• 구강회복응용과학지
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• 제32권2호
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• pp.93-101
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• 2016

건강에 대한 관심과 평균 수명 증가로 보철수복을 위해 치과에 내원하는 고령 환자의 수도 증가하고 있다. 고령 환자는 다양한 만성 질환을 가지고 있는 경우가 많다. 특히 골다공증은 고령 환자에서 매년 증가하는 추세로 치과에 내원하는 골다공증 환자 수는 더욱 증가할 전망이다. 현재 비스포스포네이트 제재가 골다공증 치료에 가장 많이 사용되며 장기간 경구복용 하거나 주사제를 투여받은 환자에서 악골괴사가 부작용으로 보고되었다. 이러한 약제관련 악골괴사는 외과적인 치과치료가 원인이 되는 경우가 많고 발병하면 치유가 어려워 예방이 중요하다. 보철 수복을 위한 구강형성 과정에서 외과적 치료가 필요할 수 있으며, 골다공증 환자의 성공적인 치료를 위해 치과의사는 질환에 대해 충분히 이해하고 관심을 가져야 한다.

• 대한치과의사협회지
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• 제46권10호
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• pp.623-632
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• 2008

Purpose : The purpose of this study is to identify the effect of zoledronate(Zometa(R)), which is most common nitrogen containing bisphosphonate, on survival, proliferation, and differentiation of osteoblast. Material & Methods: Twenty four cell culture plates containing essential medium were seeded with UMR-106 cell lines, at density of 5 x $10^4 cells per plates. Each plates were incubated with 5% $CO^2 incubator at $37^{\circ}C$. Starting from 2 days after incubation, cell culture medias were replaced, and added with osteogenesis induction media and 0, 0.01, 0.1, 0.5, 1, $3\muM$ of zoledronate(Zometa(R)), every 2 days, for 12 days. Control group was plates not added with zoledronate($0\muM$), and experiment group were plates added with different concentration of zoledronates(0, 0.01, 0.1, 0.5, 1, $3\muM$). Mature osteoblasts were identified with Alizarine Red staining, and protein samples were collected. Optical density was determined at wavelength of 405nm with ELISA reader. For viability analysis, cells were harvested and incubated with propidium iodide, and analysed with flow cytometry. Western blot technique was used to analyse Runx2 protein of osteoblast. Results : Secretion of bone matrix decreased as zoledronate concentration increased, and zoledronate did not effect survival rate of UMR-106 cells when measured with flow cytometer. Expression of Runx2 protein was inhibited as zoledronate concentration increased. Conclusion : From the results, we were able to identify that increase of zoledronate concentration inhibited differentiation of UMR-106 cell to osteoblast, without effecting quantity or survival rate.

• Journal of International Society for Simulation Surgery
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• 제2권1호
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• pp.1-6
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• 2015

Purpose Bisphophonate-related osteonecrosis of the jaw (BRONJ) is an emerging problem. Extensive osteonecrosis of the jaw needs free flap reconstruction. Free fibular flap is the most useful flap for maxilla-mandibular hard and soft tissue reconstruction. The advantages of fibular free flap are simultaneous soft and hard tissue reconstruction and placing implant in reconstructed mandible and maxilla. In this study, four consecutive BRONJ patients who underwent fibula free flap reconstruction using simulation surgery were reviewed. Materials and Methods Four BRONJ patients who underwent free fibula reconstruction between May 2006 and September 2014 were included in this study. Male to female ratio was 1:3 and average age was 67.3 years old (62-70). All patients need mandibular bone reconstruction. Three patients suffered from osteoporosis and one male patient had multiple myeloma. Postoperative flap survival, functional reconstruction, esthetic results, food taking were evaluated. Results Three osseous flaps and one osteocutaneous flap were used. All the fibular flaps were survived and patients were recovered without complications. Oro-cutaneous fistula was resolved after operation. All patients were satisfied with the esthetic results. Patients reported improved solid food intake after operation with partial denture. One fully edentulous patient had semi-fluid diet after operation. Conclusion Treatment of the BRONJ is difficult due to lack of standard protocol. Fibular free flap using simulation surgery is the workhorse flap for mandibular hard and soft tissue reconstruction, especially in stage III BRONJ patient. In this study, functional and esthetic results were successful in all patients. Normal diet was possible with partial dentures.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제44권4호
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• pp.174-181
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• 2018

