• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권5호
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• pp.456-462
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• 2007

Since the first description of bisphosphonate related osteonecrosis of the jaw (BRONJ) in 2002, the number of report on the disease has rapidly been increasing. Now, BRONJ is considered as a new entity, which is emerging problem in oral and maxillofacial surgery. Bisphosphonates (BPs) can be categorized into 2 groups: nitrogen-containing and non-nitrogen containing, and nitrogen-containing BPs are considered to have more efficacy and toxicity possibly. It is unusual for osteonecrosis to occur in the maxilla but BRONJ is found in both the mandible and the maxilla, which is one of the special features of BRONJ compared with common infectious osteomyelitis of the jaws. Intravenous BPs are usually more likely to cause BRONJ than oral BPs which are frequently prescribed for osteoporosis and osteopenia. Nonetheless, the use of intravenous BPs cannot be prevented because of systemic condition of the patients. Although it is rare that oral BPs cause BRONJ in osteoporosis/osteopenia patients, we should be aware of BRONJ since the population of the patients is exceedingly increasing with the prolonging of life expectancy. So, we'd like to enlighten upon the problems and solutions of BRONJ.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제38권
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• pp.6.1-6.8
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• 2016

Background: Intravenous bisphosphonates have been used in metastatic breast cancer patients to reduce pathologic bone fracture and bone pain. However, necrosis of the jaw has been reported in those who received intravenous bisphosphonates. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is caused by dental extraction, dental implant surgery, and denture wearing; however, it occurs spontaneously. The purpose of this study was to report BRONJ in metastatic breast cancer patients. Methods: Consecutive 25 female patients were referred from the Department of Oncology from 2008 to 2014 for jaw bone discomfort. Staging of breast cancer, history of bisphosphonate infusion, etiology of BRONJ, and treatment results were reviewed. Average age of the patients was 55.4 years old (38-74). Twelve maxillae and 16 mandibles were involved. Conservative treatments such as irrigation, antibiotic medication, analgesics, and oral gargle were applied for all patients for the initial treatment. Patients who had sequestrum underwent debridement and primary closure. Results: The etiologies of BRONJ were dental extraction (19 cases), dental implant (2 cases), and endodontic treatment (1 case). However, three patients did not have any risk factors to cause BRONJ. Three patients died of progression of metastasis during follow-up periods. Surgical debridement was performed in 21 patients with success in 18 patients. Three patients showed recurred bone exposure and infection after operation. Conclusions: Prevention of the BRONJ is critical in metastatic breast cancer patients. Conservative treatment to reduce pain, discomfort, and infection is recommended for the initial therapy. However, if there is a sequestrum, surgical debridement and primary closure is the key to treat the BRONJ.

• 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.

• Imaging Science in Dentistry
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• 제45권3호
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제49권2호
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• pp.68-74
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• 2023

Objectives: Drug holidays are suggested to reduce the formation of osteonecrosis in patients under intravenous (IV) bisphosphonates (BPs) therapy. The objectives of this study are to evaluate the incidence of medication-related osteonecrosis of the jaw (MRONJ) following tooth extraction in cancer patients using IV BP, and to assess the effect of drug holiday on the development of MRONJ. Patients and Methods: A manuel search of the patient folders of Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hacettepe University was undertaken to identify cancer patients who used IV BPs and had at least one tooth extraction between 2012 and 2022. Patents' age, sex, systemic condition, the type of BP used, duration of BP used, number of tooth extraction, duration of drug holiday, localization of tooth extraction and incidence of MRONJ were recorded. Results: One hundred nine teeth were removed from 57 jaws in 51 patients. All tooth extractions were performed under perioperative antibiotic prophylaxis and with primary wound closure. The incidence of MRONJ was 5.3%. Stage 1 MRONJ developed in 3 patients (only one had a drug holiday). The median duration of drug holiday was 2 months. No significant difference between the patients with and without a drug holiday and MRONJ development was found (P=0.315). The mean age of patients developed MRONJ was 40.33±8.08 years. A statistically significant difference was found between age and MRONJ development (P=0.002). Conclusion: The effect of a short-term drug holiday on the development of MRONJ may be limited because BPs remain in bone tissue for a long time. Drug holidays should be applied with the approval of an oncologist with other preventive measurements.

• Asian-Australasian Journal of Animal Sciences
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• 제5권2호
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• pp.303-308
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• 1992

Three female sheep were daily administered a pyrophosphate analogue, disodium 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) at the level of 4 mg/kg body weight. HEBP largely suppressed bone resorption, which was indicated by the reduction in plasma free hydroxyproline concentration and in calcium mobilization rate during the intravenous infusion of disodium ethylenediaminetetraacetate (EDTA). Contrary to the suppression of bone resorption, plasma total-calcium, magnesium and phosphorus concentrations were not changed by HEBP administration. These results suggest that bone mineral crystals play a meaningless role on calcium, magnesium and phosphorus homeostasis in ruminants if they are fed adequate amounts of these minerals. Plasma magnesium and phosphorus concentrations were not significantly changed after feeding. However, plasma total-calcium was decreased after feeding in both periods and the reduction seemed to be remarkable in the HEBP-treated period. Infusion of EDTA more remarkably reduced plasma ionized calcium concentration in the HEBP-treated that in the untreated period and the recovery of ionized calcium was retarded by HEBP administration. These results suggest that calcium release from bone is necessary for maintenance of plasma calcium when animals rapidly lose calcium.

• 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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• 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.

• Clinical and Experimental Pediatrics
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• 제60권12호
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• pp.403-407
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• 2017

Purpose: Quadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients. Methods: Ten quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, $10.9{\pm}5.76years$), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5-1.0 mg/kg/day, 2 consecutive days) every 3-4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment. Results: The main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was $4.49{\pm}2.22mg/kg/yr$, and the mean treatment period was $10.8{\pm}3.32months$. The BMD z score of the lumbar spine showed a significant increase from $-4.22{\pm}1.24$ before treatment to $-2.61{\pm}1.69$ during treatment (P=0.008). Alkaline phosphatase decreased during treatment (P=0.037). Significant adverse drug reactions and new fractures were not reported. Conclusion: Low-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제47권1호
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• pp.20-24
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• 2021

Objectives: The aim of this study was to evaluate the profile of patients on antiresorptive therapies for cancer treatment and assess presence of oral lesions, oral hygiene status, and knowledge regarding medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: This was an observational cross-sectional study that evaluated patients treated with antiresorptive medication at a single cancer hospital. Clinical data were collected and oral examination was performed to assess patient oral health. Results: From July 2017 to December 2018, 90 patients were assessed; 64 were female and 26 were male, and the mean age was 61 years. The most common drug was an intravenous bisphosphonate, zoledronic acid. Among the 90 patients, 47 presented with some type of oral disease, isolated or associated. Among these 47 patients, 9 patients (10%) developed osteonecrosis. Oral hygiene was evaluated, and most patients, with or without MRONJ, presented with regular to poor condition. Regarding patient knowledge of the risks of MRONJ and the risks associated with dental surgery, 60% stated that they were not aware of the risks. Conclusion: Identifying the profile of patients and their needs facilitates not only the preventive process, but also the emergence of new therapeutic options. Our study shows that most patients are weakened both by metastatic disease and antineoplastic treatment as well as by issues associated with aging because most were over 60 years of age. Collectively, this information should be considered for management of preventive and therapeutic measures.