• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권3호
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• pp.158-163
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• 2009

Objective : Recently, we are interested in bisphosphonate related osteonecrosis of the jaw (BRONJ). Most of patients with osteonecrosis have taken medicine bisphosphonate for a long time. But the mechanism of osteonecrosis in BRONJ was not clarified yet. The aim of this study is to evaluate the difference of bone healing effect after bone graft from ilium to maxillary sinus in rabbits between zoledronate-treated and zoledronate-not treated groups. Method : The subjects was divided into two groups. The experimental group was 9 rabbits, treated with intraperitoneal administration of zoledronate(0.06mg/kg) once per week for 3 weeks. In control group, same procedure was applied but administerd saline instead of zoledronate. After 4 weeks, surgical operation under local anesthesia (ketamine 3.0cc, xylazine 1.0cc) was done. At postoperative 1, 2, 4, 8 weeks later, each rabbits were sacrificed and removed the bone grafted area. Gross, radiologic and histopathologic exminations of bone grafted area were performed. Result : There were no conspicuous differences of radiological findings between experimental and control groups in any experimental weeks. In experimental group, new bone formation appeared earlier than control group at 1 week after operation, and maturation of bony tissue were more conspicuous at 2 and 4 weeks after operation, compared with control group. In 8 weeks after operation, similar microscopic findings were noted in both groups. Conclusion : In the bisphosphonate-treated rabbits, new bone formation in the bone grafted area appeared earlier and bony maturation was more concpicuous, even though there were no significant differences of gross and radiological findings. These findings suggest that bisphosphonate might be promotive effect in the healing process in early stage after administration.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권3호
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• pp.153-157
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• 2009

Recently, an increasing number of bisphosphonate related osteonecrosis of the jaw(BRONJ) is being reported. A guideline has been already established in the US, but it does not seem to be fully recognized by clinicians in Korea. Therefore, a survey study was done to inform and have clinicians realize the seriousness of BRONJ. 1,341 practitioners were randomly selected out of 13,405 practitioners(by Feb of 2008, KDA) in Korea. A questionnaire was given to them between May to July in 2008. Questions were designed to investigate each respondent's experience term years in the clinic, occupation, speciality, awareness on risk of bisphosphonate, experience on treating osteonecrosis patients, awareness about the guideline on BRONJ suggested by AAOMS and whether if they ask about bisphosphonate medication history to patients before invasive treatment. 45.1% of the clinicians have reported on experiencing delayed healing on bone exposed site after extraction both in the maxilla and the mandible. However, clinicians have asked the patients whether if they are on bisphosphonate or not in only 15.1% of these cases. 56.5% of the clinicians simply knew about BRONJ but only 28.9% of the clinicians were aware that bisphosphonate can cause osteonecrosis after invasive dental treatment. Only 19.3% knew about the contents of guideline on BRONJ and 57.2% were aware of the seriousness of BRONJ. Clinicians with shorter clinical experience term were more aware of BRONJ and the guideline on BRONJ than the experienced clinicians. But awareness of the possibility of BRONJ after invasive dental treatment were about the same regardless of their clinical experience. The results show that Korean clinicians need to be more aware about BRONJ. Data on BRONJ cases in Korea should be collected and provided with additional education to let Korean clinicians know and be more aware about BRONJ.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제38권
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• pp.46.1-46.7
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• 2016

