Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan.

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

Association Between Treated Periodontal Disease and Febrile Neutropenia in Perioperative Chemotherapy for Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: This study aimed to examine whether the incidence of febrile neutropenia (FN) during perioperative chemotherapy for breast cancer increased in patients with periodontal disease who had received prior dental treatment. METHODS: This retrospective cohort study conducted at a single tertiary care center included patients diagnosed with clinical stages I-III of breast cancer and had started neoadjuvant or adjuvant intravenous chemotherapy between July 2015 and November 2021. The exposure was periodontal disease (probing depth ≥6 mm) diagnosed by dentists before the start of chemotherapy. Almost all the patients received dental treatment and oral care before initiating chemotherapy. The primary outcome was FN incidence during chemotherapy. We used a multivariable logistic regression model adjusted for age, diabetes mellitus, chemotherapy regimen, and the mean relative dose intensity. RESULTS: Based on the eligibility criteria of this study, 141 women were included. The incidence of FN in the periodontal group (probing depth ≥6 mm) and control group (probing depth <6 mm) was 36.4% and 25.9%, respectively. The crude odds ratio (OR) for FN incidence was 1.63 (95% confidence interval [CI], 0.71-3.74; P = 0.24), and the adjusted OR was 1.52 (95% CI, 0.62-3.73; P = 0.36).  Conclusions: Occurrence of FN during perioperative chemotherapy for breast cancer is not a concern in patients undergoing dental treatment for periodontal disease before or during chemotherapy.

Direct Synthesis of Chalcones from Anilides with Phenyl Vinyl Ketones by Oxidative Coupling Through C-H Bond Activation.

A novel approach for synthesizing chalcones by Pd-catalyzed oxidative coupling is described. This is the first report of the efficient coupling reaction of acetanilides with phenyl vinyl ketones under mild conditions. Selective C-H activation occurred next to the acetamide group to afford 2-aminochalcone derivatives. The reaction proceeded under an O2 atmosphere without any chemical co-oxidants.

Synthesis of 3-acylindoles by oxidative rearrangement of 2-aminochalcones using a hypervalent iodine reagent and cyclization sequence.

An efficient one-pot method was developed for the construction of 3-acylindoles via oxidative rearrangement of 2-aminochalcones followed by intramolecular cyclization. The reaction was used to convert a variety of 2-aminochalcones into 3-acylindoles in moderate to high yields.

Dental trauma related to general anesthesia: should the anesthesiologist perform a preanesthetic dental evaluation?

Perioperative dental damage is one of the most common anesthesia-related adverse events and is responsible for the greatest number of malpractice claims against anesthesiologists; therefore, several dental considerations are warranted. A thorough evaluation may necessitate a dentist's help, requires that anesthesiologists receive more formal training regarding oral and dental anatomy, and enables performing the treatments necessary to minimize the risks of dental injuries. Nevertheless, this preanesthetic assessment is frequently overlooked by surgeons and anesthesiologists. The present study aimed to investigate, for both dentists and anesthesiologists, how often and under what circumstances dental trauma occurs during general anesthesia as well as isolate possible anatomical, dental, and anesthesiological risk factors, based on which suggestions for preventive measures could be made. Anesthesiologists must perform a thorough preoperative oral evaluation to help identify the dentition at risk; the evaluation should include the patient's dental history, oral/dental examination, and a specific discussion with the patient about any existing dentures or crowns. The dental examination should especially include an assessment of the patient's upper incisors--the teeth most likely to be injured during the perioperative period--for pre-existing damage. Preoperative notes should record any damages or missing teeth. In addition, anesthesiologists must take adequate intraprocedure precautions to prevent/minimize iatrogenic dental injury.

Pluripotency of mesenchymal cells derived from synovial fluid in patients with temporomandibular joint disorder.

AIMS: Mesenchymal stem cells are an interesting source of material for regenerative medicine. The present study aimed at characterizing the phenotype and differentiation potential of adherent synovial fluid-derived cells from temporomandibular joint (TMJ) disorder patients. MAIN METHODS: Synovial fluid collection takes place during TMJ cavity irrigation arthrocentesis under local anesthesia. The synovial fluid-derived adherent cells were fibroblast-like and spindle-shaped. Ex vivo-expanded synovial fluid-derived cells were shown to express STRO-1 and CD146, previously found to be present in bone marrow mesenchymal stem cells. Further, they were identified as being capable of differentiating into a variety of cell types including osteoblasts, chondrocytes, adipocytes, and neurons. KEY FINDINGS: The present study demonstrates that human pluripotent cells can be isolated from synovial fluid. These synovial fluid-derived cells cannot only be derived from a very accessible resource, but are also capable of providing sufficient cells for potential clinical applications. SIGNIFICANCE: These cells may play a role in the regenerative response during arthritic diseases and are promising candidates for developing novel cell-based therapeutic approaches for postnatal skeletal tissue repair.

