• Maxillofacial Plastic and Reconstructive Surgery
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• v.39
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• pp.1.1-1.7
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• 2017

Background: Multiple myeloma (MM) is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Bisphosphonates (BP) are used as supportive therapy in the management of MM. This study aimed to analyze the incidence, risk factors, and clinical outcomes of medication-related necrosis of the jaw (MRONJ) in MM patients. Methods: One hundred thirty MM patients who had previous dental evaluations were retrospectively reviewed. Based on several findings, we applied the staging and treatment strategies on MRONJ. We analyzed gender, age, type of BP, incidence, and local etiological factors and assessed the relationship between these factors and the clinical findings at the first oral examination. Results: MRONJ was found in nine male patients (6.9%). The mean patient age was 62.2 years. The median BP administration time was 19 months. Seven patients were treated with a combination of IV zoledronate and pamidronate, and two patients received single-agent therapy. The lesions were predominantly located in the mandible (n = 8), and the most common predisposing dental factor was a history of prior extraction (n = 6). Half of the MRONJ were related to diseases found on the initial dental screen. Patients with MRONJ were treated with infection control and antibiotic therapy. When comparing between the MRONJ stage and each factor (sign, location, etiologic factor, BP type, treatment, and outcome), there were no significant differences between stages, except for between the stage and sign (with or without purulence). Conclusions: For prevention of MRONJ, we recommend routine dental examinations and treatment prior to starting BP therapy.

• 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.1-8
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• 2011

Introduction: The utility of the C-terminal cross-linking telopeptide test (CTX) as a method for staging Bisphosphonate-related osteonecrosis of the jaws (BRONJ) and its healing process was examined. Materials and Methods: A total 19 patients who were diagnosed with BRONJ underwent a fasted morning CTX test, were enrolled in this study. The serum CTX values ranged from 50 to 630 pg/mL (mean 60). The risk assessment was rated according to the CTX values of the individual patient (minimal risk, ${\geq}$ 150 pg/mL, moderate, 100 to 150 pg/mL, high, ${\leq}$100 pg/mL). The BRONJ scores were then calculated according to the number of BRONJ lesions and their stage. The operation was done as soon as possible, regardless of BORNJ stage. Results: The mean duration of bisphosphonate therapy was 4.1 years. Of the 19 patients, 15, 2 ans 2 received alendronate, risedronate and zoledronate, respecively. Of the 19 patients who underwent a sequestrectomy, saucerization and smoothing, 15 healed after the initial surgery, 1 patient healed after one more surgical procedure, 3 patients did not heal completely but showed improvement in symptoms. Therefore, 17 out of the 19 patients healed completely with complete mucosal coverage and the elimination of pain. The risk assessment using the CTX value and disease severity were not correlated (r=-0.264, P=0.275). In addition, the risk assessment using CTX value and healing after surgery were not correlated (r=-0.147, P=0.547). Conclusion: The serum CTX should be considered carefully by clinicians as part of overall management. Early surgical intervention is of benefit in the treatment of stage II BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.2
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• pp.75-85
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• 2023

Objectives: Suspending bisphosphonates (BPs) to reduce the risk and severity of medication-related osteonecrosis of the jaw (MRONJ) remains controversial. In this study, we quantitatively evaluated the clinical significance of BP suspension before surgery in osteoporosis patients with MRONJ. Materials and Methods: We analyzed 24 osteoporosis patients with MRONJ who were treated from 2012 to 2020 at Seoul National University Dental Hospital and compared the treatment outcomes of those who suspended BPs with those who did not. The number of surgical interventions, follow-up panoramic radiographs for relative bone density measurement, and laboratory blood tests including white blood cells, erythrocyte sedimentation rate, absolute neutrophil count, hemoglobin, hematocrit, and alkaline phosphatase were analyzed. ANOVA, Student's t-test, and Mann-Whitney U tests were used to compare results. Fisher's exact test was used to discover the association between treatment outcome and BP suspension, and Pearson's correlation test was used to measure the statistical relationship between the changes in serum inflammatory markers. Results: The number of interventions was significantly higher in the non-drug suspension group due to recurrence (P<0.05). The relative bone density in patients who suspended BPs was significantly different over time (P<0.05), with the highest density at one-year follow-up. Fisher's exact test shows an association between successful treatment outcomes and BP suspension. The alkaline phosphatase and erythrocyte sedimentation rate levels decreased significantly in the BP-suspended group, and a positive correlation was found between these elevated markers. Conclusion: A significant increase in bone density throughout follow-up and a lower number of interventions were found in the BP suspension group compared to the non-drug suspension group. Also, BP suspension decreased inflammatory markers in the serum after surgery, resulting in good treatment outcomes. BP suspension is a prognostic factor for MRONJ and should be implemented before surgery.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.17.1-17.7
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• 2018