Objectives: The number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing, but treatment remains controversial. Published papers and systematic reviews have suggested that surgical treatment is effective in patients with MRONJ. The purpose of this study was to determine whether preoperative University of Connecticut Osteonecrosis Numerical Scale (UCONNS), other serologic biomarkers, and size of necrosis are prognostic factors for outcome of surgical treatment in MRONJ. Materials and Methods: From January 2008 to December 2016, 65 patients diagnosed with MRONJ at the Department of Oral and Maxillofacial Surgery in College of Dentistry, Dankook University who required hospitalization and surgical treatment were investigated. Patient information, systemic factors, and UCONNS were investigated. In addition, several serologic values were examined through blood tests one week before surgery. The size of osteolysis was measured by panoramic view and cone-beam computed tomography in all patients. With this information, multivariate logistic regression analysis with backward elimination was used to examine factors affecting postoperative outcome. Results: In multivariate logistic analysis, higher UCONNS, higher C-reactive protein (CRP), larger size of osteolysis, and lower serum alkaline phosphate were associated with higher incidence of incomplete recovery after operation. This shows that UCONNS, CRP, serum alkaline phosphate, and size of osteolysis were statistically significant as factors for predicting postoperative prognosis. Conclusion: This study demonstrated that CRP, UCONNS, serum alkaline phosphate, and size of osteolysis were statistically significant factors in predicting the prognosis of surgical outcome of MRONJ. Among these factors, UCONNS can predict the prognosis of MRONJ surgery as a scale that includes various influencing factors, and UCONNS should be used first as a predictor. More aggressive surgical treatment and more definite surgical margins are needed when the prognosis is poor.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제39권
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• pp.1.1-1.7
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• 2017

Background: Multiple myeloma (MM) is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Bisphosphonates (BP) are used as supportive therapy in the management of MM. This study aimed to analyze the incidence, risk factors, and clinical outcomes of medication-related necrosis of the jaw (MRONJ) in MM patients. Methods: One hundred thirty MM patients who had previous dental evaluations were retrospectively reviewed. Based on several findings, we applied the staging and treatment strategies on MRONJ. We analyzed gender, age, type of BP, incidence, and local etiological factors and assessed the relationship between these factors and the clinical findings at the first oral examination. Results: MRONJ was found in nine male patients (6.9%). The mean patient age was 62.2 years. The median BP administration time was 19 months. Seven patients were treated with a combination of IV zoledronate and pamidronate, and two patients received single-agent therapy. The lesions were predominantly located in the mandible (n = 8), and the most common predisposing dental factor was a history of prior extraction (n = 6). Half of the MRONJ were related to diseases found on the initial dental screen. Patients with MRONJ were treated with infection control and antibiotic therapy. When comparing between the MRONJ stage and each factor (sign, location, etiologic factor, BP type, treatment, and outcome), there were no significant differences between stages, except for between the stage and sign (with or without purulence). Conclusions: For prevention of MRONJ, we recommend routine dental examinations and treatment prior to starting BP therapy.

• 대한치과의사협회지
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• 제52권4호
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• pp.218-233
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• 2014

Bispbosphonates are a class of pharmaceutic agents, which induce apoptosis of osteoclast as well as impair osteoclastic activity to suppress bone resorption. Thus, bisphophonates are effectively used to treat osteoporosis, multiple myeloma and to prevent bone metastases of malignant cancer. However, recently dental disease have been reported associated with Bisphosphonates. Thus, there are a number of discussions about proper prevention and treatment of bisphosphonate-related osteonecrosis of jaw(BRONJ). Marshall R. Urist in 1965 made the seminal discovery that a specific protein, BMP(bone morphogenetic protein), found in the extracellular matrix of demineralized bone could induce bone formation newly when implanted in extraosseous tissues in a host. BMPs are multi-functional growth factors which are members of the transforming growth factor-beta super family and their ability is that plays a pivotal roll in inducing bone. About 18 BMP family members have been identified and characterized. Among of them, BMP-2 and BMP-7 have significant importance in bone development. In this study, patients of BRONJ were recieved who visited Department of oral and maxillofacial surgery, school of dentistry, Wonkwang university for past 3 years from 2011 to 2013. We focused on the results of the surgical intervention. We suggest that new strategy of treatment used to rhBMP-2 and LFA(Lidocaine-Fibrinogen-Aprotinin)-collagen scaffold for patients of BRONJ. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on rhBMP-2 and LFA collage scaffold.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.563-569
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• 2014

Materials with differing surfaces have been developed for clinical implant therapy in dentistry and orthopedics. This study was designed to evaluate bone response to titanium alloy containing Ti-32Nb-5Zr with nanostructure, anodic oxidation, heat treatment, and ibandronate coating. Rats were randomly assigned to two groups for implantation of titanium alloy (untreated) as the control group and titanium alloy group coated with ibandronate as the experimental group. Then, the implants were inserted in both tibiae of the rats for four weeks. After implantation, bone implant interface, trabecular microstructure, mechanical fixation was evaluated by histology, micro-computed tomography (${\mu}CT$) and the push-out test, respectively. We found that the anodized, heat-treated and ibandronate-coated titanium alloy triggered pronounced bone implant integration and early bone formation. Ibandronate-coated implants showed elevated values for removal torque and a higher level of BV/TV, trabecular thickness and separation upon analysis with ${\mu}CT$ and mechanical testing. Similarly, higher bone contact and a larger percentage bone area were observed via histology compared to untreated alloy. Furthermore, well coating of ibandronate with alloy was observed by vitro releasing experiment. Our study provided evidences that the coating of bisphosphonate onto the anodized and heat-treated nanostructure of titanium alloy had a positive effect on implant fixation.