Increased risk of temporomandibular joint closed lock: a case-control study of ANKH polymorphisms.

OBJECTIVES: This study aimed to carry out a histological examination of the temporomandibular joint (TMJ) in ank mutant mice and to identify polymorphisms of the human ANKH gene in order to establish the relationship between the type of temporomandibular disorders (TMD) and ANKH polymorphisms. MATERIALS AND METHODS: Specimens from the TMJ of ank mutant and wild-type mice were inspected with a haematoxylin and eosin staining method. A sample of 55 TMD patients were selected. Each was examined with standard clinical procedures and genotyping techniques. RESULTS: The major histological finding in ank mutant mice was joint space narrowing. Within TMD patients, closed lock was more prevalent among ANKH-OR homozygotes (p = 0.011, OR = 7.7, 95% CI 1.6-36.5) and the elder (p = 0.005, OR = 2.4, 95% CI 1.3-4.3). CONCLUSIONS: Fibrous ankylosis was identified in the TMJ of ank mutant mice. In the human sample, ANKH-OR polymorphism was found to be a genetic marker associated with TMJ closed lock. Future investigations correlating genetic polymorphism to TMD are indicated.

Prognostic factors in arthrocentesis of the temporomandibular joint: Comparison of bradykinin, leukotriene B4, prostaglandin E2, and substance P level in synovial fluid between successful and unsuccessful cases.

PURPOSE: To compare levels of bradykinin (BK), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and substance P (SP) between successful and unsuccessful cases of arthrocentesis of temporomandibular joint disorders (TMDs). PATIENTS AND METHODS: A total of 66 joints in 66 patients with TMDs who underwent arthrocentesis were evaluated in this study. Synovial fluid diluted with saline solution was aspirated from the superior joint compartment before arthrocentesis and their concentrations of BK, LTB4, PGE2, and SP were determined by enzyme-linked immunosorbent assay. The differences in the detection rate and concentration of each mediator between successful cases and unsuccessful cases of arthrocentesis were analyzed statistically. RESULTS: Arthrocentesis was successful for 77% (51/66) of the joints. The mean detection rate of LTB4 was significantly (P < .05) higher in the unsuccessful cases (47%) than in the successful cases (16%). The mean concentration of BK was significantly (P < .0005) higher in the unsuccessful cases (425 pg/mL) than in the successful cases (144 pg/mL). There was also a statistical correlation between the detection of LTB4 and PGE2 (P < .01). CONCLUSIONS: Increased levels of BK and LTB4 in the synovial fluid of patients with TMDs may indicate that arthrocentesis is less likely to be a successful treatment.

Specific expression of substance P in synovial tissues of patients with symptomatic, non-reducing internal derangement of the temporomandibular joint: comparison with clinical findings.

Our aim was to find out the extent of expression of substance P in synovial tissue from the human temporomandibular joints (TMJ) with symptomatic, non-reducing internal derangement, and to investigate the relationship between substance P and clinical findings. Fifty-four joints in 54 patients were examined immunohistochemically. Specimens of synovial tissue from 10 joints in 8 subjects with habitual dislocation of the TMJ with no pain were examined as controls. Cells that stained for substance P were found mainly among the endothelial cells in the blood vessels beneath the lining cells in synovial tissues from 47 of the 54 joints (87%) with internal derangement and from 5 of the 10 control joints. The extent score of cells that stained for substance P in joints with internal derangement was significantly higher than that in controls (p=0.02). The extent score of these cells did not correlate with pain in the joint or the degree of synovitis. These results suggest that substance P may have some roles in both the physiological and pathological conditions in patients with symptomatic internal derangement of the TMJ.

Anchored disc phenomenon with a normally positioned disc in the temporomandibular joint: characteristics and behaviour.

