• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.1
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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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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• v.35 no.3
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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.

• Journal of Dental Rehabilitation and Applied Science
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• v.27 no.4
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• pp.449-454
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• 2011

Recently, jawbone osteonecrosis has been largely reported as a potential adverse effect of bisphosphonate (BP)administration. Currently available published incidence data for BRONJ are based on retrospective studies and estimates of cumulative incidence range from 0.8 to 12%. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60-70% of cases are preceded by a dental surgical procedure. The signs and symptoms that may occur before the appearance of clinical evident osteonecrosis include changes in the health of periodontal tissues, non-healing mucosal ulcers, loose teeth and unexplained soft-tissue infection. Tooth extraction as a precipitating event is a common observation. The significant benefits that bisphosphonates offer to patients clearly surpass the risk of potential side effects; however, any patient for whom prolonged bisphosphonate therapy is indicated, should be provided with preventive dental care in order to minimize the risk of developing this severe condition.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.3
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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.

• Imaging Science in Dentistry
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• v.47 no.1
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• pp.45-50
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• 2017

Purpose: The aim of this study was to investigate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after tooth extraction in patients with osteoporosis on oral bisphosphonates in Korea and to evaluate local factors affecting the development of BRONJ. Materials and Methods: The clinical records of 320 patients who underwent dental extraction while receiving oral bisphosphonates were reviewed. All patients had a healing period of more than 6 months following the extractions. Each patient's clinical record was used to assess the incidence of BRONJ; if BRONJ occurred, a further radiographic investigation was carried out to obtain a more definitive diagnosis. Various local factors including age, gender, extraction site, drug type, duration of administration, and C-terminal telopeptide (CTx) level were retrieved from the patients' clinical records for evaluating their effect on the incidence of BRONJ. Results: Among the 320 osteoporotic patients who underwent tooth extraction, 11 developed BRONJ, reflecting an incidence rate of 3.44%. Out of the local factors that may affect the incidence of BRONJ, gender, drug type, and CTx level showed no statistically significant effects, while statistically significant associations were found for age, extraction site, and duration of administration. The incidence of BRONJ increased with age, was greater in the mandible than the maxilla, and was associated with a duration of administration of more than 3 years. Conclusion: Tooth extraction in patients on oral bisphosphonates requires careful consideration of their age, the extraction site, and the duration of administration, and close postoperative follow-up should be carried out to facilitate effective early management.

• Imaging Science in Dentistry
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• v.53 no.2
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• pp.109-115
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• 2023

Purpose: The aim of this study was to evaluate changes in the trabecular bone through texture analysis and compare the texture analysis characteristics of different areas in patients with medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: Cone-beam computed tomographic images of 16 patients diagnosed with MRONJ were used. In sagittal images, 3 regions were chosen: active osteonecrosis(AO); intermediate tissue (IT), which presented a zone of apparently healthy tissue adjacent to the AO area; and healthy bone tissue (HT) (control area). Texture analysis was performed evaluating 7 parameters: secondary angular momentum, contrast, correlation, sum of squares, inverse moment of difference, sum of entropies, and entropy. Data were analyzed using the Kruskal-Wallis test with a significance level of 5%. Results: Comparing the areas of AO, IT, and HT, significant differences (P<0.05) were observed. The IT and AO area images showed higher values for parameters such as contrast, entropy, and secondary angular momentum than the HT area, indicating greater disorder in these tissues. Conclusion: Through texture analysis, changes in the bone pattern could be observed in areas of osteonecrosis. The texture analysis demonstrated that areas visually identified and classified as IT still had necrotic tissue, thereby increasing the accuracy of delimiting the real extension of MRONJ.

• The Journal of the Korean dental association
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• v.53 no.2
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• pp.120-131
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• 2015

Objective: The purpose of this study is to compare the surgical treatment with conservative treatment and to evaluate the effectiveness of drug-holiday in bisphosphonate related osteonecrosis of the jaw (BRONJ) patients who were diagnosed as stage 2. Patients and Method: From January 2012 to October 2014, seventy-two patients who visit to Pusan National University of Dental Hospital were diagnosed as stage 2 of BRONJ. All the patients had taken computed tomography(CT) and panoramic radiography. The surgical treatment including sequestrectomy of necrotic bone and curettage of soft tissue around the sequestrum were performed to fifty patients. Twenty-two patients underwent conservative treatment such as antibiotics medications, mouth rinsing and follow up checking for every two weeks. Prognosis of treatment was classified into 3 groups - response, unresponse, and worsens - according to clinical, radiographic symptoms. P-value less than 0.05 were regarded as significant. Results: In surgery group, forty-five patients (90%) were healed without recurrence or any complication and five patients (10%) showed the wound dehiscence or infection. In conservative treatment group, fifteen patients (68.2%) were healed without any complication, four patients (18.2%) did not show improvement and three(4.2%) patients$^{\circ}{\emptyset}$ symptoms increased. P-value among groups was 0.014. Evaluation of preoperative drug-holiday in surgery group did not show the effectiveness(p=0.478). Conclusion: Statistically, the prognosis of patients with stage 2 BRONJ treated with surgery was significantly better than conservative treatment. There was no statistical difference for the preoperative drug-holiday.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.4
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• pp.174-181
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• 2018

Objectives: The number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing, but treatment remains controversial. Published papers and systematic reviews have suggested that surgical treatment is effective in patients with MRONJ. The purpose of this study was to determine whether preoperative University of Connecticut Osteonecrosis Numerical Scale (UCONNS), other serologic biomarkers, and size of necrosis are prognostic factors for outcome of surgical treatment in MRONJ. Materials and Methods: From January 2008 to December 2016, 65 patients diagnosed with MRONJ at the Department of Oral and Maxillofacial Surgery in College of Dentistry, Dankook University who required hospitalization and surgical treatment were investigated. Patient information, systemic factors, and UCONNS were investigated. In addition, several serologic values were examined through blood tests one week before surgery. The size of osteolysis was measured by panoramic view and cone-beam computed tomography in all patients. With this information, multivariate logistic regression analysis with backward elimination was used to examine factors affecting postoperative outcome. Results: In multivariate logistic analysis, higher UCONNS, higher C-reactive protein (CRP), larger size of osteolysis, and lower serum alkaline phosphate were associated with higher incidence of incomplete recovery after operation. This shows that UCONNS, CRP, serum alkaline phosphate, and size of osteolysis were statistically significant as factors for predicting postoperative prognosis. Conclusion: This study demonstrated that CRP, UCONNS, serum alkaline phosphate, and size of osteolysis were statistically significant factors in predicting the prognosis of surgical outcome of MRONJ. Among these factors, UCONNS can predict the prognosis of MRONJ surgery as a scale that includes various influencing factors, and UCONNS should be used first as a predictor. More aggressive surgical treatment and more definite surgical margins are needed when the prognosis is poor.