Takeshi Kaneuji

Risk Factors for Neurosensory Disturbance After Bilateral Sagittal Split Osteotomy Based on Position of Mandibular Canal and Morphology of Mandibular Angle

PURPOSE The aim of the present study was to evaluate the potential morphologic risk factors for postoperative neurosensory disturbance (NSD) after bilateral sagittal split osteotomy. PATIENTS AND METHODS The study subjects were 30 skeletal Class III patients (9 males and 21 females), with a mean age of 22.0 years (range, 16-39 years). All patients underwent bilateral sagittal split osteotomy for setback to correct mandibular prognathism. The bone marrow space between the outer mandibular canal and the lateral cortex of the ramus was measured on transaxial computed tomography images, and the length at the mandibular angle between the retromolar and gonion was measured on the lateral cephalograms. The NSD was tested bilaterally using discrimination to touch with the sharp head of a mechanical probe. Each patient was evaluated at 1, 3, and 6 months postoperatively. RESULTS The median bone marrow space was 1.96 mm (range, 0-4.5 mm), and median length of the mandibular angle was 30.93 mm (range, 23-37 mm). Neurosensory disturbance was present on 15 sides (25.0%) at 1 month postoperatively, 9 sides (15.0%) at 3 months postoperatively, and 7 sides (11.7%) at 6 months postoperatively. The difference in the incidence of NSD with a small bone marrow space and a long mandibular angle from that with a large bone marrow space and short mandibular angle was highly statistically significant (P = .006 and P < .01, respectively). CONCLUSIONS The frequency of NSD after bilateral sagittal split osteotomy in Class III cases was dependent not only on the position of mandibular canal, but also on the length of the mandibular angle. A lateral course of the mandibular canal and a long mandibular angle appeared to result in a high risk of injury to the inferior alveolar nerve, resulting in NSD owing to a compromised splitting procedure.

Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm(2)) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-κB ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of IκBα, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca(2+) pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca(2+) pathway.

Mechanisms involved in suppression of ADAMTS4 expression in synoviocytes by high molecular weight hyaluronic acid.

Aggrecan degradation is considered to play a key role in the progression of osteoarthritis (OA). Aggrecanases are members of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, and degrade aggrecan in OA cartilage. The aim of this study was to clarify the mechanisms of expression of ADAMTS4 induced by IL-1β in human fibroblast-like synoviocyte (HFLS) cells by high molecular weight hyaluronan (HMW-HA), a therapeutic agent used for OA. Monolayer cultures of HFLS cells were incubated with IL-1β and HMW-HA. In some experiments, cells were pretreated with the CD44 function-blocking monoclonal antibody or inhibitors of signaling pathways prior to addition of IL-1β and HMW-HA. The expressions of ADAMTS4 mRNA and protein were monitored using real-time RT-PCR, Western blotting, and immunofluorescence microscopy. To further determine the role of HMW-HA in IL-1β-induced ADAMTS4 expression, activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), Akt, and NF-κB were analyzed by Western blotting. HMW-HA suppressed ADAMTS4 mRNA and protein expressions induced by IL-1β. Pretreatment with the anti-CD44 monoclonal antibody recovered the inhibitory effect of HMW-HA on expression of ADAMTS4 mRNA induced by IL-1β. Western blotting analysis revealed that IL-1β-induced phosphorylation of p38 MAPK and JNK protein were diminished by HMW-HA. Furthermore, inhibition of the p38 MAPK and JNK pathways by chemical inhibitors suppressed ADAMTS4 mRNA expression stimulated by IL-1β. These results suggest that HMW-HA plays an important role as a regulatory factor in synovial tissue inflammation.

