• 대한소아치과학회지
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• 제27권2호
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• pp.309-317
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• 2000

본 실험은 bisphosphonate가 조골세포 분화 및 파골세포 분화에 미치는 영향을 알아보고자, etidronate와 alendronate를 조골세포에 투여하여 조골세포 전사인자인 Cbfa1, 조골세포 표시 인자의 발현, 석회화된 골결절 형성을 평가하였다. Bisphosphonate가 조골세포의 석회화된 골결절 형성에 미치는 영향을 평가하기 위하여 배양액에 $10^{-6},\;10^{-5},\;10^{-4}M$의 etidronate 및 $10^{-8},\;10^{-7},\;10^{-6}M$의 alendronate를 첨가하였으며, 배양 15일 후에 alizarin red로 염색하여 관찰하였다. 또 조골세포의 분화에 미치는 bisphosphonate의 영향을 평가하고자 백서 두개관에서 얻은 조골세포에 etidronate $10^{-6},\;10^{-5},\;10^{-4}M$ 및 alendronate $10^{-6}$ M을 투여하고 배양 8일 후 총RNA를 수집하였고, 전기영동 및 Northern blot hybridization하여 Cbfa1, alkaline phosphatase, type I collagen, osteopontin, osteocalcin의 발현을 조사하였다. 이상의 실험결과 다음과 같은 결론을 얻었다. 1. Etidronate는 농도 의존적으로 골결절 석회화를 억제하였으나, alendronate는 골석회화를 억제하지 않았다. 2. Etidronate는 Cbfa1의 발현을 농도 의존적으로 억제하였으나, alendronate는 오히려 촉진하였다. 3. Etidronate는 type I collagen, osteocalcin 및 osteopontin의 발현을 농도 의존적으로 억제하였으나, alendronate는 오히려 증가시켰다. 4. Alkaline phosphatase의 발현은 사용된 etidronate와 alendronate에 의해 영향 받지 않았다. 이상의 결과에서 etidironate는 조골세포의 전사인자인 Cbfa1의 발현을 억제하며, 이에 의하여 조골세포의 분화표지인자인 type I collagen, osteopontin 및 osteocalcin의 합성이 억제되고, 결과적으로 석회화된 골결절의 형성을 억제하는 것으로 사료된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제43권1호
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• pp.16-22
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• 2017

Objectives: Bisphosphonate is the primary cause of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are eliminated from the human body by the kidneys. It is anticipated that bisphosphonate levels in the body will increase if the kidney is in a weak state or if there is systemic disease that affects kidney function. The aim of this study was to analyze the relevance of renal function in the severity of BRONJ. Materials and Methods: Ninety-three patients diagnosed with BRONJ in Pusan National University Dental Hospital from January 2012 to December 2014 were included in this study. All patients underwent a clinical exam, radiographs, and serologic lab test, including urine analysis. The patient's medical history was also taken, including the type of bisphosphonate drug, the duration of administration and drug holiday, route of administration, and other systemic diseases. In accordance with the guidelines of the 2009 position paper of American Association of Oral and Maxillofacial Surgeons, the BRONJ stage was divided into 4 groups, from stage 0 to 3, according to the severity of disease. IBM SPSS Statistics version 21.0 (IBM Co., USA) was used to perform regression analysis with a 0.05% significance level. Results: BRONJ stage and renal factor (estimated glomerular filtration rate) showed a moderate statistically significant correlation. In the group with higher BRONJ stage, the creatinine level was higher, but the increase was not statistically significant. Other factors showed no significant correlation with BRONJ stage. There was a high statistically significant correlation between BRONJ stage and 'responder group' and 'non-responder group,' but there was no significant difference with the 'worsened group.' In addition, the age of the patients was a relative factor with BRONJ stage. Conclusion: With older age and lower renal function, BRONJ is more severe, and there may be a decrease in patient response to treatment.

• 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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• 제42권4호
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• pp.193-204
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• 2016

Objectives: This study examined the statistical relevance of whether the systemic predisposing factors affect the prognosis of surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). All cases had undergone bone biopsies to determine the characteristics of the mechanisms of BRONJ by optical microscopy. Materials and Methods: The data included 54 BRONJ cases who underwent surgery and in whom bone biopsies were performed. The results of surgery were evaluated and the results were classified into 3 categories: normal recovery, delayed recovery, and recurrence after surgery. The medical history, such as diabetes mellitus, medication of steroids, malignancies on other sites was investigated for an evaluation of the systemic predisposing factors in relation to the prognosis. The three factors involved with the medication of bisphosphonate (BP) were the medication route, medication period, and drug holiday of BP before surgery. The serum C-terminal cross-linking telopeptide (CTX) value and presence of microorganism colony in bone biopsy specimens were also checked. Statistical analysis was then carried out to determine the relationship between these factors and the results of surgery. Results: The group of patients suffering from diabetes and on steroids tended to show poorer results after surgery. Parenteral medication of BP made the patients have a poorer prognosis after surgery than oral medication. In contrast, the medication period and drug holiday of BP before surgery did not have significance with the results of surgery nor did the serum CTX value and presence of microorganism colony. Necrotic bone specimens in this study typically showed disappearing new bone formation around the osteocytic lacunae and destroyed Howship's lacunae. Conclusion: Although many variables exist, this study could in part, predict the prognosis of surgical treatment of BRONJ by taking the patient's medical history.