Background: Bisphosphonate (BP) has the ability to thicken the cortical bone. In addition, it has been reported that the cortical bone thickened by BP has relation to the medication-related osteonecrosis of the jaw (MRONJ). Therefore, the objective of this article is to analyze the ratio as well as thickness of cortical bone in the mandible using computed tomography (CT) and to evaluate it as the predictive factor of MRONJ. Methods: The thickness of the cortical bone was measured on a paraxial view of the CT showing the mental foramen in 95 patients: 33 patients with MRONJ (3 males, 30 females), 30 patients taking BP without MRONJ (2 males, 28 females), and 32 controls (9 males, 28 females). Also, the ratios of the cortical bone to the total bone were obtained using the measured values. Based on these results, we compared the difference of mandibular cortical bone ratio between the three groups. Results: The average cortical bone thickness was measured as 3.81 mm in patients with MRONJ, 3.39 mm in patients taking BP without MRONJ, and 3.23 mm in controls. There was only a significant difference between patients with MRONJ and controls (P < 0.05). On the other hand, the average mandibular cortical bone ratio was measured as 37.9% in patients with MRONJ, 27.9% in patients taking BP without MRONJ, and 23.3% in controls. There was a significant difference between all groups (P < 0.05). Conclusion: The mandibular cortical bone ratio is large in order of patients with MRONJ, patients taking BP without MRONJ, and controls. This result suggests that the mandibular cortical bone ratio would be very useful to predict the development of MRONJ.

• The Journal of the Korean dental association
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• v.52 no.4
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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.

• Childhood Kidney Diseases
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• v.18 no.2
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• pp.92-97
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• 2014

Purpose: Bisphosphonates are widely used for the management steroid-induced osteoporosis (SIO) in children. With the increasing use of bisphosphonates, there have been reports of abnormal radiological findings in the growing skeleton. Therefore, their use in pediatric patients remains controversial. The present study was conducted to evaluate the long-term follow-up radiographic features, particularly metaphyseal sclerotic lines, in children who receive pamidronate therapy for nephropathy. Methods: Twenty-four children with nephropathy treated with oral calcium and pamidronate (mean duration, 9 months; dose, 100 mg daily), were evaluated retrospectively. All patients had SIO secondary to chronic glucocorticoid therapy for treating nephropathy. Long bone radiographic imaging was performed before treatment with pamidronate, and at follow-up, several years later. Physeal growth rates were estimated by measuring the distance that the sclerotic lines moved on the radiographs during the corresponding time intervals. Results: The mean follow-up period was 138 months. Long bone radiographs showed well-defined sclerotic lines at the metaphyseal ends, progressively moving from the physeal plate to the diaphysis, in all patients. The mean rate of movement of the sclerotic line was 6.21 mm per year. In 12 patients, the lines disappeared. The mean rate of growth in height was 7.33 cm per year. Conclusions: Results of long-term follow-up suggest that the metaphyseal sclerotic lines associated with pamidronate treatment tend to disappear without affecting overall skeletal growth. Bisphosphonate treatment for SIO in children with nephropathy seems to be safe, although further studies in larger number of patients are needed.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.43-50
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• 2004

Background : Steroid-induced osteoporosis(SIO) is one of the serious complications of long-term steroid therapy, especially in growing children. Recently bisphosphonates have been used to treat or prevent SIO in adult, which is rare in children with glomerular diseases. We studied the effect of pamidronate on SIO using dual energy X-ray absorptiometry and biochemical markers of bone turnover. Methods : Forty four children receiving moderate-to-high doses of steroids were enrolled. They had no history of bone, liver, or endocrine disease. Patients were stratified by their baseline bone mineral density(BMD) findings. All patients received corticosteroids for 3 month and oral calcium supplementation(500 mg/day) daily. Among them, 28 patients were treated with placebo and 16 were treated with pamidronate(125 mg) for 3 months. Blood chemistry and bone mineral density(BMD) were measured at baseline, and 3months. In addition, parathyroid hormone(PTH), serum osteocalcin, and urinary dipyridinoline levels were evaluated. Results : In overall population, the mean lumbar spine BMD decreased from $0.754{\pm}0.211(g/cm^2)$ to $0.728{\pm}0.208(g/cm^2)$ in the placebo group(P<0.05) and increased from $0.652{\pm}0.194(g/cm^2)$ to $0.658{\pm}0.226(g/cm^2)$ in the pamidronate group(P>0.05). Conclusion : Pamidronate appears to be effective in preventing SIO in children with glomerular diseases requiring long-term steroids therapy. Further careful observation and follow-up might be needed for children receiving bisphosphonates such as pamidronate.

• 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 Dental Rehabilitation and Applied Science
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• v.32 no.2
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• pp.93-101
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• 2016

The average life expectancy has been increased, so the proportion of elderly patients that visit to the dental clinic for prosthetic restoration has increased. Elderly patients have various chronic diseases. Recent trends show an increase of osteoporosis in elderly patients, and thus, the number of osteoporosis patients is expected to escalate. Currently, the most widely used drug for osteoporosis is bisphosphonate. However, osteonecrosis of the jaw has been reported as a side effect derived from longterm oral administration or injection treatment of the drug. Surgical dental treatment was the main cause of medication related osteonecrosis of the jaw (MRONJ). As MRONJ is very difficult to cure, it is important to take preventive measures. Surgical operation may be needed for the mouth preparation before prosthetic restoration. For successful treatment, the dentist should have a full understanding of osteoporosis and show a continued interest toward this disease for careful management.