• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.2
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.40 no.5
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• pp.206-210
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• 2014

Objectives: To identify post-treatment prognostic factors for medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: We evaluated 54 MRONJ patients who visited the Department of Dentistry, Ajou University Hospital, from May 2007 to March 2014. Twenty-one patients were surgically managed with debridement or sequestrectomy and 33 patients were conservatively managed using antibiotics. Correlations of age, sex, stage, bisphosphonate duration and type, and drug holiday with the prognosis of MRONJ were investigated. Correlations were verified by logistic regression analysis and t-tests with a significance level of 0.05. Results: Clinical outcomes were evaluated on the basis of both clinical and radiographic findings. Twelve out of 21 surgically managed patients showed a favorable prognosis and nine patients relapsed. Thirty-one of the 33 conservatively managed patients showed no specific change in prognosis, and two patients worsened. Statistical analyses of the conservative management group did not reveal any correlation of the above factors with the prognosis of conservative management. Drug holiday was the only prognostic factor in the surgical management group (P=0.031 in logistic regression analysis, P=0.004 in t-test). Conclusion: Drug holiday is a prognostic factor in the surgical management of MRONJ. Because the drug holiday in the patients of the poor prognosis group occurred 1.5 to 4 months prior to surgical management, we recommend a drug holiday more than 4 months before surgery.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.205-213
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• 2014

The outcomes of first-generation EGFR-TKIs (Gefitnib and Erlotinib) have shown great advantages over traditional treatment strategies in patients with non-small cell lung cancer (NSCLC), but unfortunately we have to face the situation that most patients still fail to respond in the long term despite initially good control. Up to now, the mechanism of acquired resistance to EGFR-TKIs has not been fully clarified. Herein, we sought to compile the available clinical reports in the hope to better understanding the subsequent treatment choices, particularly on whether restoring after a drug holiday or switching to another EGFR-TKI is the better option after failure of one kind of EGFR-TKI.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.1
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• pp.55-56
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• 2023

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.48 no.4
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• pp.219-224
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• 2022

Objectives: There have been few studies to date on the residual effect of bisphosphonate. This study investigated the radiographic changes of mandibular cortical thickness upon bisphosphonate drug holiday. Materials and Methods: This retrospective study includes 36 patients diagnosed with MRONJ (medication-related osteonecrosis of the jaw) at Ajou University Dental Hospital in 2010-2021. All patients stopped taking bisphosphonate under consultation with the prescribing physicians. Panoramic radiographs were taken at the start of discontinuation (T₀), 12 months after (T₁), and 18 months after (T₂) discontinuation of bisphosphonate, respectively. Mental index and panoramic mandibular index were calculated using Ledgerton's method. Paired t-tests were used to analyze differences over time. Results: The difference in indices (mental index and panoramic mandibular index) between T₀ and T₁ was not statistically significant (paired t-test, P>0.05). However, the difference in these indices between T₁ and T₂ was statistically significant (paired t-test, P<0.05). Conclusion: The cortical thickness of the mandible decreased in the late stage (after 18 months) as observed by panoramic radiograph.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.4
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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 Neurosurgical Society
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• v.55 no.1
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• pp.5-11
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• 2014

Objective : We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Methods : Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Results : Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Conclusion : Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.38 no.3
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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.