• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제42권5호
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• pp.271-277
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• 2016

Objectives: The objective of this study was to retrospectively investigate the association of diseases having an influence on inhibition of angiogenesis such as hypertension, diabetes mellitus type II, hypercholesterolemia, and rheumatoid arthritis (RA) with the development of osteonecrosis of the jaws. Materials and Methods: The 135 patients were allocated into 4 groups of bisphosphonate-related osteonecrosis of the jaw (BRONJ) group (1A); non-BRONJ group (1B); osteonecrosis of the jaw (ONJ) group (2A); and control group (2B), according to histologic results and use of bisphosphonate. This retrospective study was conducted with patients who were treated in one institute from 2012 to 2013. Fisher's exact test and logistic regression analysis were used to analyze the odds ratios of diseases having an influence on inhibition of angiogenesis for development of ONJ. Results: The effects of diabetes and hypertension were not statistically significant on development of ONJ. When not considering bisphosphonate use, RA exhibited a high odds ratio of 3.23 (P=0.094), while hyperlipidemia showed an odds ratio of 2.10 (P=0.144) for development of ONJ. More than one disease that had an influence on inhibition of angiogenesis showed a statistically significant odds ratio of 2.54 (P=0.012) for development of ONJ. Conclusion: Patients without diseases having an influence on inhibition of angiogenesis were at less risk for developing ONJ.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제35권5호
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• pp.302-309
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• 2013

Purpose: This study evaluated the prognosis of conservative and surgical treatment according to the staging of bisphosphonate-related osteonecrosis of jaw (BRONJ) by American Association of Oral and Maxillofacial Surgeons and American Society for Bone and Mineral Research. Methods: We evaluated 53 patients of BRONJ who visited Department of Dentistry, Ajou University School of Medicine from May 2007 to February 2013. Twenty eight patients in stage 2, were divided into surgical and conservative groups with cessation of bisphosphonate therapy. Fifteen patients belonged to the conservative treatment group, in which mouth rinsing and antibiotics medication were done. Thirteen patients were treated with debridement or sequestrectomy, in the surgical treatment group. Each study list was analyzed by SPSS ver. 14.0 (SPSS Inc., USA) software and the favorable rate was verified by the Fisher exact test. P-values less than 0.05% were deemed significant. Results: Clinical outcome was evaluated on the basis of both clinical and radiographic findings. Of all the 28 patients of stage 2, 15 patients underwent conservative treatment and 13 patients received surgical treatment. In the surgical group, 9 of 13 (69.2%) showed good prognosis, 4 of 13 (30.7%) showed recurrence. In the conservative group, 13 of 15 (86.6%) showed no change duting the follow-up period. Two of 15 patients even showed a bad prognosis, such as pain and pus discharge, which are criteria for stage 3. P-value was 0.067 (>0.05). Conclusion: The results of the present study suggests that surgical intervention is good choice against the conservative treatment, after proper drug holidays period, while further investigation is needed for a definite solution to BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권1호
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• pp.54-61
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• 2011

Introduction: Bisphosphonates is used widely for the treatment of the Paget's disease, multiple myeloma, bone metastases of malignant tumors with the prevention of pain and their pathological fracture. However, it was recently suggested that bisphosphonates related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate use. Materials and Methods: Twenty-four individuals, who were referred to the Department of Oral and Maxillofacial surgery, Dankook University Dental Hospital, were selected from those who had exposed bone associated with bisphosphonates from January, 2005 to December, 2009 according to the criteria of American Association of Oral and Maxillofacial Surgeons (AAOMS) for BRONJ. The patients group consisted of 7 males and 17 females between the age of 46 to 78 years (average 61.8 years). Each patient had panoramic imaging, computed tomography (CT), whole body bone scanning performed for a diagnosis and biopsy sampling from the necrotizing tissue. C-terminal cross-linking telopeptide of type I collagen (CTX) level of patients who had undergone surgical intervention was measured 7 days before surgery. Results: The main cause of bone exposure was post-extraction (15), chronic periodontitis (4), persistent irritation of the denture (3). Twenty people had undergone BRONJ treatment for two to eight months except for 4 people who had to maintain the bisphosphonates treatment to prevent a metastasis and bone trabecular pain with medical treatment. When the bisphosphonate treatment was suspended at least for 3 months and followed up according to the AAOMS protocols, the exposed necrotizing bones were found to be covered by soft tissue. Conclusion: Prevention therapy, interruption of bisphophonates for at least 3 months and cooperation with the physician for conservative treatment are the essential for treating BRONJ patient with high risk factors. The CTX level of BRONJ patients should be checked before undergoing surgical intervention. Surgical treatments should be delayed in the case of a CTX level <150 pg/mL.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제39권1호
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• pp.9-13
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• 2013

Objectives: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. Materials and Methods: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. Results: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was $70.0{\pm}10.1$ years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. Conclusion: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.

• 대한치과보철학회지
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• 제53권1호
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• pp.39-45
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• 2015

하악골 연속성의 상실은 하악 기능의 균형과 대칭에 영향을 주며, 하악의 움직임에 변화를 유발하고 절제된 부위로 잔존하악골을 편위시킨다. 또한 연하, 발음, 하악의 운동, 저작, 호흡과 같은 다른 부분에서도 기능이상을 나타낸다. 하악골의 일부가 결손된 환자의 경우, 일반적으로 외과적 재건에 이어 보철적 수복이 이루어진다. 하지만 BRONJ (Bisphosphonate related osteonecrosis of the Jaw)와 같은 전신적 질환을 가진 환자의 경우, 외과적 재건의 적용에 제한이 있게 되고 전적으로 보철적 수복에 의지하게 된다. 다양한 보철적 방법이 하악의 변위를 최소화하고 저작 효율과 기능 및 심미를 개선하기 위하여 제시되었다. 가철성 국소의치로 치료 시, 입술, 뺨, 혀의 운동에 의해 측방 및 수평력이 발생하며 기능 인상을 통해 이를 최대한 줄여 주어야 한다. 또한, Twin occlusion을 사용하면 적절한 구순 및 협측의 지지를 얻으면서 교합관계의 형성을 가능하게 할 수 있다. 이 증례보고에서는 하악골 결손 증례에서 중립대 인상 방법과 twin occlusion을 통하여 기능적 심미적으로 만족할 만한 결과를 얻었기에 이를 보고하고자 한다.

• Parasites, Hosts and Diseases
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• 제55권4호
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• pp.433-437
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• 2017

Pentastomiasis, a zoonotic parasite infection, is typically found in the respiratory tract and viscera of the host, including humans. Here, we report for the first time an extremely rare case of intraosseous pentastomiasis in the human maxilla suffering from medication related osteonecrosis of the jaw (MRONJ). A 55-year-old male had continuously visited the hospital for MRONJ which had primarily developed after bisphosphonate and anti-neoplastic administration for previous bone metastasis of medullary thyroid cancer. Pain, bone exposure, and pus discharge in the right mandible and left maxilla were seen. Osteolysis with maxillary cortical bone perforation at the left buccal vestibule, palate, nasal cavity, and maxillary sinus was observed by radiologic images. A biopsy was done at the left maxilla and through pathological evaluation, a parasite with features of pentastome was revealed within the necrotic bone tissue. Further history taking and laboratory evaluation was done. The parasite was suspected to be infected through maxillary open wounds caused by MRONJ. Awareness of intraosseous pentastomiasis should be emphasized not to be missed behind the MRONJ. Proper evaluation and interpretation for past medical history may lead to correct differential diagnosis and therapeutic intervention for parasite infections.

• 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.

• 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.