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Identifying the species of shark responsible for a bite on humans is both complex and important for understanding and managing the shark risk. Depending on the species, tiny teeth may or may not be present in the symphyseal space at the junction of the upper and lower half-jaws. In the case of bites, these tiny teeth (if present) often leave specific marks that may enable species to be quickly and reliably distinguished. We first present the anatomo-morphological characteristics of the jaws of the three most traumatogenic species for humans which are the white, tiger, and bull sharks. The white shark has no symphyseal teeth, while the tiger and bull sharks do. On the basis of three confirmed real case studies involving those species, we then show that for the white shark, the wide symphyseal space between the first two teeth of each jaw usually leads to wounds including the presence of (quite) large flesh flaps, without any tooth imprint. Conversely, wounds following bites made by the tiger and bull sharks will generally leave characteristic small imprints of symphyseal teeth, especially in the case of incomplete or superficial bites. Although not systematic, this diagnostic approach provides fast, reliable, and clean results. The discrimination between two species with symphyseal teeth can then be made on the basis of complementary anatomic information such as jaw curvature and details linked to the anatomy of the teeth themselves, as well as the ecological context., (© 2024 American Academy of Forensic Sciences.)

Objectives: 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)., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects., Methods: Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation., Results: IL-10 induced expression of arginase 1, TGF-β1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups., Conclusions: IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects., (© 2023 Wiley Periodicals LLC.)

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma)., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions., Methods: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed., Results: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001)., Conclusions: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis. The aim of the present study was to compare the macrophage populations between the craniofacial and extracranial skeleton and to investigate the changes induced by zoledronate (Zol) application and surgical interventions., Materials and Methods: An in vivo experiment was performed. 120 wistar rats were randomized to 4 groups (G1, G2, G3, G4). G1 served as an untreated control group. G2 and G4 received Zol injections for 8 weeks. Afterwards, the right lower molar of the animals from G3 and G4 was extracted and the right tibia osteotomized followed by osteosynthesis. Tissue samples were taken from the extraction socket and the tibia fracture at fixed time points. Immunohistochemistry was conducted to determine the labeling indexes of CD68 + and CD163 + macrophages., Results: Comparing the mandible and the tibia, we observed a significantly higher number of macrophages and a heightened pro-inflammatory environment in the mandible compared to the tibia. Tooth extraction caused an increase of the overall number of macrophages and a shift toward a more pro-inflammatory microenvironment in the mandible. Zol application amplified this effect., Conclusion: Our results indicate fundamental immunological differences between the jaw bone and the tibia, which might be a reason for the unique predisposition for MRONJ in the jaw bones. The more pro-inflammatory environment after Zol application and tooth extraction might contribute to the pathogenesis of MRONJ. Targeting macrophages might represent an attractive strategy to prevent MRONJ and improve therapy. In addition, our results support the hypothesis of an anti-tumoral and anti-metastatic effect induced by BPs. However, further studies are needed to delineate the mechanisms and specify the contributions of the various macrophage phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Struckmeier, Wehrhan, Preidl, Mike, Mönch, Eilers, Ries, Trumet, Lutz, Geppert, Kesting and Weber.)

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This systematic review aimed to investigate the radiological features of lymphomas and leukaemias affecting the jaws., Methods: A systematic literature review was conducted using the electronic databases of PubMed, Web of Science and Scopus. Articles that contained sufficient radiographic examinations (periapical, panoramic or computed tomography images) for individual cases were included. Additionally, either immunohistochemical or molecular confirmation was required prior to inclusion. Three authors evaluated and described the image quality and radiological features., Results: From an initial 1079 articles screened, 129 cases were included, containing 88 tomographic, 76 panoramic and 26 periapical examinations. The quality of the majority of images was sufficient for evaluation. Diffuse large B-cell lymphoma, Burkitt lymphoma, leukemic infiltration, plasmablastic lymphoma and extranodal Natural killer (NK)/T-cell lymphoma, nasal type were the most common subtypes. Involved teeth presented with mobility in 37.2% of the cases and a provisional diagnosis of inflammatory/infectious dental disease was considered in 49.2% of cases. Computed tomography exams were available for 76% of the cases, with most presented with an osteolytic lesion with ill-defined borders. Periosteal reactions were uncommon., Conclusion: Lymphoma/leukaemia infiltrates of the jaw bones are usually of high-grade subtypes and rarely present with periosteal reactions., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Jaw cyst is the most common pathology in the oral and maxillofacial region. The management of the teeth involved in cystic lesions is highly controversial. However, if the teeth involved in the cystic lesion could be preserved with their pulp vitality, the life span of these teeth will be considerably lengthened to improve the masticatory function of these patients after surgery. The present retrospective study over 10 years; with 92 patients that had cystic lesions of the jaws aimed to evaluate the effect of marsupialization on the preservation of the vitality teeth involved in the cystic lesion before and after treatment taking., Material and Methods: clinical retrospective study between January 2013 and January 2022, included 92 patients with a cystic lesion of jaw treated by marsupialization were carried out. The clinical data were collected; the number of teeth involved in the cystic lesion, the vitality of these teeth before and after marsupialization, the number of teeth that have undergone root canal treatment, the number of cases of failure (teeth that were extracted during surgery to open the cystic lesion and teeth that were extracted after surgery) as well as the duration of treatment for each patient were assessed., Results: Of 92 patients, 54 were men and 38 women with ages ranged from 7 years to 62 years were enrolled in this study.380 teeth were involved in the cystic lesion of that 352 teeth were positive and 28 teeth were negative before marsupialization. 28 teeth underwent root canal treatment before surgery. After surgery, 338 teeth were positive and 42 were negative. Among the 42 negative teeth, 31 teeth failed (extracted) and 11 teeth recovered their vitality before the end of the treatment.321 teeth were saved and preserved their pulp vitality., Conclusion: The effect of marsupialization is good; it saves and preserves the vitality of the teeth involved in the cystic lesion and it reduces the cost of treatment for the patients., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Peripheral giant cell granuloma (PGCG) is a common reactive lesion of the gingiva and alveolar ridge. The lesion is characterized by several histopathological features and cellular cannibalism according to the recent literature. The aim of this study was to examine and analytically record the histopathological features of PGCG in an attempt to contribute to a better knowledge of the microscopic characteristics of this lesion. Methods: Archival sections from 54 cases of PGCG were examined and the histopathological features were recorded. Results: Cannibalistic type I multinucleated giant cells were found in all cases (100 %). Interstitial hemorrhage and hemosiderin deposits were seen in 92.6 % of the cases. In addition, granules of hemosiderin in type I multinucleated giant cells were occasionally observed. Type I multinucleated giant cells were found in intimate contact with vessels and within the lumen of vessels in 35.1% and 20.3 % of the cases, respectively. Bone was present in 31.5 % of the cases and was most often woven in combination with lamellar bone. Ulcerated (74.1 %) and hyperplastic mucosal lining epithelium (62.2 %) were most often observed. Chronic and both acute and chronic types of inflammatory infiltration and mild intensity of inflammatory infiltration were most often found. Conclusion: In addition to the common microscopic features the data showed that only type I multinucleated giant cells of PGCGs have cannibalistic behavior, were occasionally involved in phagocytosis of hemosiderin and sometimes entered the lumen of vessels with an as yet unknown mediated process. [ABSTRACT FROM AUTHOR]