• Restorative Dentistry and Endodontics
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• 제44권2호
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• pp.17.1-17.10
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• 2019

Objectives: Root resorption is an unexpected complication after replantation procedures. Combining anti-osteoclastic medicaments with retrograde root filling materials may avert this resorptive activity. The purpose of this study was to assess effects of a cathepsin K inhibitor with calcium silicate-based cements on osteoclastic activity. Methods: MC3T3-E1 cells were cultured for biocompatibility analyses. RAW 264.7 cells were cultured in the presence of the receptor activator of nuclear factor-kappa B and lipopolysaccharide, followed by treatment with Biodentine (BIOD) or ProRoot MTA with or without medicaments (Odanacatib [ODN], a cathepsin inhibitor and alendronate, a bisphosphonate). After drug treatment, the cell counting kit-8 assay and Alizarin red staining were performed to evaluate biocompatibility in MC3T3-E1 cells. Reverse-transcription polymerase chain reaction, tartrate-resistant acid phosphatase (TRAP) staining and enzyme-linked immunosorbent assays were performed in RAW 264.7 cells to determine the expression levels of inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and prostaglandin E2 (PGE2). Data were analyzed by one-way analysis of variance and Tukey's post hoc test (p < 0.05). Results: Biocompatibility results showed that there were no significant differences among any of the groups. RAW 264.7 cells treated with BIOD and ODN showed the lowest levels of $TNF-{\alpha}$ and PGE2. Treatments with BIOD + ODN were more potent suppressors of inflammatory cytokine expression (p < 0.05). Conclusion: The cathepsin K inhibitor with calcium silicate-based cement inhibits osteoclastic activity. This may have clinical application in preventing inflammatory root resorption in replanted teeth.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제45권5호
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• pp.260-266
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• 2019

Objectives: Dental implants shorter than 8 mm, called short dental implants (SDIs), have been considered to have a lower success rate than standard length implants. But recent studies have shown that SDIs have a comparable success rate, and implant diameter was more important for implant survival than implant length. Also, SDIs have many advantages, such as no need for sinus lifting or vertical bone grafting, which may limit use in medically compromised patients. Materials and Methods: In this study, 33 patients with 47 implants 7-mm long were examined over the last four years. All patients had special medical history and were categorized into 3 groups: systemic disorders, such as diabetes mellitus (controlled or uncontrolled), mental disability, and uncontrolled hypertension; oral cancer ablation with reconstruction, with or without radiotherapy; diverse osteomyelitis, such as osteoradionecrosis and bisphosphonate-related osteonecrosis of the jaw. Most of these patients have insufficient residual bone quality due to mandible atrophy or sinus pneumatization. Results: The implant diameters were 4.0 (n=38), 4.5 (n=8), and 5.0 mm (n=1). Among the 47 implants placed, 2 implants failed before the last followup. The survival rate of 7-mm SDIs was 95.74% from stage I surgery to the last follow-up. Survival rates did not differ according to implant diameter. The mean marginal bone loss (MBL) at 3 months, 1 and 2 years was significantly higher than at implant installation, and the MBL at 1 year was also significantly higher than at 3 months. MBL at 1 and 2 years did not differ significantly. Conclusion: Within the limitations of the present study, the results indicate that SDIs provide a reliable treatment, especially for medically compromised patients, to avoid sinus lifting or vertical bone grafting. Further, long-term follow-up is needed.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제47권2호
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• pp.99-111
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• 2021

Objectives: It is unclear whether the extent of intraoral mucosa defects in patients with medication-related osteonecrosis of the jaw indicates disease severity. Therefore, this study investigated whether mucosal lesions correlate with the true extent of osseous defects in stage I patients. Materials and Methods: Retrospectively, all patients with stage I medication-related osteonecrosis of the jaw who underwent surgical treatment between April 2018 and April 2019 were enrolled. Preoperatively, the extent of their mucosal lesions was measured in clinical evaluations, and patients were assigned to either the visible or the probeable bone group. Intraoperatively, the extent of necrosis was measured manually and with fluorescence. Results: Fifty-five patients (36 female, 19 male) with 86 lesions (46 visible bone, 40 probeable bone) were enrolled. Intraoperatively, the necrotic lesions were significantly larger (P<0.001) than the preoperative mucosal lesions in both groups. A significant (P<0.05) but very weak (R2<0.2) relationship was noted between the extent of the mucosal lesions and the necrotic bone area. Conclusion: Preoperative mucosal defects (visible or probeable) in patients with medication-related osteonecrosis of the jaw do not indicate the extent of bone necrosis or disease severity.