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Osteonecrosis of the jaw (ONJ) is associated with high-dose bisphosphonate therapy in patients with cancer, and has also been linked to bisphosphonate use in patients with osteoporosis. In this Review, the authors examine the epidemiology and pathogenesis of ONJ. Osteonecrosis of the jaw (ONJ) is defined as exposed bone in the oral cavity that persists despite appropriate therapy. Over the past decade, ONJ has been reported in about 5% of patients with cancer receiving high-dose intravenous bisphosphonates, and more recently in similar patients treated with denosumab, another potent inhibitor of osteoclastic bone resorption. The condition has also been described in patients treated with bisphosphonates for benign diseases, such as osteoporosis, but whether bisphosphonates or denosumab increase the incidence above that seen in untreated patients of comparable age and frailty is yet to be established. The pathogenesis of ONJ is uncertain: the toxic effects of bisphosphonates in a wide variety of cells could increase susceptibility to infections in the oral cavity or impair mucosal healing, and denosumab might interfere with monocyte and macrophage function. Local osteolysis is an important defense against infection on bone surfaces that is blocked by both bisphosphonates and denosumab. Preventive dentistry prior to high-dose antiresorptive therapy is a critical measure in cancer patients, but is not usually justified in patients with osteoporosis. The management of established ONJ lesions is problematic: the greatest success seems to come from vigorous antimicrobial therapy with judicious use of surgical debridement. Key Points Osteonecrosis of the jaw (ONJ) is defined as the presence of exposed bone in the mouth that persists despite appropriate therapy ONJ is primarily a problem encountered in patients with cancer receiving high-dose intravenous bisphosphonates for the prevention of skeletal-related events, of whom about 5% develop the condition ONJ has now been reported at a similar frequency in patients with cancer treated with denosumab, a monoclonal antibody against RANKL ONJ has also been reported in patients treated with bisphosphonates for osteoporosis, but it is not yet established whether bisphosphonates increase the incidence above that seen in untreated patients of comparable age and frailty The pathogenesis of ONJ is uncertain, but local toxicity from bisphosphonates or blockade of the normal osteolytic response to infection on a bone surface might be important factors Preventive dentistry prior to initiation of high-dose antiresorptive therapy is important in patients with cancer, but is not usually justified in patients with osteoporosis

Fatty degenerative osteonecrosis of the jaw (FDOJ) is a chronic, aseptic inflammatory condition that is characterized by molecular disruptions in bone metabolism and necrotic bone marrow within the jawbone cavities. In contrast to the overt clinical signs typically observed in osteopathies, FDOJ frequently presents with a “silent inflammation” phenotype. The electronic databases PubMed, Scopus, and Embase were searched using appropriate search terms, and the methodology was performed according to PRISMA-ScR guidelines. The elevated expression of inflammatory mediators, particularly C-C motif Chemokine Ligand-5/Regulated on Activation, Normal T Cell Expressed and Secreted (CCL5/RANTES), fibroblast growth factor-2, and interleukin-1 receptor antagonist, distinguishes FDOJ at the molecular level and links it to systemic inflammatory and autoimmune diseases. These immunohistochemical markers play a pivotal role in the pathogenesis of chronic inflammation, immune response regulation, and abnormal bone remodeling. Advanced diagnostic tools, such as conebeam computed tomography and trans-alveolar ultrasonography, facilitate the detection of pathological changes that are not easily discernible with conventional radiography. Surgical intervention remains the primary treatment modality, often complemented by therapies that target these molecular pathways to modulate chronic inflammation. This article underscores the importance of integrating molecular diagnostics, advanced imaging, and clinical data for effective FDOJ detection and management.

Development of quantitative analysis software has enabled application of several standardised uptake values (SUV) for bone analysis in single photon emission computed tomography (SPECT). The present retrospective study aimed to develop a reliable method of monitoring bone inflammatory activity in antiresorptive agent-related osteonecrosis of the jaw (ARONJ) using SPECT quantitative analysis software. Fifteen ARONJ patients underwent SPECT before and after anti-inflammatory therapy. We calculated the mean maximum SUV (SUVmax) of the bilateral cranial bones using quantitative analysis software and used this as the control [C]. We attempted to adjust the SUVmax of the lesion [L] as follows: adjusted SUVmax ( aSUVmax ) = [ L ] − [ C ] . The optimum threshold to calculate the metabolic bone volume (MBV) (cm 3 ) was [C] + 3. The threshold values obtained for each case were input to calculate MBV at each osteomyelitis site. Retrospectively, we compared aSUVmax and MBV of each patient’s ARONJ before and after anti-inflammatory therapy. The patients’ high aSUVmax or large MBV of the ARONJ reduced rapidly, reflecting individual clinical findings after treatment. Application of SPECT quantitative analysis software to monitor bone inflammatory activity in ARONJ could improve the prognosis-deciding abilities of clinicians and enable them to treat ARONJ effectively.

