• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.4
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• pp.266-274
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• 2020

Objectives: Melatonin induces human stem cells, converts pre-osteoblasts to mature osteoblasts, and reduces the duration of this transition. However, melatonin itself prevents activation of osteoclasts. Here, we evaluate the role of melatonin in prevention of bisphosphonate-related osteonecrosis of the jaw. Materials and Methods: In this experimental-interventional study, 30 rats were evaluated in 3 groups. The first and second groups received saline and zoledronic acid, respectively, for 4 weeks and the third group received 4 weeks of zoledronic acid and 3 weeks of melatonin simultaneously. First-right-maxillary-molar extraction was performed for all animals, which were sacrificed after 4 weeks of recovery. The extraction sockets were examined histologically for the presence of osteonecrosis, number of osteoclasts and fibroblasts, severity of inflammation, and vascularization. Data were analyzed by chi-square, one-way ANOVA, Tukey, Kruskal-Wallis and Fisher's exact statistical tests (α=0.05). Results: Osteonecrosis was observed in 20%, 90%, and 70% of the first, second and third groups, respectively (P=0.008). The lowest number of osteoclasts and fibroblasts was seen in the third group. Conclusion: Melatonin may effectively prevent some undesirable side effects of bisphosphonates. However, further studies are required to confirm the results of this study.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.3
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• pp.174-177
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• 2013

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a disease characterized by jaw necrosis and delayed wound healing in patients who had received bisphosphonates. Buccal fat pad (BFP) can be used as a pedicled flap in the posterior region of the oral cavity. BFP pedicle flap needs simple surgical technique and it shows less donor site morbidity and aesthetic problem than other vascularized flap. BFP pedicled flap was fed by 3 arteries-facial, internal maxillary, and transverse facial artery. Osteomyelitis was generally related with poor blood supply. Thus, rich blood supply of BFP pedicle flap can have a potential advantage to BRONJ patients. In this case report, we presented 3 BRONJ patients treated by BFP pedicle flap after sequestrectomy.

• Imaging Science in Dentistry
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• v.45 no.3
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• pp.199-203
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• 2015

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.1
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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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.37
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• pp.18.1-18.7
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• 2015

Background: The aim of this study is to develop a rat model of bisphosphonates-related osteonecrosis of the jaw (BRONJ) that would be verified with clinical, radiological and histological examination, and to confirm the influence of concurrent bisphosphonates and steroids use upon the occurrence and aggravation of BRONJ. Methods: Twenty seven rats were divided into 3 groups; Saline group (I), Zoledronate group (II), Zoledronate and Dexamethasone group (III). Rats got weekly intraperitoneal injection for 4 times and extraction of left maxillary and mandibular 1st, 2nd molars were followed. Consecutive injections were performed, and blood sampling for measurements of C-terminal crosslinked telopeptide of type I collagen and tartrate-resistant acid phosphate 5b rats were performed at the time of 2, 4 and 8 weeks. And then, rats were sacrificed and evaluated clinically, radiologically and histologically. Results: 12/18 (66.6 %) of experimental group were diagnosed as BRONJ. There was no significant difference in incidence between zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll). Conclusions: Concurrent use of bisphosphonates and steroids increase incidence of BRONJ compared to saline group (l). Zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll) shows same incidence of BRONJ. Based on this study, the rat treated with bisphosphonates and steroids can be considered a novel, reliable and reproducible model to understand pathology of BRONJ.

• The Journal of Advanced Prosthodontics
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• v.5 no.4
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• pp.374-381
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• 2013

PURPOSE. The purpose of this study was to evaluate the effect of alendronates on bone remodeling around titanium implant in the maxilla of rats. MATERIALS AND METHODS. The maxillary first molars were extracted and customized-titanium implants were placed immediately in thirty male Sprague-Dawley rats. The rats were divided into experimental (bisphosphonate) group and control group. At 4 weeks after implantation, the rats in the bisphosphonate group were subcutaneously injected with alendronate three times a week for 6 weeks where as the rats in control group were injected with saline. The rats were sacrificed at 1, 2, 3, 4, or 6 weeks after starting of injection and maxillary bones were collected subsequently. Alveolar bone remodeling around the implants were evaluated by radiographic and histologic analysis. Microarray analysis and immunohistomorphologic analysis were also performed on one rat, sacrificed at 6 weeks after starting of injection, from each group. Statistical analysis was performed using repeated measures analysis of variance and independent t test at a significance level of 5%. RESULTS. There was no statistically significant difference in the bone area (%) around implant between the bisphosphonate group and the control group. However, the amount of empty lacuna was significantly increased in the bisphosphonate group, especially in the rats sacrificed at 4 weeks after starting of injection compared to that of the corresponding control group. The bisphosphonate group showed the same level of TRAP positive cell count, osteocalcin and angiopoietin 1 as the control group. CONCLUSION. Alendronate may not decrease the amount of osteoclast. However, the significantly increased amount of empty lacuna in the bisphosphonate group may explain the suppression of bone remodeling in the bisphosphonate group.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.4
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• pp.395-398
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• 2008

Bisphosphonate are a class of drugs with a chemical structure which inhibit bone resorption, actually used for metastatic bone disease, osteoporosis, Paget's disease and multiple myeloma. Significant complication associated with their use is reported recently : mandibular and maxillary osteomyelitis or osteonecrosis. So we here report our case about the patient who was diagnosed of prostate cancer in 2004 April and treated with bisphosphonate(Zoledronic acid-$Zometa^{(R)}$, Novartis Co.) intravenously every 3 to 4weeks at a dose of 4mg to prevent bone metastasis, and also, the patient who came to the hospital due to the bony exposure of mandible and pain in 2006 November and was diagnosed osteomyelitis of mandible as a result of biopsy, bone scan, PET CT examination.