We aimed to elucidate the pathogenesis and evaluate the therapeutic behaviour of patients with an anchored disc phenomenon but a normally positioned disc of the temporomandibular joint (TMJ). Fourteen patients with internal derangement including closed lock of one TMJ were examined. All had normally positioned discs. Synovial fluid was collected from the TMJ by arthrocentesis. Their symptoms, and the protein concentration in the synovial fluid, were evaluated. Their median duration of illness was 3 months (range 0.5-12), and the median protein concentration was low (343 microg/ml; range 36-791). Arthrocentesis was successful in nine. Arthroscopic findings in the five unsuccessful cases showed severe intra-articular adhesions of the TMJ. The main intra-articular pathological feature was the presence of adhesions, which might be affected by low protein concentrations in the synovial fluid. These findings may provide a new treatment in patients with normally positioned discs, despite the small number studied.

Electrophoretic separation of the synovial fluid proteins in patients with temporomandibular joint disorders.

OBJECTIVE: The present study was performed to characterize the patterns of protein expression in the synovial fluid (SF) of patients with temporomandibular joint disorders (TMD) by electrophoretic fractionation. STUDY DESIGN: Samples of the SF of 26 consecutive patients consisting of 16 with closed locking (CL group) and 10 with osteoarthritis (OA group), as well as 7 asymptomatic control subjects (AS group), were analyzed in the present study. SF samples were obtained from the upper compartment of the temporomandibular joint (TMJ) and equal quantities of SF protein were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The mean total protein concentrations in the SF from both of the TMD groups were higher than that in the AS group (1353 microg/mL in the CL group and 2485 microg/mL in the OA group vs 615 microg/mL in the AS group; P < .01). Moreover, the mean total SF protein concentration was higher in the OA group than in the CL group (P < .01). There was a correlation between the total protein concentration in the SF from both patient groups and the degree of expanded joint effusion (P = .003, r = 0.685). Approximately 22 different protein bands with molecular weights ranging from 14 to 700 kd were clearly discernible on electrophoresis. The relative amounts of specific proteins in the SF of the TMD group were also different from those in the AS group (P < .05). The major difference in total protein concentration appeared to be due to the increased abundance of relatively high molecular weight proteins (>140 kd) in the TMD patients as compared to the AS group. CONCLUSIONS: The SF of patients with TMD showed significant quantitative differences in total protein abundance as compared to healthy subjects. Moreover, this protein abundance was correlated strongly with the degree of expanded joint effusion. The major difference in total protein concentration appeared to be due to the increased abundance of relatively high molecular weight polypeptides in the TMD patients as compared to the healthy control subjects. These observations of changes in the pattern of protein expression may help in understanding the etiological factors involved in the pathophysiology of TMD.

Anatomical study of the complications of intraoral vertico-sagittal ramus osteotomy.

PURPOSE: The present study was performed to determine the variations in anatomical features of the ramus and the course of the maxillary artery to reduce the risk of injury during intraoral vertico-sagittal ramus osteotomy (IVSRO). MATERIALS AND METHODS: The locations and sizes of anatomical features of the medial aspect of mandibular rami were measured in 94 bilateral sides of 47 dry mandibles as a control group, and the results were compared with 3-dimensional computed tomography images of 44 sides of 22 patients with prognathism. We also dissected 12 sides of 6 mandibles from cadavers in a simulated IVSRO procedure to determine the course of the maxillary artery near the medial aspect of the ramus. RESULTS: In the dry mandibles and patients with prognathism, the mandibular foramen was located slightly posterior to the center of the width of the mandibular ramus, and the lingula tip was located about one third the distance from the sigmoid notch to the inferior border of the ramus. The distance from the lateral margin of the mandibular foramen to the lateral surface of the mandibular ramus ranged from 3.1 to 4.4 mm. However, these distances showed various ranges. In the mandibles from Asian cadavers, the maxillary artery approached close to the ramus and passed lateral to the lower head of the lateral pterygoid muscle. CONCLUSIONS: The position of the mandibular foramen in rami varies among individuals and, therefore, should be confirmed preoperatively on axial CT images. In addition, the maxillary artery approaches close to the medial aspect of the sigmoid notch in many cases. Therefore, the medial aspect from the sigmoid notch should be exposed carefully in the IVSRO procedure to avoid damaging the maxillary artery.

Expression of capsaicin receptor TRPV-1 in synovial tissues of patients with symptomatic internal derangement of the temporomandibular joint and joint pain.