The articulatory system comprises the temporomandibular joints (TMJs), intra-articular discs, mandibular/jaw muscles and occlusion. In the simplest terms, the TMJ is the articulation between the upper and lower jaws. The teeth form the contacts between the upper and lower jaws and the muscles are the motors that move the mandible. This system is unique in that the TMJs are paired; any stimulus that affects one joint or any other single part of the articulatory system can have a 'knock-on effect' in the rest of the system.It is important to have a good understanding of anatomy, not only to be able to differentiate between what is physiological and what is pathological, but also to understand the objectives of some treatment options. Sound knowledge of anatomy is essential and an appreciation of the anatomical features associated with the TMJ can serve as a foundation for understanding the clinical management of temporomandibular disorders.This article reviews the functional anatomical features of the articulatory system with a look at the clinical significance of this anatomy., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

Objectives: The objective of this study is to evaluate the relationship between the radiological features of periosteal reactions (PR) and histopathological features of the lesions., Methods: A total of 4605 CBCT images were evaluated and they were classified according to their radiological differential diagnosis. Images with pathologies were listed according to their histopathological examinations as cystic lesions, benign tumours, malignant tumours, fibro-osseous lesions and osteonecrosis, while images without pathologies were listed as traumas and others. All groups were reclassified as with or without the presence of detected PR., Results: Pathologies and traumas were detected in 1801 of 4605 patients. There were 3 PR in 1140 cystic lesions, 4 PR in 102 benign tumours, 16 PR in 43 malignant tumours, 67 PR in 156 osteonecrosis/osteomyelitis cases and 3 PR in 262 trauma cases. As a result of the chi-square test between groups, there was a significant relationship between histopathologic diagnoses and periosteal reaction patterns (p = 0.000)., Conclusions: Although there is a significant overlap between the patterns of PRs, PRs can be used to narrow the possibilities in the differential diagnosis. However, PRs alone are not sufficient variables for differential diagnosis in the absence of cortical bone destruction, localization, clinical and systemic findings., (© 2021. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

