• 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.42 no.5
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• pp.271-277
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• 2016

Objectives: The objective of this study was to retrospectively investigate the association of diseases having an influence on inhibition of angiogenesis such as hypertension, diabetes mellitus type II, hypercholesterolemia, and rheumatoid arthritis (RA) with the development of osteonecrosis of the jaws. Materials and Methods: The 135 patients were allocated into 4 groups of bisphosphonate-related osteonecrosis of the jaw (BRONJ) group (1A); non-BRONJ group (1B); osteonecrosis of the jaw (ONJ) group (2A); and control group (2B), according to histologic results and use of bisphosphonate. This retrospective study was conducted with patients who were treated in one institute from 2012 to 2013. Fisher's exact test and logistic regression analysis were used to analyze the odds ratios of diseases having an influence on inhibition of angiogenesis for development of ONJ. Results: The effects of diabetes and hypertension were not statistically significant on development of ONJ. When not considering bisphosphonate use, RA exhibited a high odds ratio of 3.23 (P=0.094), while hyperlipidemia showed an odds ratio of 2.10 (P=0.144) for development of ONJ. More than one disease that had an influence on inhibition of angiogenesis showed a statistically significant odds ratio of 2.54 (P=0.012) for development of ONJ. Conclusion: Patients without diseases having an influence on inhibition of angiogenesis were at less risk for developing ONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.1
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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.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.5
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• pp.478-483
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• 2010

Bisphosphonates are synthetic analogue and have high affinity on bone remodeling site. Since they have a long half-reduction time, they accumulate at bone and act for a long time. They are widely used in osteo-porosis derived from imflammatory bowel disease or postmenopausal osteoporosis patient for bone mineral density improvement. In addition, they neutralize hypercalcemia owing to bone metastasis of malignancy. However, a jaw bone necrosis was recently reported in some patients who have taken bisphosphonates for a long time. It is called Bisphosphonate Related Osteonecrosis of Jaws (BRONJ). It can come spontaneous-ly, but more often after oral surgery including tooth extraction. In this case, a 80-year-old woman was treated with bisphosphonate (sodium alendronate) for 2 years to improve bone mineral density. She had her left lower second molar tooth extracted at local clinic. After extraction, she had inflammatory symptoms like a pain, a cheek swelling, and a discharge of pus. She was referred to our clinic for treatment. We treated meticulously from dressing to surgery. After following up about 1.5 years, the jaw lesion was successfully healed. So we report this case.

• 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 Periodontal and Implant Science
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• v.51 no.4
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• pp.264-275
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• 2021

Purpose: Periodontitis is considered a local risk factor for medication-related osteonecrosis of the jaws (MRONJ). However, little is known about the progression of periodontitis in the presence of zoledronic acid (ZOL). The aim of this study was to evaluate the effects of the systemic use of ZOL on the progression of experimental periodontitis (EP) in rats, as ZOL could modulate the progression of periodontitis and concomitantly cause MRONJ in individuals with periodontitis. Methods: Forty-eight male Wistar rats were randomly distributed in 6 groups (n=8 each). To induce EP, ligatures were placed around the right first mandibular molars. Three groups were treated with ZOL (0.15 mg/kg/week, intraperitoneal), and 3 with 0.9% saline solution (controls). In the ZOL/Lig30 and ZOL/Lig 15 groups, after 4 weeks of treatment with ZOL, EP was induced and euthanasia was performed after 30 and 15 days of EP induction, respectively. In both groups, the animals continued to receive ZOL after EP until the end of the experiment. In the Lig/ZOL group, EP was induced first, and 15 days later, ZOL was administered for 8 weeks, with euthanasia 1 week after the last dose. After euthanasia, the mandibles were evaluated using micro-computed microtomography (micro-CT) and histomorphometry. Bone loss was measured, and the presence of osteonecrosis was evaluated histologically. The data were evaluated using the Student t-test and the Mann-Whitney test, with a significance level of 5%. Results: In the Lig/ZOL group, micro-CT revealed less alveolar bone resorption in the distal root (P<0.01) than in the control group (Lig/Con). Histomorphometric analysis confirmed less alveolar bone resorption in the Lig/ZOL group (P=0.001). Histologically, osteonecrosis was more common in the ZOL groups. Conclusion: ZOL decreased alveolar bone resorption in rats with EP. However, it presented a higher risk for MRONJ.

• The Journal of the Korean dental association
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• v.48 no.7
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• pp.538-546
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• 2010

Dental surgical procedures are potentially stress-inducing to not only patients but clinicians especially in case of medically compromised patients. The body response to dental stress involves the cardiovascular, respiratory and the endocrine system. To minimize the stress to the medically compromised patients, the stress reduction protocols should be established. The protocols include (1) Recognize the patient's degree of medical risk (2) Medical consultation before dental therapy (3) Schedule the patient's appointment in the morning (4) Monitor and record preoperative, perioperative and postoperative vital signs (5) Intra-venous sedation during surgical procedures (6) Adequate pain control during therapy (7) Short length of appointment time (8) Contact the patients on the same day. Two cases of Bisphosphonate-related osteonecrosis of the jaws were analyzed. There were 2 women, and the mean age was 70 years (range, 64~74 years). both are medically compromised, with steroids. Both patients were taking an oral bisphosphonate for several years. BRONJ is defined as an area of exposed bone of more than 8 weeks - duration in a patient taking a bisphosphonate for bone disease. Bisphosphonates have been widely prescribed over the last decade for a range of bone diseases, mainly intravenously for bone cancers and orally for osteoporosis. Although it is still controversial as to precisely how the bisphosphonates work, generally it is accepted that they prevent osteoclast action, with consequent cessation of osteoblast activity, so that the bone turnover is markedly reduced or ceased. The aim of this study is to informed the clinicians how to prepare and recognize in case of the BRONJ with medically compromised patients.