OBJECTIVE: To elucidate expression of capsaicin receptor TRPV-1 in synovial tissues of the human temporomandibular joint (TMJ) with internal derangement and discuss its relationship with joint pain. STUDY DESIGN: Fifty-four TMJs in 54 patients were examined using an immunohistochemical technique. As controls, 10 TMJs with habitual dislocation without pain were also examined. RESULTS: TRPV-1 was expressed mainly in the blood vessels beneath the lining cells in synovial tissues from 31 of the 54 joints with internal derangement and from 8 of the 10 control joints. The extent score of TRPV-1-stained cells with internal derangement was not significantly higher than that of controls. The extent score of TRPV-1 showed no correlation with joint pain. CONCLUSIONS: TRPV-1 was detected in the region of the posterior disk attachment of synovial tissues from the TMJ in patients with internal derangement and controls. TRPV-1 may play a role in maintenance of the physiologic condition of the TMJ.

Levels of soluble cytokine factors in temporomandibular joint effusions seen on magnetic resonance images.

OBJECTIVE: To elucidate the correlations between joint effusion (JE) on T2-weighted magnetic resonance images (MRI) of the temporomandibular joint (TMJ) and the levels of various cytokine receptors, cytokine antagonists, and protein in the synovial fluid of patients with temporomandibular joint disorders (TMD). STUDY DESIGN: Fifty-five TMJs of 55 patients with TMD were scanned by MRI, and synovial fluid samples were obtained on the same day. The grade of JE was evaluated on a scale of 0 to 3: Grades 0 and 1 indicated absence, and grades 2 and 3 indicated the presence of JE. Correlations were evaluated between JE and the concentrations of soluble tumor necrosis factor receptors I and II (sTNFR-I and sTNFR-II, respectively), IL-6 soluble receptor (IL-6sR), IL-1 soluble receptor type II, and IL-1 receptor antagonist and protein in the synovial fluid of patients with TMD. RESULTS: The concentrations of sTNFR-I and protein in the group with JE (18 joints) were significantly higher than in the group without JE (37 joints). In addition, there were significant positive correlations between the grade of JE and the levels of sTNFR-I, sTNFR-II, and protein. CONCLUSIONS: sTNFRs and protein may play important roles in the pathogenesis of TMD. These mediators seem to influence the expression of JE, which may reflect synovial inflammation of the TMJ.

Histologic evaluation of temporomandibular arthritis induced by mild mechanical loading in rabbits.

BACKGROUND: We still lack knowledge of causative factors in arthritis related to temporomandibular disorders (TMD). The goal of the present study was to investigate whether applying a mechanical loading on the glenoid fossa can induce arthritis. METHODS: Coil springs were placed in 24 rabbits so as to exert a force of 100 g between the orbital edge and the antegonial notch. At 1, 2, 4 and 8 weeks after the surgery, six samples of the temporomandibular joint (TMJ) were removed for histologic examination. RESULTS: The results showed that mild synovitis began 1-2 weeks after the start of loading, and the degree of synovitis was significant at 4 weeks, and that morphologic changes occurred in the articular eminence and condyle, while type II collagen in the cartilage of the articular eminence degraded prior to that in the condyle. CONCLUSIONS: Our results revealed that mild, continuous mechanical loading to the glenoid fossa induces synovitis of the articular capsule, and induces organic changes of the articular cartilage without destroying these tissues.

Vascular endothelial growth factor concentrations in synovial fluids of patients with symptomatic internal derangement of the temporomandibular joint.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an inducer of angiogenesis and permeability of small blood vessels. We determined the concentrations of VEGF in synovial fluid of patients with symptomatic internal derangement of the temporomandibular joint (TMJ). METHODS: Diluted synovial fluid was collected by a pumping procedure from 22 TMJs of patients with internal derangement and 10 control TMJs. VEGF concentration was determined by an enzyme-linked immunosorbent assay. RESULTS: The VEGF was detected in 14 of the 22 joints (64%) of patients with internal derangement, at a mean concentration of 67 pg/ml, but in only one control joint (12.5 pg/ml) (P = 0.004 for the difference in concentration). There was a significant correlation between VEGF concentration and total protein concentration in the synovial fluid (P = 0.002). CONCLUSIONS: The increased concentration of VEGF in patients with symptomatic internal derangement suggests that this growth factor may be involved in the pathogenesis of this condition.