Dual effects of heparin on BMP-2-induced osteogenic activity in MC3T3-E1 cells

Heparin displays several types of biological activities by binding to various extracellular molecules, including pivotal roles in bone metabolism. We have previously reported that heparin competitively inhibits the binding activity of bone morphogenic protein-2 (BMP-2) to BMP and the BMP receptor (BMPR) and suppresses BMP-2 osteogenic activity. In the present study, we examined whether heparin affects osteoblast differentiation induced by BMP-2 at various time points in vitro. We found that 72 h of treatment with heparin inhibited alkaline phosphatase (ALP) activity. However, 144 h of treatment enhanced the ALP activity in BMP-2-stimulated MC3T3-E1 cells. Although heparin decreased the phosphorylation of Smad1/5/8 after 0.5 h of culture, prolonged periods of culture with heparin enhanced the Smad phosphorylation. In addition, 72 h of treatment with heparin enhanced the mRNA expression of runx2 and osterix in BMP-2-stimulated MC3T3-E1 cells. Furthermore, the mRNA expression of BMP antagonists and inhibitory Smads induced by BMP-2 was preferentially blocked by heparin at the 24 and 48 h time points. These findings indicate biphasic effects of heparin on BMP-2 activity and suggest that heparin has complex effects on the BMP-2 osteogenic bioactivities. Prolonged culture with heparin stimulated BMP-2-induced osteogenic activity via down-regulation of BMP-2 antagonists and inhibitory Smads.

Clinical comparison between the retromandibular approach for reduction and fixation and endoscope-assisted open reduction and internal fixation for mandibular condyle fractures.

Objective Endoscope-assisted transoral open reduction and internal fixation (EAORIF) for mandibular condyle fractures has recently become popular because it is minimally invasive, provides excellent visibility without a large incision, and reduces surgical scarring and the risk of facial nerve injury. This report describes a retrospective clinical study that compared certain clinical parameters, including postoperative function, between the retromandibular (RM) approach and EAORIF. Methods Fifteen patients were treated by the RM approach, whereas 15 underwent EAORIF between July 2006 and September 2011 at Kyushu Dental College, Japan. Clinical indices comprised fracture line, fracture type, number of plates used, surgical duration, bleeding amount, and functional items, including maximum interincisal opening, mandibular deviation on the opening pathway, malocclusion, facial paresthesia, and temporomandibular joint pain and clicking. Results The areas subjected to either approach included lower neck and subcondyle. The RM approach was used for mandibular condyle fractures with dislocation of a small bone segment. Both groups used 2 plates in all cases. Surgical duration, maximum interincisal opening, mandibular deviation, occlusion, and temporomandibular joint function at 6 months after surgery were comparable between groups. The average bleeding amount in the EAORIF group was greater than in the RM group. One patient from the RM group developed facial paresthesia that persisted for 6 months after surgery. Conclusions It was concluded that surgical treatment was suitable for fractures of the lower neck and subcondylar. Both procedures showed good results in the functional items of this study.

Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ.

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital. Patients and Methods: This single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlying risk factors, clinical features, location and bone marker levels of BRONJ. Results: The mean BRONJ remission rate was 57.6%, and the median duration of remission was seven months. Eighteen patients (34.6%) had persistent or progressive disease with a recommended conservative treatment for BRONJ. Notably, urinary cross-linked N-terminal telopeptide of type 1 collagen (NTX) levels in those resistant to conservative treatment tended to be lower than in patients that healed well. Conclusions: We confirm that a significant proportion of BRONJ sufferers are refractory to a recommended conservative treatment and find that anticancer drugs, periodontal disease, the level of bone exposure and the dosage of intravenous BPs (e.g. zoledronate) represent specific risk factors in BRONJ that may determine the success of a recommended conservative treatment. Additionally, the NTX levels might be able to be a prognostic factor for the conservative treatment of BRONJ; additional research is necessary. Key words:Bisphosphonate, osteonecrosis, jaw, prognostic, retrospective.

Self-activated mesh device using shape memory alloy for periosteal expansion osteogenesis

The present study evaluated the use of this self-activated shape memory alloy (SMA) device, with a focus on its effects in the region under the periosteum. Twelve Japanese white rabbits were used in this study. The device was inserted under the periosteum at the forehead. In the experimental group, the device was pushed, bent, and attached to the bone surface and fixed with a titanium screw. In control group, the device was only inserted under the periosteum. After 14 days, the screw was removed and the mesh was activated in the experimental group. Rabbits were sacrificed 5 and 8 weeks after the operation and newly formed bone was histologically and radiographically evaluated. The quantitative data by the area and the occupation of newly formed bone indicated that the experimental group had a higher volume of new bone than the control group at each consolidation period. Histologically, some newly formed bone was observed and most of the subperiosteal space underneath the device was filled with fibrous tissue, and a thin layer of immature bone was observed in the control group. In the experimental group, multiple dome-shaped bones, outlined by thin and scattered trabeculae, were clearly observed under the SMA mesh device. The use of self-activated devices for the periosteal expansion technique may make it possible to avoid donor site morbidity, trans-skin activation rods, any bone-cutting procedure, and the following intermittent activation procedure.