Introduction: This meta-analysis provides reliable data on the prevalence of unicystic ameloblastomas (UA's) among solid/multicystic ameloblastomas (SMA's), as well the ratio of their presence in the maxilla and mandible and in the tooth-bearing area versus the posterior regions of the mandible, including the third molar region and ascending ramus., Material and Methods: A systematic review and meta-analysis was performed according to PRISMA guideline using the strategy ((unicystic ameloblastoma) OR (((ameloblastoma) OR (solid ameloblastoma)) OR (multicystic ameloblastoma))) NOT ((((systematic review) OR (literature review)) OR (case report)) OR (Immunohistochemical))., Discussion: The study included 3856 SMA's and 1537 UA's, which amounted to 28.5% UA's. Of the 380 cases of UA from twelve articles that mentioned the involved jaws, 355 were in the mandible and 25 in the maxilla. The preponderance for the mandible is much higher than reports from previous studies of smaller series. Only five articles mentioned the location within the mandible. The vast majority was in the posterior area., Conclusion: The consequences for treatment were discussed, with an emphasis on the approach to unicystic lesions in the posterior part of the mandible for which a protocol is suggested., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Giant cell granuloma of the jaws are benign osteolytic lesions of the jaws. These lesions are genetically characterized by mutually exclusive somatic mutations at TRPV4, KRAS, and FGFR1, and a fourth molecular subgroup which is wild-type for the three mutations. Irrespective of the molecular background, giant cell granulomas show MAPK/ERK activation. However, it remains unclear if these mutations lead to differences in their molecular signaling in giant cell granulomas., Methods: Metabolomics, proteomics, and phosphoproteomics analyses were carried out in formalin-fixed paraffin-embedded samples of giant cell granuloma of the jaws. The study cohort consisted of five lesions harboring mutations in FGFR1, six in KRAS, five in TRPV4, and five that were wild-type for these mutations., Results: Lesions harboring KRAS or FGFR1 mutations showed overall similar proteomics and metabolomics profiles. In all four groups, metabolic pathways showed similarity in apoptosis, cell signaling, gene expression, cell differentiation, and erythrocyte activity. Lesions harboring TRPV4 mutations showed a greater number of enriched pathways related to tissue architecture. On the other hand, the wild-type group presented increased number of enriched pathways related to protein metabolism compared to the other groups., Conclusion: Despite some minor differences, our results revealed an overall similar molecular profile among the groups with different mutational profile at the metabolic, proteic, and phosphopeptidic levels., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: It is unclear whether certain bacteria initiate the development of inflammatory jaw conditions, or whether these diseases create a milieu for dysbiosis and secondary colonization of indigenous flora. At present, there are no comparative studies on the types of bacteria that colonize different inflammatory jaw conditions. Accordingly, this study aims to identify and compare the types of bacteria isolated in osteomyelitis, osteoradionecrosis, and MRONJ., Methods: This is a retrospective cohort study of patients diagnosed with inflammatory jaw conditions. The predictor variables were classification of bacteria as oral flora, categorized herein as resident bacteria, non-resident bacteria, or opportunistic organisms. The outcome variables were a diagnosis of osteomyelitis, osteoradionecrosis, and MRONJ. Covariates were age, sex, penicillin allergy, a diagnosis of diabetes and a history of smoking. Data analysis was performed using ANOVA and chi-squared tests., Results: A total of 105 patients with inflammatory jaw conditions were enrolled. The final sample size was 69 subjects of which 16 were diagnosed with osteomyelitis, 20 with osteoradionecrosis, and 33 with MRONJ. There was no difference in the frequency that resident bacteria were isolated. Non-resident bacteria, which included Staphylococcus and Enterococcus among others, were isolated more frequently at 75% in osteomyelitis compared to 60% in osteoradionecrosis and 48% in MRONJ cases. There is weak evidence of significant difference when comparing osteomyelitis and MRONJ cases (P = .08). Opportunistic organisms, which included Mycobacterium and Candida, were isolated more frequently in osteoradionecrosis at 30% compared to 12.5% in osteomyelitis and 12.12% in MRONJ cases. There is weak evidence of significant difference when comparing osteoradionecrosis and MRONJ cases (P = .1)., Conclusion: Non-resident bacteria including Staphylococcus and Enterococcus may be more frequently isolated in patients with osteomyelitis, while opportunistic organisms like Mycobacterium and Candida may be more frequently found in patients diagnosed with osteoradionecrosis., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Benign fibro-osseous lesions (BFOLs) are heterogeneous intraosseous disease processes sharing overlapping histopathologic features and demonstrate a wide range of biological behavior. The aim of this study is to highlight the importance of clinical and radiological findings for the definitive histopathologic diagnosis of benign fibro-osseous lesions of the jaws., Materials and Methods: This is a cross-sectional retrospective study evaluating the three main groups of BFOLs: Cemento-osseous dysplasia, ossifying fibromas, and fibrous dysplasia. Previously diagnosed BFOL cases were searched for thoroughly from the archives of Istanbul University, Institute of Oncology, Department of Tumor Pathology in between 2005 and 2015. Clinical and radiological data of these cases were identified and recorded. The histopathologic features were reevaluated from the H&E-stained slides., Results: A total of 276 BFOL cases were identified and reevaluated for the study. The most common BFOL type was cemento-osseous dysplasia (n = 135), followed by cemento-ossifying fibroma (n = 77), fibrous dysplasia (n = 53) and juvenile ossifying fibroma (n = 11). The female/male ratio was 3.4:1 with a strong predilection for the 4th decade (n = 102). The mandible (n = 209) was the predominantly affected jaw. Prominent osteoblastic rimming around the bony lesion was commonly observed for cemento-ossifying fibroma (n = 60/77), followed by cemento-osseous dysplasia (n = 23/135). Predominant ossification patterns showed some differences among the groups. The most common radiological feature was the mixed radiolucent/radiopaque internal structure., Conclusion: Our results document various clinical, radiological and histopathologic findings of BFOLs. Even some histopathologic differences are observed, clinical and radiographic correlation is mandatory prior to the definitive histopathologic diagnosis of BFOLs for the prevention of possible misdiagnoses or inappropriate treatments., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Hyperparathyroidism is one of the most common endocrine disorders worldwide. In countries where routine biochemical screening is not common, symptomatic hyperparathyroidism predominates. Its manifestations include skeletal alterations, calcification of soft tissues, kidney stones, and functional alterations in other systems. Notably, jaw alterations can be the first clinical sign of hyperparathyroidism, including brown tumor, renal osteodystrophy, osteitis fibrosa, and leontiasis ossea, and knowing such conditions is of core importance for the multidisciplinary diagnosis and management of hyperparathyroidism. We aimed to perform a concise review, systematizing the concepts and mechanisms underlying hyperparathyroidism and associated gnathic alterations. In addition, a detailed description of the clinical aspects of the jaw manifestations is presented., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We report the case of a 10-year-old child with bilateral mandibular localization of a central giant cell granuloma occurring in the setting of Noonan syndrome. The histological appearance was classic with two intermigled components, one fibrous with non-atypical mononuclear cells, the other consisting of numerous osteoclast-like giant cells. This aspect is similar to that observed in the brown tumor as well as that of cherubism, which can also give multiple bone lesions. We will discuss the other lesions to consider in case of benign giant cell bone lesions affecting the jawbones, sometimes multiple and part of which falls within the scope of RASopathies., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

