO and GIM) and two regi

Chinese expert consensus on the diagnosis and clinical management of medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a side effect that occurs after treatment for systemic diseases. However, most institutions currently rely on empirical methods to make diagnosis and treatment plans, and there is a lack of consensus or guidelines for the classification, staging and treatment of MRONJ in China. To address this gap and improve prognosis, an expert panel representing 11 renowned domestic medical colleges and affiliated hospitals in China was convened. The panel made a comprehensive literature review of previous treatment experiences and research findings to

Increased risk of bisphosphonate-related osteonecrosis of the jaw in patients with Sjögren's syndrome: nationwide population-based cohort study.

OBJECTIVE: The aim of this study was to explore whether patients with Sjögren's syndrome (SS) were susceptible to bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) after tooth extraction in the entire population of Taiwan. DESIGN: A nationwide population-based retrospective cohort study. SETTING: Data were extracted from Taiwan's National Health Insurance Research Database (NHIRD). METHODOLOGY: Medical conditions for both the study and control group were categorised using the International Classification of Diseases, 9th Revision. ORs and 95% CIs for associations between SS and o

Medication-Related Osteonecrosis of the Jaw: Successful Medical Management of Complex Maxillary Alveolus with Sinus Involvement.

Medication-related osteonecrosis of the jaw (MRONJ) in cancer patients presents a considerable challenge in management. Current management is primarily based on interventions in a limited number of cases assessing a single approach. Medical management typically is reported to include antimicrobial therapy with or without surgery. Advances in the understanding of pathogenesis have led to the investigation of additional medical interventions for early-stage necrosis. We present 3 patients with advanced-stage MRONJ of the maxilla using combined medical modalities including antimicrobial therapy,

Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients.

Tooth extraction has been avoided since it has been considered a major risk factor for medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may also develop from tooth that is an infection source. This study aimed to clarify whether tooth extraction is a risk factor for the development of MRONJ in cancer patients receiving bone-modifying agents (BMAs). This retrospective observational study included 189 patients (361 jaws) from two hospitals. The risk factors of MRONJ were identified by comparing patient characteristics between those who did and did not develop MRONJ. Furthermor

Oral squamous cell carcinoma vs. medication-related osteonecrosis of the jaw in patients assuming bone-modifying agents: a diagnostic challenge in a multi-hospital case series.

BACKGROUND: Despite advances in the diagnosis of oral squamous cell carcinoma (OSCC), most cases are diagnosed in advanced stages, influencing negatively the patient's prognosis. The absence of specific signs and symptoms contributes to the diagnostic delay of OSCC, often leading to confusion with various oral conditions, including, in patients with a history of bone modifying agents (BMA) and/or anti-angiogenic (AA) molecules, the Medication-Related Osteonecrosis of the Jaw (MRONJ). This study aims to investigate the characteristics of OSCC and MRONJ, focusing on clinical and radiological fea

Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw.

Bisphosphonates (BPs) are inhibitors of osteoclast-mediated bone resorption used for the treatment of multiple myeloma (MM) patients with osteolytic lesions. Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is an infrequent drug-caused adverse event of these agents. Long noncoding RNAs (lncRNAs) are a set of more than 200 base pairs, noncoding RNA molecules, which are critical posttranscriptional regulators of gene expression. Our study was aimed at evaluating 17 lncRNAs, whose targets were previously validated as key elements in MM, bone metabolism, and angiogenesis in MM subjects witho

Bisphosphonate-related osteonecrosis of the jaw in metastatic breast cancer patients: a review of 25 cases.

BackgroundIntravenous bisphosphonates have been used in metastatic breast cancer patients to reduce pathologic bone fracture and bone pain. However, necrosis of the jaw has been reported in those who received intravenous bisphosphonates. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is caused by dental extraction, dental implant surgery, and denture wearing; however, it occurs spontaneously. The purpose of this study was to report BRONJ in metastatic breast cancer patients.MethodsConsecutive 25 female patients were referred from the Department of Oncology from 2008 to 2014 for jaw bo

Bromelain has significant clinical benefits after extraction of the third molar during chemotherapy in patients with hematologic tumor.

The purpose of this study was to investigate the application of bromelain in the treatment of pain, swelling, and limited mouth opening in patients with hematologic tumor after extraction of the third molar during chemotherapy. We recruited 72 patients with hematologic tumor who were treated by oral and maxillofacial surgery in our hospital, and third molar extraction was performed under local anesthesia. After extraction, patients in the control group were treated with cold - hot compress and patients in the experimental group were treated by oral administration of bromelain. One, three, and

From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights.

Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte colony-stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone h

Pulp and periapical disease as a risk factor for osteonecrosis of the jaw: a national cohort-based study in Korea.

PURPOSE: This longitudinal cohort study aimed to evaluate the relationship between osteonecrosis of the jaw and pulp and periapical disease in patients who were administered bisphosphonates. METHODS: Using data from a nationwide cohort, we examined the association among dental caries, pulp and periapical disease, and osteonecrosis of the jaw in women aged >50 years who received bisphosphonates for more than 1 year between 2002 and 2015. Because of ambiguities in the diagnosis of osteonecrosis of the jaw in population-based data, we operationally defined and categorized the condition into esta

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis - A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso).

Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasiv

Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS.

CONTEXT: Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ). OBJECTIVE: We aimed to identify the differences various aspects of MRONJ among distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in eac

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… Furthermore, BPs can suppress the migration of oral epithelial cells, a step crucial for tooth socket closure ( 31 ). …