Mechanisms involved in inhibition of chondrogenesis by activin-A.

OBJECTIVES Activin-A, a member of the TGF-β family, is known to be present in bone and cartilage. Although, involvement of the TGF-β family in chondrogenesis has been reported, the mechanism by which activin-A regulates chondrogenesis has not been fully elucidated. The aim of this study was to investigate the effects of activin-A on chondrocyte differentiation in vitro. MATERIALS AND METHODS Monolayer cultures of mouse chondrocyte ATDC cells were pretreated with a variety of inhibitors of major signaling pathways prior to addition of activin-A. The expressions of sox9, runx2, and osterix mRNA were detected using real-time PCR. To determine chondrocyte differentiation, sulfated glycosaminoglycans were stained with Alcian blue. To further elucidate the role of activin-A on chondrogenesis regulation, phosphorylation of Smad2/3, ERK, JNK, and Akt proteins was determined by western blotting. RESULTS Activin-A suppressed the transcription of sox9, runx2, and osterix mRNA, as well as sulfated glycosaminoglycans accumulation. Activin-A also inhibited constitutive phosphorylation of JNK and Akt proteins. Furthermore, inhibition of the JNK and PI3K-Akt pathways by chemical inhibitors suppressed chondrogenesis in ATDC5 cells. CONCLUSIONS These results indicate that activin-A may suppress chondrocyte differentiation in ATDC5 cells via down-regulation of JNK and Akt phosphorylation.

Evaluation of mandibular reconstruction with particulate cancellous bone marrow and titanium mesh after mandibular resection due to tumor surgery.

There are numerous treatment modalities for mandibular defects after tumor surgery. Autogenous particulate cancellous bone marrow graft combined with titanium mesh (PCBM-MESH) is an alternative procedure. The purpose of this study was to evaluate PCBM-MESH for mandibular reconstruction. There were a total of 10 cases from 2000 to 2011. Mandibles were successfully reconstructed in 9 cases; however, reconstruction failed in 1 case. Overall, the recovery of facial contours was excellent; conversely, the evaluation of prosthetic treatment varied widely. Thus, we suggest 3 steps for mandibular reconstruction: (1) recover the continuity of bone segments; (2) simulate optimum facial contours and dental occlusion; and (3) perform the occlusion with dental prostheses. PCBM-MESH is a valuable method for mandibular defects—particularly for restoring facial contours and a favorable alveolar ridge.

Variety and complexity of fluorine-18-labelled fluoro-2-deoxy-d-glucose accumulations in the oral cavity of patients with oral cancers

OBJECTIVES To elucidate the points that require attention when interpreting fluorine-18-labelled fluoro-2-deoxy-d-glucose ((18)F-FDG)/positron emission tomography (PET) images by demonstration of (18)F-FDG accumulation in various areas of the oral cavity other than primary lesions in patients with oral cancers. METHODS (18)F-FDG accumulations with a maximal standardized uptake value of over 2.5 in various areas of the oral cavity other than primary lesions were identified in 82 patients with oral cancers. RESULTS (18)F-FDG/PET-positive areas, excluding primary tumours, included the front intrinsic muscles of the tongue (89.0%), upper and lower marginal parts of the orbicularis oris muscle (64.6%), sublingual glands, palatine tonsil, pharyngeal tonsil, and lingual tonsil. In addition, some areas in the jaws also showed accumulation. CONCLUSIONS In patients with oral cancers, areas of (18)F-FDG accumulation in the oral cavity should be precisely identified and appropriately diagnosed, because accumulations can be seen in areas other than the primary tumour.