• Journal of Korean Dental Science
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• 제7권1호
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• pp.38-42
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• 2014

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined as exposed necrotic bone without evidence of healing for at least 8 weeks in the maxillofacial area in a patient with history of bisphosphonate use. Obtaining complete coverage of the hard tissue by soft tissue in BRONJ patients is especially important. Therefore, managing the mucosa is one of the key factors in a successful outcome, but this is especially hard to achieve in BRONJ patients. Various applications of buccal fat pad in oral reconstruction-including the closure of surgical defects following tumor excision, repair of surgical defects following the excision of leukoplakia and submucous fibrosis, closure of primary and secondary palatal clefts, coverage of maxillary and mandibular bone grafts, and lining of sinus surface of maxillary sinus bone graft in sinus lift procedures for maxillary augmentation-have been studied. Eliminating all potential sites of infection and post-operative infection control is crucial in BRONJ. We present a case using the buccal fat pad pedicle for a stage 3 BRONJ defect. Uneventful total epithelialization of the buccal fat pad regardless of size was noted. In summary, the buccal fat pad has versatile application and various recipient sites for surgical utilization. It is an easy technique, with promising overall success rates. With careful selection and handling, buccal fat graft can resolve problems with soft tissue coverage in stage 2 or 3 BRONJ patients.

• 구강회복응용과학지
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• 제27권4호
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• pp.449-454
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• 2011

근래에 비스포스포테이트(bisphosphonate) 투약의 부작용으로 악골괴사에 관한 보고들이 점차적으로 증가하고 있다. 최근에 보고된 유병율은 대략 0.8% - 12 % 정도이다. 하악은 상악보다 2배 정도 호발하는 것으로 보고되었고 이의 60 - 70 %는 치과진료와 연관성이 거론되었다. 임상적으로 골괴사 현상이 일어나기 전에 건강한 치주조직에 변화가 일어나는데 치유지연 점막궤양, 치아동요와 원인을 알 수 없는 연조직 감염등이 관찰되었다. 치아발거가 치과영역에서 가장 흔한 사전 처치행위로 알려져 있다. 장기적인 비스포스포네이트 투약시 세심한 예방적 치과진료가 이러한 심각한 괴사로 이어지지 않도록 하는데 절대적이다.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제41권6호
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• pp.327-331
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• 2015

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurs mainly in female patients. In males the occurrence rate is low, which seems to be related to the low incidence of osteoporosis in men. Unfortunately, BRONJ tends to be ignored in general dental clinics in male patients with a history of osteoporosis treatment. BRONJ occurred in a male patient due to the clinician's lack of interest in the patient's history. In this case, the male patient was on bisphosphonate therapy because of a orchiectomy, and a dental treatment was performed without consideration of his medical history, resulting in BRONJ. We performed careful examinations and treatment with antibiotics and surgical operations. The postoperative healing was successful. In light of this particular case, we concluded that careful listening to the patient's history is very important.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권4호
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• pp.291-302
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• 2010

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of Bisphosphonates (BPs) use. These days, oral bisphosphonates are normally prescribed to treat osteoporosis. Intravenous BPs are used extensively to treat osteolytic bone lesions related to multiplemyeloma and bone metastasis of solid cancers, breast cancer or prostate cancer. As the prescription of BPs is universalized and the number of people treated with BPs is increasing, an accurate understanding and proper management of BRONJ are required. The aim of this study was to improve the clinicians' understanding of BRONJ by reviewing the literature. To achieve this, this paper introduces case reports as well as the current concept of BRONJ based on the 2009 updates by American Association of Oral and Maxillofacial (AAOMS) including the definition, epidemiology, etiology, diagnosis, treatment and prevention of BRONJ.

• Bulletin of the Korean Chemical Society
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• 제31권9호
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• pp.2561-2564
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• 2010

The accurate determination of bisphosphonate levels in bone and biological fluids is important in both clinical and pharmacological/toxicological studies; however, the quantitative analysis of the bisphosphonate is difficult because its concentration is quite low in most of biological sample. A novel fluorescent chemosensor (FCS)-based measurement method of bisphosphaonate levels using Naphta-diDPA-$2Zn^{2+}$ (NadDPA-$2Zn^{2+}$, DPA = dipycolylamine), an excellent FCS previously used for detecting PPi, was developed. By the FCS method, the concentration of bisphosphonates having no fluorophores can be determined analyzed with sufficient sensitivity. The results of this study indicate that the FCS-based measurement can be a useful method to analyze bisphosphonates in biological samples.