(1) Background: Many radiolucent jaw lesions exist, and they often show a radiographic resemblance, rendering diagnosis a challenging act. Closely related lesions should be frequently mentioned together in the academic literature, which might be helpful for junior practitioners in determining their differential diagnosis. The usefulness of bibliometric analysis in this respect has yet to be demonstrated. (2) Methods: This study evaluated academic publications on radiolucent jaw lesions, as indexed by the Web of Science Core Collection database. The mentions of radiolucent jaw lesions were extracted from the complete bibliographic records of the publications, and co-word analyses were conducted with the aid of VOSviewer. (3) Results: Based on 1897 papers, visualization maps were synthesized to evaluate co-occurrences of the radiolucent jaw lesions. Ameloblastoma was frequently mentioned together with odontogenic keratocyst, dentigerous cyst, and radicular cyst. Osseous dysplasia was co-mentioned with osteomyelitis, ossifying fibroma, odontoma, fibrous dysplasia, and apical periodontitis. (4) Conclusions: The co-word analysis, a form of bibliometric analysis, could demonstrate a relatedness of radiolucent jaw lesions that could be considered at differential diagnosis.

Osteonecrosis of the jaws (ONJ) usually has a clear etiology. Local infection or trauma, radiotherapy and drugs that disrupt the vascular supply or bone turnover in the jaws are its major contributors. The thrombotic occlusion of the bone's venous outflow that occurs in individuals with hereditary thrombophilia and/or hypofibrinolysis has a less known impact on jaw health and healing capability. Our research provides the most comprehensive, up-to-date and systematized information on the prevalence and significance of hereditary thrombophilia and/or hypofibrinolysis states in ONJ. We found that hereditary prothrombotic abnormalities are common in patients with ONJ refractory to conventional medical and dental treatments. Thrombophilia traits usually coexist with hypofibrinolysis traits. We also found that frequently acquired prothrombotic abnormalities coexist with hereditary ones and enhance their negative effect on the bone. Therefore, we recommend a personalized therapeutic approach that addresses, in particular, the modifiable risk factors of ONJ. Patients will have clear benefits, as they will be relieved of persistent pain and repeated dental procedures.

Background: Malignant transformation of fibrous dysplasia (FD) is very rare and little is known about this occurrence., Methods: We present the detailed clinical course of three cases of osteosarcoma arising from FD of the jaws and explore the genetic aberrations by Sanger sequencing, whole-exome sequencing (WES) and immunohistochemistry (IHC). A literature review of important topics related to this occurrence was also performed., Results: It was observed that patients with secondary sarcoma from FD showed a wide range of ages, with most during the third decade. Female and males were equally affected. Craniofacial bones and femurs were the most affected sites. High-risk factors for this occurrence included polyostotic FD, McCune-Albright syndrome and excess growth hormone. Notably, a potential relationship between thyroid hormones and sarcoma development was suggested in one patient, who began to show malignant features after hypothyroidism correction. Sanger sequencing revealed GNAS mutations of FD retained in all malignant tissues. Additionally, abnormal TP53 was demonstrated in all three cases by WES and IHC. WES also revealed two other driver mutations, ROS1 and CHD8, and large amounts of somatic copy number alterations (CNAs) where various oncogenes and tumour suppressors are located., Conclusion: This study demonstrated and reviewed the clinical features and risk factors for a rare occurrence, secondary sarcoma from FD, and provided important new knowledge about its genetics., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The objective of this study was to find out if suppression of NF-kB complex function by p65-TMD-linked PTD could reduce host inflammation and bone resorption at peri-implantitis sites in rats. Twenty-one male 5-week-old SD rats were divided into three groups: untreated control group (A), silk-induced peri-implantitis group (B), and nt (nucleus transducible)-p65-TMD-treated, silk-induced peri-implantitis group (C). Implant sulcus of a rat in group C were divided into two groups, namely group Cp and Cb. Palatal implant sulcus where nt-p65-TMD solution was applied with an insulin syringe were assigned to group Cp. Buccal implant sulcus without topical nt-p65-TMD application were assigned to group Cb. H&E staining, TRAP staining, and immunohistological staining were done. The crestal bone levels of group A were significantly higher than those of group B at p<0.01. The crestal bone levels of group Cp were significantly higher than those of group Cb at p<0.05. H-E staining showed increased apical migration of junctional epithelium and inflammatory cells in group Cb. TRAP staining revealed more multinucleated osteoclasts in group Cb. As for immunohistological staining, group Cb showed many IL-6-positive cells while group Cp had none. In this study, p65-TMD-linked PTD inhibited NF-kB functions and reduced inflammation and bone resorption at peri-implantitis sites in rats., (© 2021. The Author(s).)