Background: Osteoradionecrosis is the most dreadful complication after head and neck irradiation. Orocutaneous fistula makes patients difficult to eat food. Fibular free flap is the choice of the flap for mandibular reconstruction. Osteocutaneous flap can reconstruct both hard and soft tissues simultaneously. This study was to investigate the success rate and results of the free fibular flap for osteoradionecrosis of the mandible and which side of the flap should be harvested for better reconstruction. Methods: A total of eight consecutive patients who underwent fibula reconstruction due to jaw necrosis from March 2008 to December 2015 were included in this study. Patients were classified according to stages, primary sites, radiation dose, survival, and quality of life. Results: Five male and three female patients underwent operation. The mean age of the patients was 60.1 years old. Two male patients died of recurred disease of oral squamous cell carcinoma. The mean dose of radiation was 70.5 Gy. All fibular free flaps were survived. Five patients could eat normal diet after operation; however, three patients could eat only soft diet due to loss of teeth. Five patients reported no change of speech after operation, two reported worse speech ability, and one patient reported improved speech after operation. The ipsilateral side of the fibular flap was used when intraoral soft tissue defect with proximal side of the vascular pedicle is required. The contralateral side of the fibular flap was used when extraoral skin defect with proximal side of the vascular pedicle is required. Conclusions: Osteonecrosis of the jaw is hard to treat because of poor healing process and lack of vascularity. Free fibular flap is the choice of the surgery for jaw bone reconstruction and soft tissue fistula repair. The design and selection of the right or left fibular is dependent on the available vascular pedicle and soft tissue defect sites.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권1호
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• pp.1-8
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• 2011

Introduction: The utility of the C-terminal cross-linking telopeptide test (CTX) as a method for staging Bisphosphonate-related osteonecrosis of the jaws (BRONJ) and its healing process was examined. Materials and Methods: A total 19 patients who were diagnosed with BRONJ underwent a fasted morning CTX test, were enrolled in this study. The serum CTX values ranged from 50 to 630 pg/mL (mean 60). The risk assessment was rated according to the CTX values of the individual patient (minimal risk, ${\geq}$ 150 pg/mL, moderate, 100 to 150 pg/mL, high, ${\leq}$100 pg/mL). The BRONJ scores were then calculated according to the number of BRONJ lesions and their stage. The operation was done as soon as possible, regardless of BORNJ stage. Results: The mean duration of bisphosphonate therapy was 4.1 years. Of the 19 patients, 15, 2 ans 2 received alendronate, risedronate and zoledronate, respecively. Of the 19 patients who underwent a sequestrectomy, saucerization and smoothing, 15 healed after the initial surgery, 1 patient healed after one more surgical procedure, 3 patients did not heal completely but showed improvement in symptoms. Therefore, 17 out of the 19 patients healed completely with complete mucosal coverage and the elimination of pain. The risk assessment using the CTX value and disease severity were not correlated (r=-0.264, P=0.275). In addition, the risk assessment using CTX value and healing after surgery were not correlated (r=-0.147, P=0.547). Conclusion: The serum CTX should be considered carefully by clinicians as part of overall management. Early surgical intervention is of benefit in the treatment of stage II BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제43권3호
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• pp.212-212
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• 2017

• 대한치위생과학회지
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• 제3권2호
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• pp.59-66
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• 2020

Dental hygienists handle periodontal tissue every day. Since periodontal tissue contains hard and soft tissue, dental hygienists need to cultivate scientific knowledge about bone tissue. This study introduces recent research results on cells and cytokines related to bone tissue. Recently, bisphosphonate-related osteonecrosis of the jaw has been reported, therefore we would like to present osteoporosis and osteoporosis treatment drugs and their side effects in this study.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제32권1호
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• pp.16-22
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• 2010

Objective: Bisphosphonate related osteonecrosis of the jaw (BRONJ) is reported in patients taken bisphosphonate for a long time, however, the mechanism of osteonecrosis in BRONJ was not clarified yet. This study was designed to investigate the effect of short administraion zoledronate on the healing pattern of periosteum and sinus membrane after iliac bone graft into maxillary sinus. Methods: In this study, 18 Newzeland rabbits were used. The animals were divided into 2 group. In the experimental group, rabbits were treated with weekly peritoneal injection (0.06 mg/kg/week) of zoledronate for three times. In the control group, rabbits were treated with saline solution injection instead of zoledronate. Periosteum and sinus membrane were harvested from one rabbit of the experimental group and one of the control group in the fourth week. The autogeneous bone was harvested from ilium and grafted into maxillary sinus. The rabbits were sacrificed at 1, 2, 4 and 8 weeks after bone graft. The healing pattern of periosteum and sinus membrane were evaluated histologically. Results: Inflammatory reaction in the periosteum was less conspicuous and healing process appeared earlier in experimental group compared with control group at 1, 2, 4 weeks. There were no differences of microscopic findings of sinus membrane between both groups at any weeks. Conclusion: Short-term use of zoledronate decreased the inflammatory reaction and enhanced healing process in the periosteum. These findings suggest the possibility that zoledronte suppress the function of macrophages.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제38권3호
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• pp.152-159
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• 2012