Analysis of tumor necrosis factor-alpha, interleukin-6, interleukin-1beta, soluble tumor necrosis factor receptors I and II, interleukin-6 soluble receptor, interleukin-1 soluble receptor type II, interleukin-1 receptor antagonist, and protein in the synovial fluid of patients with temporomandibular joint disorders.

OBJECTIVE: To measure the levels of various cytokines, cytokine receptors, and cytokine antagonists in the synovial fluid of patients with temporomandibular disorders (TMD) and to determine the correlations among these expression levels. STUDY DESIGN: Synovial fluid was obtained from 55 patients with TMD and from 5 asymptomatic healthy volunteers as controls. The concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta, soluble tumor necrosis factor receptors I and II (sTNFR-I and sTNFR-II), IL-6 soluble receptor (IL-6sR), IL-1 soluble receptor type II, and IL-1 receptor antagonist were determined by enzyme-linked immunosorbent assay. RESULTS: The concentrations of TNF-alpha, IL-6, IL-1beta, sTNFR-I, and sTNFR-II were significantly higher in the synovial fluid of patients than in controls (P < .05). TNF-alpha level was positively correlated with those of IL-6, sTNFR-I, and sTNFR-II. In particular, there was a highly significant positive correlation between sTNFR-I and sTNFR-II. CONCLUSION: TNF and sTNFRs in the synovial fluid of patients with TMD may be important in the pathogenesis of these disorders.

Comparison of the clinical outcomes of patients having sounds in the temporomandibular joint with skeletal mandibular deformities treated by vertico-sagittal ramus osteotomy or vertical ramus osteotomy.

OBJECTIVE: This article describes the effects of the intraoral vertico-sagittal ramus osteotomy (IVSRO) procedure on the jaw of patients with temporomandibular joint (TMJ) disorders. STUDY DESIGN: IVSRO was performed on 15 patients (30 sides) who had mandibular protrusion or asymmetry with TMJ dysfunction. IVRO was performed on another 15 patients (30 sides). All of the 30 patients had sounds in the TMJ uni- or bilaterally. The relative positions of the condyle and disc and the range of motion of the condyles were determined by magnetic resonance imaging (MRI) before and 12 months after the operations. RESULTS: Sounds such as clicking improved in 92% (24/26) of the joints in the IVSRO group, and in 83% (20/24) of the joints in the IVRO group 12 months after the operation. The positional relationship between the condyle and disc on the MR images improved in 82% (9/11) of the joints with reduction of the anterior disc displacement; in 60% (3/5) of the joints without reduction of the anterior disc displacement in the IVSRO group; in 75% (9/12) of the joints with reduction of the anterior disc displacement; and in 40% (2/5) of the joints without reduction of the anterior disc displacement in the IVRO group. Immediately after the operation, the condyle was displaced anterio-inferiorly in all joints in both groups, but gradually returned to close to the preoperative position. There were no significant differences between the 2 groups regarding the extent of shift of the condylar head at 2 weeks and 12 months after the operation. CONCLUSION: The clinical outcomes of the IVSRO procedure are similar to those of the IVRO procedure. Therefore, IVSRO may be a suitable procedure for patients having TMJ dysfunction with skeletal mandibular deformities, particularly when an IVRO is unsuitable.

Relationship of calcitonin gene-related peptide in synovial tissues and temporomandibular joint pain in humans.

OBJECTIVE: To elucidate the expression of calcitonin gene-related peptide (CGRP) in synovial tissue taken from the human temporomandibular joint (TMJ) with internal derangement, and discuss the relationship between CGRP and joint pain. STUDY DESIGN: Using an immunohistochemical technique, 48 joints in 48 patients were examined. As controls, synovial tissue specimens from 7 joints with habitual dislocation without pain were also examined. RESULTS: In all of the internal derangement and control subjects, CGRP-positive cells were observed in the connective tissues around the blood vessels beneath the lining cells. The extent score of CGRP was significantly higher in the internal derangement group than in the control group (P=.033). There was a significant positive correlation between the extent score of CGRP and joint pain (P=.036, r=0.30). CONCLUSIONS: These results suggest that the expression of CGRP is increased in the synovial tissues from patients with internal derangement, and that CGRP seems to play an important role in the mechanism of pain production in patients with symptomatic internal derangement.