This study aimed to evaluate the bone regeneration capacity of a customized alloplastic material and xenograft with recombinant human bone morphogenetic protein-2 (rhBMP-2). We prepared hydroxyapatite (HA)/tricalcium phosphate (TCP) pure ceramic bone blocks made using a 3D printing system and added rhBMP-2 to both materials. In eight beagle dogs, a total of 32 defects were created on the lower jaws. The defective sites of the negative control group were left untreated (N group; 8 defects), and those in the positive control group were filled with particle-type Bio-Oss (P group; 12 defects). The defect sites in the experimental group were filled with 3D-printed synthetic bone blocks (3D group; 12 defects). Radiographic and histological evaluations were performed after healing periods of 6 and 12 weeks and showed no significant difference in new bone formation and total bone between the P and 3D groups. The 3D-printed custom HA/TCP graft with rhBMP-2 showed bone regeneration effects similar to that of particulate Bio-Oss with rhBMP-2. Through further study and development, the application of 3D-printed customized alloplastic grafts will be extended to various fields of bone regeneration.

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. Furthermore, the effect of tooth extraction during BMA therapy was analyzed after adjusting for confounding factors using the propensity score matching method. MRONJ occurred in 33 patients jaws. A longer duration of BMA administration, fewer number of teeth, presence of symptoms of local infection, and infected teeth were independent risk factors of MRONJ. However, tooth extraction during BMA therapy did not increase the risk. Propensity score matching analysis showed that tooth extraction significantly lowered the risk of MRONJ development. Teeth that can be an infection source increases the risk of MRONJ, and thus, they need to be extracted even during BMA administration., (© 2021. The Author(s).)

This study aimed to develop a high-performance deep learning algorithm to differentiate Stafne's bone cavity (SBC) from cysts and tumors of the jaw based on images acquired from various panoramic radiographic systems. Data sets included 176 Stafne's bone cavities and 282 odontogenic cysts and tumors of the mandible (98 dentigerous cysts, 91 odontogenic keratocysts, and 93 ameloblastomas) that required surgical removal. Panoramic radiographs were obtained using three different imaging systems. The trained model showed 99.25% accuracy, 98.08% sensitivity, and 100% specificity for SBC classification and resulted in one misclassified SBC case. The algorithm was approved to recognize the typical imaging features of SBC in panoramic radiography regardless of the imaging system when traced back with Grad-Cam and Guided Grad-Cam methods. The deep learning model for SBC differentiating from odontogenic cysts and tumors showed high performance with images obtained from multiple panoramic systems. The present algorithm is expected to be a useful tool for clinicians, as it diagnoses SBCs in panoramic radiography to prevent unnecessary examinations for patients. Additionally, it would provide support for clinicians to determine further examinations or referrals to surgeons for cases where even experts are unsure of diagnosis using panoramic radiography alone., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to compare the immunohistochemical expression of tenascin-C (Tn-C) regarding clinicopathological variables and its association with the clinical behavior of central giant cell lesions (CGCLs). Forty-eight paraffin-embedded samples of CGCLs were selected. Based on clinical and radiographic features, the lesions were classified as aggressive (A-CGCLs) and non-aggressive (NA-CGCLs) subtypes. Histological assessment included the microvessel count (MVC), multinucleated giant cell (MGC) count, and the proportion of tissue area involved by mononuclear stromal cells/interstitial fibrosis. Immunoreactivity, immunolocalization, and distribution patterns of Tn-C were studied immunohistochemically. The association between Tn-C expression and clinicopathological characteristics was analyzed separately and adjusted for confounders using logistic regression models. A significantly greater proportion of cases with moderate-to-intense, intracellular, and diffuse staining of Tn-C was observed in A-CGCLs. CGCLs with a size ≥3.3 cm, fast growth, cortical disruption, high MVC/MGC counts, and low interstitial fibrosis showed a significantly greater frequency of moderate-to-intense, intracellular, and diffuse staining. Logistic regression analysis indicated a strong/independent association of these three immunohistochemical parameters with the aggressiveness of lesions. These data appear to suggest a possible role for Tn-C in the etiopathogenesis of CGCLs of the jaws, where its upregulation might favor the destructive behavior of A-CGCLs.

Background: The aim of the present study was to evaluate the efficacy of pentoxifylline and tocopherol for the management of osteoradionecrosis of the jaws., Methods: Twenty-five patients diagnosed with osteoradionecrosis of the jaws treated with pentoxifylline 400 mg + tocopherol 400 mg three times daily (tid) were evaluated. Clinical records and image tests were reviewed. All patients were previously submitted to head and neck radiation therapy and presented with a clinical and radiographic diagnosis of osteoradionecrosis of the jaws., Results: Following therapy with pentoxifylline and tocopherol, 76% (19/25) of the patients showed complete mucosal healing, in which 47.3% (9/19) did not undergo sequestrectomy. From this particular group, 77.7% (7/9) were in stage I and 33.3% (3/9) used the protocol for up to 3 months. Among those who underwent to sequestrectomy, complete mucosal healing was observed in 52.7% (10/19). Among these, 60% (6/10) were in stage I and 100% of the patients were using the protocol for more than 3 months. In all other patients, partial healing of the mucosa was observed since they presented advanced disease. These represented 24% of the sample (6/25), 66.6% (4/6) were in stage III, and 60% (4/6) used the protocol for over 6 months., Conclusion: Pentoxifylline and tocopherol may provide effective management of osteoradionecrosis of the jaws, and the association with sequestrectomy may avoid major surgical procedures.