Odontogenic cysts and osseous lesions are often seen as challenging diagnostic lesions but the majority of them are easily classified. This article outlines the diagnostic features required for separating the most common of odontogenic cysts and select osseous lesions of the jaws. Clinical and radiographic findings of these jaw lesions often lead to a differential diagnosis that only the histologic findings will clarify. Dentigerous cyst, keratocystic odontogenic tumor, and certain ameloblastomas that have cystic change, may have identical radiographic findings, with only separation by their specific histologic features leading to the significantly different treatments required for each. Conversely, some cystic lesions can appear histologically identical and cannot be diagnosed without the radiographic findings. Certain osseous lesions of the jaws are particularly problematic for diagnosis without the appropriate radiographic findings, and the diagnosis should probably not be attempted on the histologic findings alone. This article will integrate the necessary clinical, radiographic, and histologic findings required to address the most common odontogenic lesions.

Background Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but potentially serious, adverse event that can occur after exposure to bone-modifying agents (BMAs; e.g., bisphosphonates, denosumab, and antiangiogenic therapies). BMAs are typically used at higher doses to prevent skeletal-related events in cancer patients and at lower doses for osteoporosis/bone loss. MRONJ can cause significant pain, reduce quality of life, and can be difficult to treat, requiring a multiprofessional approach to care. Methods We reviewed the literature and guidelines to summarize a practical guide on MRONJ for nurses and other allied healthcare professionals. Results While there is a risk of MRONJ with BMAs, this should be considered in relation to the benefits of treatment. Nurses and other allied healthcare professionals can play a key role alongside physicians and dentists in assessing MRONJ risk, identifying MRONJ, counseling the patient on the benefit–risk of BMA treatment, preventing MRONJ, and managing the care pathway of these patients. Assessing patients for MRONJ risk factors before starting BMA treatment can guide preventative measures to reduce the risk of MRONJ. Nurses can play a pivotal role in facilitating multiprofessional management of MRONJ by communicating with patients to ensure compliance with preventative measures, and with patients’ physicians and dentists to ensure early detection and referral for prompt treatment of MRONJ. Conclusions This review summarizes current evidence on MRONJ and provides practical guidance for nurses, from before BMA treatment is started through to approaches that can be taken to prevent and manage MRONJ in patients receiving BMAs.

A novel classification system, termed the Sivan classification, was developed to enhance the diagnosis of jaw lesions by utilizing visual volumetric analysis of three-dimensional Cone Beam Computed Tomography (CBCT) images. This classification groups lesions into ten categories, primarily divided into hypovolumetric, hypervolumetric, and normovolumetric groups. To validate this system, 10 raters—comprising 5 general dentists and 5 oral radiology specialists—assessed the CBCT images and diagnosed the lesions using the Sivan classification. Eight raters repeated the process after one month to assess consistency. The overall agreement between raters, quantified using kappa statistics, was 0.82, indicating excellent consistency. Hypervolumetric and normovolumetric lesions demonstrated the highest agreement (kappa 0.84 and 0.82, respectively), while hypovolumetric lesions showed substantial agreement (kappa 0.77). Pairwise interrater agreement ranged from 76 to 93%, with kappa values between 0.75 and 0.87. Intrarater reliability was equally strong, with kappa values between 0.79 and 0.89.These results suggest that the Sivan classification provides a robust and reliable framework for diagnosing jaw lesions using CBCT volumetric analysis, surpassing traditional diagnostic methods in accuracy and consistency.

Medication-related osteonecrosis of the jaw (MRONJ) has become a well-known side effect of antiresorptive, and antiangiogenic drugs commonly used in cancer management. Despite a considerable amount of literature addressing MRONJ, it is still widely accepted that the underlying pathomechanism of MRONJ is unclear. However, several clinical and preclinical studies indicate that infection seems to have a major role in the pathogenesis of MRONJ. Although there is no conclusive evidence for the infection hypothesis yet, available data have shown a robust association between local infection and MRONJ development. This observation is very critical in order to implement policies to reduce the risk of MRONJ in patients under antiresorptive drugs. This critical review was conducted to collect the most reliable evidence regarding the link between local infection and MRONJ pathogenesis.

SummaryPre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication.IntroductionThis study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses of this agent.MethodsData were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses.ResultsA total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04). There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not.ConclusionsThese findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ.