Bone augmentation with alloplastic graft material in a patient under bisphosphonate therapy: A case report and literature review.

Cases of relatively safe dental implant treatment in patients with low-volume bisphosphonate (BP) have been gradually reported. Although bone augmentation is commonly used when the bone volume is insufficient for implant placement, the studies and case reports regarding the safety of bone augmentation in patients treated with BP remain insufficient. Herein, we report a case wherein bone augmentation was performed after BP treatment, with bone healing realized according to imaging, and we review the literature regarding BP and bone augmentation. A sixty-seven-year-old Japanese woman requested implant treatment for a hopeless lower right second molar. She had been taking minodronic acid hydrate (50 mg/4 wk) for 18 mo to treat steroid-induced osteoporosis. After obtaining informed consent, tooth extraction and bone augmentation within the extraction socket were performed. The tooth was extracted atraumatically to preserve the surrounding alveolar bone, and the extraction socket was intensely curetted. Subsequently, the socket was filled with carbonate apatite granules and covered with a biodegradable membrane, and the wound was sutured without tension. Although protracted wound healing without any symptoms of infection was observed, the wound healed completely. No clinical symptoms were observed, the color of the mucosa at the site was healthy, and imaging findings at a six month post-operation indicated that osteogenesis had progressed uneventfully.

Comparison of Skeletal Stability after Le Fort I Osteotomy With Bone Fixation Using Biodegradable and Titanium Systems: A Retrospective Study.

The titanium osteosynthesis system used for fixing bone segments after maxillary osteotomy provides reliable outcomes owing to its biocompatibility and adequate strength. In addition, several studies have evaluated the skeletal stability after maxillary osteotomy with fixation using a biodegradable system. However, the indications for applying a biodegradable system after maxillary osteotomy remain controversial. Therefore, this study aimed to compare the long-term skeletal stability of bone segments after maxillary osteotomy with bone fixation using biodegradable and titanium osteosynthesis systems and to assess the usefulness of a biodegradable osteosynthesis system. Patients who underwent Le Fort I osteotomy of the maxilla to correct jaw deformities between April 2008 and March 2021 were included in this study. A total of 45 patients were included, with 28 in the biodegradable osteosynthesis system group and 17 in the titanium group. Cephalometric and computed tomography analyses were performed to evaluate the skeletal stability of the bone segments after maxillary osteotomy with bone fixation using biodegradable or titanium osteosynthesis systems. The maxillary segment was repositioned anteriorly with a clockwise rotation. Skeletal stability was similar between the biodegradable and titanium osteosynthesis systems. Segmental changes occurred mainly in the first 6 months after surgery, and the segment was completely stable between 6 and 12 months after surgery. This study revealed no significant differences in skeletal stability after maxillary osteotomy between the biodegradable and titanium osteosynthesis systems. However, the findings in this study should be interpreted with caution owing to the small sample size and small amount of maxillary-segment movement.

Comparison of the skeletal stability after mandibular counter-clockwise rotation in three surgical procedures.

The treatment of mandibular deformities with an anterior open bite is challenging. In this study, skeletal stability after mandibular osteotomies was evaluated to determine the best treatment for mandibular prognathism with an anterior open bite in three procedures: intraoral vertical ramus osteotomy (IVRO), conventional sagittal split ramus osteotomy (conv-SSRO), and SSRO without bone fixation (nonfix-SSRO). Patients who underwent mandibular osteotomy to correct skeletal mandibular protrusion were included. Changes in skeletal and soft tissues were assessed using lateral cephalograms taken before (T1), 3 ± 2 days (T2), and 12 ± 3 months (T3) after surgery. Thirty-nine patients were included: nine in the IVRO group and 11 and 19 in the conv- and nonfix-SSRO groups, respectively. The mandibular plane angles (MPAs) of the T2-T1 were - 2.7 ± 2.0 (p = 0.0040), - 3.7 ± 1.7 (p < 0.0001), and - 2.3 ± 0.7 (p < 0.0001) in the IVRO, conv-SSRO, and nonfix-SSRO groups, respectively. The skeletal relapse of the MPAs was not related to the MPA at T2-T1, and it was approximately 1.3° in the conv-SSRO group. The skeletal relapse of the MAPs was significantly correlated with the MPA of T2-T1 in the IVRO (p = 0.0402) and non-fix-SSRO (p = 0.0173) groups. When the relapse of the MPAs was less than 1.3°, the MPA of T2-T1 was calculated as 2.5° in the nonfix-SSRO group. When the MPA of T2-T1 is less than 2.5°, non-fix SSRO may produce a reliable outcome, and when it is more than 2.5°, conv-SSRO may produce better outcomes.

Occlusal Plane Angle as a Key Factor for Chin Protrusion After Mandibular Osteotomy in Skeletal Class III.

There is no treatment algorithm to decide whether maxillomandibular or mandibular osteotomy alone should be performed in borderline cases. This study assessed the factors that affect the changes in soft tissue after mandibular setback. Patients who underwent mandibular osteotomy alone to correct mandibular protrusion were included in this study. Hard and soft tissue analyses were performed on lateral cephalograms before and 12±3 months after surgery. The popular points were set for referencing hard and soft tissues on the lateral cephalogram. Nasolabial, labiomental, and soft tissue facial plane angles were measured for the soft tissue assessment. To assess the mandibular setback amount, SNB was calculated. Twenty-one patients were included in this study. The nasolabial angle was increased after surgery and its change significantly correlated with the change in SNB ( P =0.00815). The change in soft tissue facial plane angle after surgery per change in SNB significantly correlated with the occlusal plane angle ( P =0.0009). An occlusal plane angle of at least 15.45 degrees was required for the SNB and soft tissue facial plane angle to change to the same degree. The occlusal plane angle (whether or not it was ≥15.45 degrees) may help in determining the surgical approach in borderline cases, specifically on whether maxillomandibular or mandibular osteotomy alone should be performed if the mandibular setback is simple.

Long-term effect of photodynamic therapy on oral squamous cell carcinoma and epithelial dysplasia.

BACKGROUND: Oral squamous cell carcinoma (OSCC) treatment consists mainly of surgery, chemotherapy, and radiotherapy, alone or in combination. Epithelial dysplasia (ED) is also treated with surgery. However, these treatments can induce functional and/or aesthetic disturbances. Photodynamic therapy (PDT) can preserve organs. Although short-term studies have shown good progress, long-term evaluations have not yet been conducted. This study aimed to clarify the long-term effects of PDT on OSCC and ED. METHODS: Patients who underwent PDT with the first (porfimer sodium) or second generation photosensitizers (talaporfin sodium) for early OSCC (T1 and T2) and ED were included in this study. The long-term prognosis was assessed. RESULTS: Twenty-three patients were included. Complete response (CR) was observed in 19 patients (82.6%) and partial response (PR) in 4 patients (17.4%) 4 weeks after PDT. Regarding long-term progress, local region recurrence occurred in 11 of 19 CR cases (57.9%), and the term of recurrence was 27.4 ± 30.4 months. Surgical resection was performed in all local recurrence and PR cases, and 3 patients died of the underlying disease. CONCLUSIONS: PDT provides a good outcome in the short term, but its long-term effects are limited.

Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation.

We have developed nanoballs, a biocompatible self-assembly nano-vector based on electrostatic interactions that arrange anionic macromolecules to polymeric nanomaterials to create nucleic acid carriers. Nanoballs exhibit low cytotoxicity and high transfection efficiently in vivo. This study investigated whether a gene-activated matrix (GAM) composed of nanoballs containing plasmid (p) DNAs encoding bone morphogenetic protein 4 (pBMP4) could promote bone augmentation with a small amount of DNA compared to that composed of naked pDNAs. We prepared nanoballs (BMP4-nanoballs) constructed with pBMP4 and dendrigraft poly-L-lysine (DGL, a cationic polymer) coated by γ-polyglutamic acid (γ-PGA; an anionic polymer), and determined their biological functions in vitro and in vivo. Next, GAMs were manufactured by mixing nanoballs with 2% atelocollagen and ß-tricalcium phosphate (ß-TCP) granules and lyophilizing them for bone augmentation. The GAMs were then transplanted to rat cranial bone surfaces under the periosteum. From the initial stage, infiltrated macrophages and mesenchymal progenitor cells took up the nanoballs, and their anti-inflammatory and osteoblastic differentiations were promoted over time. Subsequently, bone augmentation was clearly recognized for up to 8 weeks in transplanted GAMs containing BMP4-nanoballs. Notably, only 1 µg of BMP4-nanoballs induced a sufficient volume of new bone, while 1000 µg of naked pDNAs were required to induce the same level of bone augmentation. These data suggest that applying this anionic vector to the appropriate matrices can facilitate GAM-based bone engineering.

Gene-activated matrix harboring a miR20a-expressing plasmid promotes rat cranial bone augmentation.

Gene-activated matrix (GAM) has a potential usefulness in bone engineering as an alternate strategy for the lasting release of osteogenic proteins but efficient methods to generate non-viral GAM remain to be established. In this study, we investigated whether an atelocollagen-based GAM containing naked-plasmid (p) DNAs encoding microRNA (miR) 20a, which may promote osteogenesis in vivo via multiple pathways associated with the osteogenic differentiation of mesenchymal stem/progenitor cells (MSCs), facilitates rat cranial bone augmentation. First, we confirmed the osteoblastic differentiation functions of generated pDNA encoding miR20a (pmiR20a) in vitro, and its transfection regulated the expression of several of target genes, such as Bambi1 and PPARγ, in rat bone marrow MSCs and induced the increased expression of BMP4. Then, when GAMs fabricated by mixing 100 µl of 2% bovine atelocollagen, 20 mg ß-TCP granules and 0.5 mg (3.3 µg/µl) AcGFP plasmid-vectors encoding miR20a were transplanted to rat cranial bone surface, the promoted vertical bone augmentation was clearly recognized up to 8 weeks after transplantation, as were upregulation of VEGFs and BMP4 expressions at the early stages of transplantation. Thus, GAM-based miR delivery may provide an alternative non-viral approach by improving transgene efficacy via a small sequence that can regulate the multiple pathways.

KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1.

Kelch repeat and BTB domain-containing protein 11 (KBTBD11) is a member of the KBTBD subfamily of proteins that possess a BTB domain and Kelch repeats. Despite the presence of the Kbtbd11 gene in mammalian genomes, there are few reports about KBTBD11 at present. In this study, we identified the novel protein KBTBD11 as a negative regulator of osteoclast differentiation. We found that expression of KBTBD11 increased during osteoclastogenesis. Small-interfering-RNA-mediated knockdown of KBTBD11 enhanced osteoclast formation, and markedly increased the expression of several osteoclast marker genes compared with control cells. Conversely, KBTBD11 overexpression impaired osteoclast differentiation, and decreased the expression of osteoclast marker genes. Among six major signaling pathways regulating osteoclast differentiation, KBTBD11 predominantly influenced the nuclear factor of activated T cell cytoplasmic-1 (NFATc1) pathway. Mechanistically, KBTBD11 was found to interact with an E3 ubiquitin ligase, Cullin3. Further experiments involving immunoprecipitation and treatment with MG132, a proteasome inhibitor, showed that the KBTBD11-Cullin3 promotes ubiquitination and degradation of NFATc1 by the proteasome. Considering that NFATc1 is an essential factor for osteoclast differentiation, the KBTBD11 and Cullin3 probably regulate the levels of NFATc1 through the ubiquitin-proteasome degradation system. Thus, KBTBD11 negatively modulates osteoclast differentiation by controlling Cullin3-mediated ubiquitination of NFATc1.

Actin binding LIM 1 (abLIM1) negatively controls osteoclastogenesis by regulating cell migration and fusion.

Actin binding LIM 1 (abLIM1) is a cytoskeletal actin-binding protein that has been implicated in interactions between actin filaments and cytoplasmic targets. Previous biochemical and cytochemical studies have shown that abLIM1 interacts and co-localizes with F-actin in the retina and muscle. However, whether abLIM1 regulates osteoclast differentiation has not yet been elucidated. In this study, we examined the role of abLIM1 in osteoclast differentiation and function. We found that abLIM1 expression was upregulated during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation, and that a novel transcript of abLIM1 was exclusively expressed in osteoclasts. Overexpression of abLIM1 in the murine monocytic cell line, RAW-D suppressed osteoclast differentiation and decreased expression of several osteoclast-marker genes. By contrast, small interfering RNA-induced knockdown of abLIM1 enhanced the formation of multinucleated osteoclasts and markedly increased the expression of the osteoclast-marker genes. Mechanistically, abLIM1 regulated the localization of tubulin, migration, and fusion in osteoclasts. Thus, these results indicate that abLIM1 negatively controls osteoclast differentiation by regulating cell migration and fusion mediated via actin formation.

Genetic backgrounds and redox conditions influence morphological characteristics and cell differentiation of osteoclasts in mice.

Osteoclasts (OCLs) are multinucleated giant cells and are formed by the fusion of mononuclear progenitors of monocyte/macrophage lineage. It is known that macrophages derived from different genetic backgrounds exhibit quite distinct characteristics of immune responses. However, it is unknown whether OCLs from different genetic backgrounds show distinct characteristics. In this study, we showed that bone-marrow macrophages (BMMs) derived from C57BL/6, BALB/c and ddY mice exhibited considerably distinct morphological characteristics and cell differentiation into OCLs. The differentiation of BMMs into OCLs was comparatively quicker in the C57BL/6 and ddY mice, while that of BALB/c mice was rather slow. Morphologically, ddY OCLs showed a giant cell with a round shape, C57BL/6 OCLs were of a moderate size with many protrusions and BALB/c OCLs had the smallest size with fewer nuclei. The intracellular signaling of differentiation and expression levels of marker proteins of OCLs were different in the respective strains. Treatment of BMMs from the three different strains with the reducing agent N-acetylcysteine (NAC) or with the oxidation agent hydrogen peroxide (H(2)O(2)) induced changes in the shape and sizes of the cells and caused distinct patterns of cell differentiation and survival. Thus, genetic backgrounds and redox conditions regulate the morphological characteristics and cell differentiation of OCLs.