Dental-tissue-derived stem cells have been used for tissue engineering owing to their ease of isolation and efficacy in in vitro and in vivo proliferation and differentiation. Nanohydroxyapatite/chitosan/gelatin (nHA/CG) three-dimensional porous scaffolds are promising for bone tissue engineering, especially jaw bone regeneration, because of their structural and functional similarity to natural bone. In our previous study, the efficiency of scaffolds with stem cell complexes in osteogenesis was confirmed in vivo in immunocompromised mice. However, studies on the bone regeneration efficiency of stem cell-seeded nHA/CG scaffolds using large animal jaw bone defect models have not been conducted. This study evaluated the bone regeneration potential of the nHA/CG scaffolds with transplanted human periodontal ligament stem cells (hPDLSCs) in critical-sized jaw bone defects in minipigs. The hPDLSCs isolated from periodontal ligaments of discarded teeth (postorthodontic purposes) were seeded onto the nHA/CG scaffolds. The scaffold was successfully synthesized according to our previous studies. Forty-eight critical-sized jaw bone defects were created in 12 minipigs. The defects were randomly assigned to one of three groups [scaffolds with seeded hPDLSCs (hPDLSCs/nHA/CG), only scaffold (nHA/CG), and a negative control group, ie, no cells and scaffolds implanted into defects] to investigate jaw bone regeneration. The bone regeneration capacities of the three groups were assessed for up to 12 weeks. The results showed that the hPDLSCs adhered well to the nHA/CG scaffold in vitro, and the cell-nHA/CG composites significantly increased new bone formation and generated large bones with normal architectures and vascularization in vivo compared to the nHA/CG and control groups. Immunohistochemistry staining showed that runt-related transcription factor 2 (Runx2) was highly expressed in the bone marrow formed in the hPDLSCs/nHA/CG group. This study provides strong evidence for future clinical applications of the nHA/CG scaffolds transplanted with hPDLSCs to regenerate the bone in large jaw bone defects.

MicroRNAs (miRNAs or miRs) play important roles in osteoporosis and exhibit high potential in the therapeutic treatment of this condition. The present study aimed to explore the effects of miR‑146a on bone loss noted in the jawbones of ovariectomized (OVX) rats and the interaction of miR‑146a with the Wnt/β‑catenin signaling pathway. OVX Sprague‑Dawley female rats were used to establish the animal model of osteoporosis (OP). Bone mineral density (BMD) was measured via dual‑energy X‑ray and the miR‑146a levels were detected by reverse transcription‑quantitative PCR. miR‑146a antagonist (miR‑146a‑A) and negative control (miR‑146a‑NC) were used to examine the effects of miR‑146a on OVX rats. The contents of osteocalcin and tartrate resistant phosphatase (TRAP) were detected via ELISA. Hematoxylin and eosin, and TRAP staining were used to observe the pathological changes and the number of osteoclasts in the jawbone, respectively. In addition, the expression levels of the nuclear factor of activated T cells c1 (NFATc1), c‑Fos and cathepsin K (CTK) in the jawbone were detected by immunohistochemistry, whereas the expression levels of osteoprotegerin, TRAP, dickkopf1, Wnt2 and β‑catenin in the same tissues were assessed by western blot analysis. The Wnt2 activator (DKK2‑C2) and inhibitor (endostatin) were used to examine the effects of miR‑146a on the Wnt/β‑catenin pathway. The results indicated that the BMD was increased, whereas the contents of osteocalcin and TRAP were decreased in the miR‑146a‑A group compared with those noted in the OP or negative control groups (P&lt;0.05). Although the trabecular bone area of the OP group was decreased, the conditions were improved in the miR‑146a‑A group. The number of osteoclasts was decreased in the miR‑146a‑A group compared with that noted in the OP group (P&lt;0.05). The expression levels of NFATc1, c‑Fos and CTK in the miR‑146a‑A group were decreased compared with those noted in the OP or negative control groups (P&lt;0.05). Similar results were found following the comparison of the miR‑146a‑A group with the DKK2‑C2 group. Taken together, these data demonstrated that miR‑146a downregulation inhibited OP of the jawbone in OVX rats by activating the Wnt/β‑catenin signaling pathway.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect. There are multiple hypotheses to explain the development of MRONJ. Reduced bone remodeling and infection or inflammation are considered central to the pathogenesis of MRONJ. In recent years, increasing evidence has shown that bisphosphonates (BPs)-mediated immunity dysfunction is associated with the pathophysiology of MRONJ. In a healthy state, mucosal immunity provides the first line of protection against pathogens and oral mucosal immune cells defense against potentially invading pathogens by mediating the generation of protective immunoinflammatory responses. In addition, the immune system takes part in the process of bone remodeling and tissue repair. However, the treatment of BPs disturbs the mucosal and osteo immune homeostasis and thus impairs the body's ability to resist infection and repair from injury, thereby adding to the development of MRONJ. Here, we present the current knowledge about immunity dysfunction to shed light on the role of local immune disorder in the development of MRONJ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Gao, Ren, Li, Zheng, Li, Jiang, Yang and Zhi.)