Objectives: This study evaluated bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients diagnosed with malignant bone tumors. Demographic findings, laboratory, and radiographic analyses were performed to characterize disease severity and progression. Materials and Methods: Patients who had been diagnosed with BRONJ (2005-2010) at the authors' hospital according to the American Association of Oral and Maxillofacial Surgeons were investigated. Twenty-one patients (12 with multiple myelomas, 7 with breast cancer, and 2 with prostate cancer) who had been treated with bisphosphonates (BPs) for malignant bone tumors were included. Radiographic evaluations with a panorama, computed tomography, whole body bone scan, and laboratory findings were evaluated for erythrocyte sedimentation rate (ESR), c-reactive proteins (CRPs), and c-terminal cross-linked telopeptides (CTXs). Results: The average age of the patients was 64.3 (range 51-80), and they were treated with BPs for an average of $35{\pm}19$ months before BRONJ was diagnosed. Types of BPs were zolendronic acid (81%, intravenous [IV]), pamidronate (4.8%, IV), zoledronic acid+pamidronate (4.8%, IV), alendronate (4.8%, per os [PO]), and ibadronate (4.75%, PO). Extraction (67%) and persistent irritation of dentures (20%) were the most common triggering factors. BRONJ in the mandible was reported in 62% of the cases, in the maxilla 24%, and both 14%. BRONJ occurred more frequently in patients with multiple myelomas (n=12, 57.1%). Most of the patients revealed an advanced BRONJ stage; Stage I (n=2, 9%), Stage II (n=13, 62%), and Stage III (n=6, 29%). Conclusion: The differences of the ESR, CRP, and CTX values between the BRONJ-recurring and non-recurring patients after the treatment were not evident. Later stage BRONJ patients showed lower CTX levels. A drug holiday after the diagnosis of BRONJ did not remarkably influence the surgical outcomes. However, the limited number of patients in the study should be considered.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권6호
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• pp.397-402
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• 2009

The purpose of this study is to investigate the effects of alendronate and pamidronate on proliferation and the alkaline phosphatase activity of human bone marrow derived mesenchymal stem cells and to relate the results with bisphosphonate related osteonecrosis of the jaw(BRONJ). With the consent of patients with no systemic disease and undergoing iliac bone graft, cancellous bone was collected to obtain human bone marrow derived mesenchymal stem cells through cell culture. 96 well plate were prepared with a concentration of $10^4$cell/ well. Alendronate and pamidronate were added to each well with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively. Then proliferation capacity of each well was evaluated with the cell counting kit. 24 well plates were prepared with a concentration of $10^5$cell/ml/well and with the bone supplement, alendronate and pamidronate were added with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively on each plate. The plates were cultured for either 24 or 72 hours. Then the cells were sonicated to measure the alkaline phosphatase activity and protein assay was done to standardize the data for analysis. As the concentration of alendronate or pamidronate added to the culture increased, the proliferation capacity of the cells decreased. However, no statistical significance was found between the group with $10^{-10}M$ of bisphophonate and the control group. Pamidronate was not capable of increasing the alkaline phosphatase activity in all trials. However, alkaline phosphatase activity increased with 24 hours of $10^{-8}M$ of alendronate treatment and with 48 hours of $10^{-10}M$ of alendronate treatment. Cell toxicity increased as the bisphosphonate concentration increased. This seems to be associated with the long half life of bisphosphonate, resulting in high concentration of bisphosphonate in the jaw and thus displaying delayed healing after surgical procedures. Alendronate has shown to increase the alkaline phophatase activity of human bone marrow derived mesenchymal stem cells. However, this data is insufficient to conclude that alendronate facilitates the differentiation of human bone marrow derived mesenchymal stem cells. Further studies on DNA level and animal studies are required to support these results.