The regulated expansion of chondrocytes within growth plates and joints ensures proper skeletal development through adulthood. Mutations in the transcription factor NKX3.2 underlie spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD), which is characterized by skeletal defects including scoliosis, large epiphyses, wide growth plates and supernumerary distal limb joints. Whereas nkx3.2 knockdown zebrafish and mouse Nkx3.2 mutants display embryonic lethal jaw joint fusions and skeletal reductions, respectively, they lack the skeletal overgrowth seen in SMMD patients. Here, we report adult viable nkx3.2 mutant zebrafish displaying cartilage overgrowth in place of a missing jaw joint, as well as severe dysmorphologies of the facial skeleton, skullcap and spine. In contrast, cartilage overgrowth and scoliosis are absent in rare viable nkx3.2 knockdown animals that lack jaw joints, supporting post-embryonic roles for Nkx3.2. Single-cell RNA-sequencing and in vivo validation reveal increased proliferation and upregulation of stress-induced pathways, including prostaglandin synthases, in mutant chondrocytes. By generating a zebrafish model for the skeletal overgrowth defects of SMMD, we reveal post-embryonic roles for Nkx3.2 in dampening proliferation and buffering the stress response in joint-associated chondrocytes., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Background: Odontological effects of ionizing radiation (IR) as a result of radiotherapy, the consequences of accidents at nuclear power plants and industry, individual occupational exposure, etc. deserve significant attention interns of radiation medicine and radiation safety., Objective: to analyze and summarize clinical and experimental data on the odontological radiation effects., Object: the pathological changes in the hard tissues of teeth, pulp, periodontium, mucousmembranes of the mouth and jaws due to exposure to IR., Method: search in the PubMed / MEDLINE, Google Scholarabstract medical and biological databases, scientific libraries of the relevant sources of scientific information., Results: Radiobiological effects of IR due to its direct and indirect action are manifested throughout the period ofodontogenesis and formation of the facial skeleton. Experimental and clinical data (in children and adults) indicatethe increased risk of dental caries, reduction of pain threshold and vascularization of tooth pulp along with its fibrosis and atrophy, periodontal dysfunction, which predispose to a high probability of tooth loss. Abnormalities in theactivity of osteoblasts and cementoblasts of dental periosteum and osteoblasts of alveolar process in combinationwith circulatory disorders due to endothelial cell death, hyalinization, thrombosis and vascular obliteration increasethe risk of jaw osteoradionecrosis. Children who have undergone a prenatal exposure to IR as a result of theChornobyl NPP accident have a premature change of teeth. Deterioration of periodontal tissues and early development of acute and complicated dental caries are typical for children and adults affected by the Chornobyl disaster., Conclusions: Summarized data on the effects of radiation exposure under different conditions on teeth primordia(i.e. immature teeth), their formation and eruption in experimental and clinical settings, as well as on the odontological radiation effects in adults are summarized. Condition of the teeth in the Chornobyl NPP accident survivorsis described. Understanding and taking into account the radiobiological odontological effects is necessary in thelight of planning, preparing, and conducting local radiation therapy and developing the standards of radiation safety and measures to protect professionals and the public in the event of possible radiation accidents at the nuclearpower plants and industry facilities., (D. E. Afanasyev, S. F. Liubarets.)

Background and Aim of the Work: Fibrous dysplasia is a fibro-osseous osteopathy in which the normal bone architecture is replaced by fibrous tissue and non-functional trabeculae-like osseous structures. In head and neck area monostotic or polyostotic lesions cause a progressively expanding destructive bone swelling producing cosmetic deformities and functional impairments. The aim of this article is to present a retrospective review of a clinical case series with pathologically confirmed jawbone fibrous dysplasia for over an 8-year-period., Material and Methods: Clinical presentation and radiographic features of fibrous dysplasia affecting the jawbone skeletal area, surgical procedures performed including the reconstructive methods employed and clinical outcomes were analysed for each patient., Results: Seven cases were classified as having monostotic fibrous dysplasia while the others four cases were classified as having polyostotic form. The mandible was most commonly involved. The most common presenting features included marked facial deformity, intraoral bulging, malocclusion and dental alterations. Aesthetic and/or functional impairments were the major indications for surgical treatment in all the patients of this series. Six patients underwent bone remodelling while in the remaining cases subtotal or total resection was performed. Bone reconstruction by means of autologous free bone grafts or revascularized free bone flaps was made in three cases., Conclusion: The choice of the tailored therapeutic approach should be evaluated according the patient's age, rate of growth, anatomic location, type of involvement and the presence or not of functional disturbances and cosmetic alterations. Surgery remains the best therapeutic option.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising alternative source of mesenchymal stem cells (MSCs) that are enormously attractive for clinical use. This study was designed to investigate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) and/or osteogenic media (OMD) on bone regeneration of hUC-MSCs seeded on nanohydroxyapatite/collagen/poly(l-lactide) (nHAC/PLA) in a rabbit model. The characteristics of stem cells were analyzed by plastic adherence, cell phenotype, and multilineage differentiation potential. Cell proliferation was examined using cell counting kit-8 assay. Osteogenic differentiation was evaluated by quantitative Ca 2+ concentration, PO 4 3- concentration, alkaline phosphatase (ALP) activity, osteocalcin (OCN) secretion, and mineralized matrix formation. Bone regeneration was investigated in jaw bone defect repair in rabbit by microcomputed tomography, fluorescent labeling, and hematoxylin and eosin staining. Except for initial stress response, OMD and OMD + rhBMP-7 inhibited the proliferation of hUC-MSCs seeded on nHAC/PLA; rhBMP-7 inhibited cell proliferation in the nonlogarithmic phase and attenuated the inhibitory effect of OMD on cell proliferation. The inhibitory effects of OMD, rhBMP-7, and OMD + rhBMP-7 on cell proliferation were ranked as OMD > OMD + rhBMP-7 > rhBMP-7. OMD, rhBMP-7, and OMD + rhBMP-7 promoted Ca 2+ concentration, PO 4 3- concentration, ALP activity, OCN secretion, and mineralized matrix formation of hUC-MSCs seeded on nHAC/PLA. The promoting effects of OMD, rhBMP-7, and OMD+rhBMP-7 on Ca 2+ concentration, PO 4 3- concentration, ALP activity, OCN secretion, and mineralized matrix formation were ranked as rhBMP-7 > OMD > OMD + rhBMP-7, OMD > OMD + rhBMP-7 > rhBMP-7, OMD > rhBMP-7 > OMD + rhBMP-7, rhBMP-7 > OMD + rhBMP-7 > OMD, and OMD > rhBMP-7 > OMD + rhBMP-7, respectively. In rabbit jaw bone defect repair, OMD, rhBMP-7, and OMD + rhBMP-7 enhanced bone regeneration of hUC-MSCs seeded on nHAC/PLA, but the largest bone mineral apposition rate and bone formation were presented in cultures with rhBMP-7. These findings suggested that the combined use of rhBMP-7 and OMD may have no ideal synergistic effect on bone regeneration of hUC-MSCs seeded on nHAC/PLA in rabbit jaw bone defect.

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option., Patients and Methods: In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life., Results: Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity., Conclusion: Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.

Purpose: We investigated the promoting effect of concentrated growth factor (CGF) fibrin on the repair of jaw bone defects., Patients and Methods: We designed a clinical trial composed of patients with jaw defects. Forty patients were divided into the test and control groups. CGF fibrin combined with Bio-Oss bone powder (Giestlich Pharma, Wolhusen, Switzerland) was used in the test group. Bio-Oss bone powder alone was used in the control group. The concentration of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β in the red blood cell (RBC) layer and CGF gel was measured. At different time points before and after surgery, the serum bone alkaline phosphatase (BAP), osteocalcin, and bone mineral density levels were measured. Regular examinations and computed tomography scans were also performed in the follow-up period., Results: The CGF fibrin available for clinical use was obtained by centrifugation. One day after preparation by centrifugation, the VEGF and TGF-β concentration in the CGF gel was 2.57-fold and 3.4-fold greater than the concentration in the RBC layer, respectively. The BAP and osteocalcin levels increased at 1 and 12 weeks postoperatively in both groups. Furthermore, the BAP and osteocalcin levels in the test group were significantly greater than those in the control group at 1 and 12 weeks postoperatively (P < .05 for all). The bone mineral density in the bone defect area of the test group was also significantly greater than that of the control group at 6 months postoperatively (P < .05). Evaluation of the regular radiographic scans revealed that the effects in the test group were better than those in the control group., Conclusions: CGF fibrin could promote new bone formation in jaw defects, with benefit to the healing of bone tissue and, thus, is a promising bone repair material., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the inhibitory effects of zoledronate (ZOL) on adipose-derived stem cells (ADSCs) into osteoblasts for repairing jaw necrosis., Methods: ADSCs were induced to differentiate into osteoblasts. The differentiation characteristics of osteoblasts was observed under inverted microscope by alizarin red staining. The transwell assay was performed to evaluate the migration of ADSCs co-cultured with osteoblasts and divided into ZOL group treated with ZOL and N-ZOL group without ZOL treatment. The differentiation and proliferation characteristics of ADSCs differentiated osteoblasts were observed respectively. The expression of CTSK (Cathepsin K) and FGFR3 (Fibroblast growth factor receptor 3) in osteoblasts were analyzed by immunofluorescence and western blot., Results: The differentiation degree and proliferation of ADSCs to osteoblasts in N-ZOL group were both higher than those in ZOL group. The migratory cell number in ADSCs differentiation in ZOL group was higher than that of N-ZOL group. The protein expression of CTSK and FGFR3 in ADSCs differentiated to osteoblasts in ZOL group was higher than that in N-ZOL group., Conclusion: The differentiation of ADSCs into osteoblasts is significantly inhibited by ZOL. Due to this reason, it may be difficult to achieve good results by ZOL induced ADSCs into osteoblasts in repairing jaw necrosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: This work was aimed to investigate the effect of microRNA-141 (miR-141) overexpression in the jawbones of ovariectomized-induced osteoporosis rats and investigate the role of miR-141 in the Wnt/β-catenin pathway., Methods: Twenty-four female rats were randomly divided into the sham group, ovariectomized osteoporosis group (OP), miR-141 agonist group (miR-141), and miR-141 scramble group (Scramble). Bone mineral density (BMD) and pathological changes of the jaw were detected. Serum receptor activator of nuclear factor-B ligand (RANKL), osteoprotegerin, tartrate-resistant acid phosphatase (TRAP), and bone gla protein (BGP) levels were tested by ELISA. The expression of Runt-related transcription factor 2 (Runx2), and Osterix measured by immunohistochemistry and the expression of Wnt, β-catenin, and Dickkopf1 (DKK1) proteins was measured by Western blot. Furhter, the Wnt agonist DKK2-C2, Wnt inhibitor Endostar were used to verify the effect of miR-141 overexpression on the Wnt/β-catenin pathway., Result: Compared with the OP group, the content of osteoprotegerin increased while the levels of RANKL, BGP, TRAP decreased in the miR-141 and DKK2-C2 groups (p < 0.05). The levels of Runx2 and Osterix increased significantly in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). Interestingly, the protein expression of Wnt and β-catenin increased while DKK1 was remarkably down-regulated in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). In contrast to the miR-141 group, the above results were reversed after treatment with the Endostar (p < 0.05)., Conclusion: Overexpression of miR-141 could inhibit the osteoporosis of jawbones in ovariectomized rats by activating the Wnt/β-catenin pathway., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)