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.
Bisphosphonates are widely used mainly for the treatment of osteoporosis and bone metastasis of malignancy. Since the first report of MRONJ, there have been many studies associated, however the pathogenesis of MRONJ is not yet clear. Medication-related osteonecrosis of the jaws (MRONJ) is a serious complication associated with long-term medication therapy. It is characterized by exposed necrotic bonein the jaw, which has persisted for more than 8weeks despite continuous treatment by dentist. The mechanism of development of MRONJ is still unclear and there is no definitive standard treatment for MRONJ. The purpose of this study is to investigate the jaw bone destruction mechanism of accumulated bisphosphonates, so that we can develop therapeutic method to repair the defect and stop the destruction process. The authors performed simultaneous application of PRF(Platelet rich fibrin) and BMP-2(Bone morphogenetic protein-2) to stimulate not only soft tissue healing but also osseous regeneration. Our case series demonstrate that simultaneous application of platelet rich fibrin and bone morphogenetic protein-2 can be a treatment of choice for MRONJ.
Kim, Gyeong-Mi;Moon, Seong-Yong;You, Jae-Seek;Kim, Gyeong-Yun;Oh, Ji-Su
Journal of Oral Medicine and Pain
/
v.47
no.1
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pp.1-9
/
2022
Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of antiresorptive agents and bone-modifying agents. It is of the utmost importance to know the management of the MRONJ to improve the patient's quality of life. This study comprehensively reviews the current definitions of MRONJs, and antiresorptive medications, clinical manifestation and staging, risk factors, treatment strategies, and prevention methods of MRONJ. The disease is defined as an exposure of bone and osteonecrosis of the jaw in the oral cavity for at least 8 weeks in patients taking antiresorptive drugs or antiangiogenic agents and with no history of radiotherapy treatment of the jaws. Many articles have reported risk factors associated with MRONJ such as systemic diseases, antiresorptive medication, oral infection, and poor oral hygiene. Osteonecrosis and antiresorptive medications including bisphosphonate and denosumab have been strongly associated, but the pathology of MRONJ is only limited. Hence, an effective and appropriate management and treatment for MRONJ is still to be defined. The objectives of MRONJ treatment are to minimize osteonecrosis and relieve symptoms, and many treatments are suggested from conservative treatment to marginal resection, but this remains controversial. Appropriate treatment of MRONJ remained difficult, although many studies are being covered.
This review presents an overview of some diagnostic imaging-related issues regarding medication-related osteonecrosis of the jaws(MRONJ), including imaging signs that can predict MRONJ in patients taking antiresorptive drugs, the early imaging features of MRONJ, the relationship between the presence or absence of bone exposure and imaging features, and differences in imaging features by stage, between advanced MRONJ and conventional osteomyelitis, between oncologic and osteoporotic patients with MRONJ, and depending on the type of medication, method of administration, and duration of medication. The early diagnosis of MRONJ can be made by the presence of subtle imaging changes such as thickening of the lamina dura or cortical bone, not by the presence of bone exposure. Most of the imaging features are relatively non-specific, and each patient's clinical findings and history should be referenced. Oral and maxillofacial radiologists and dentists should closely monitor plain radiographs of patients taking antiresorptive/antiangiogenic drugs.
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.46
no.1
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pp.78-83
/
2020
Objectives: The discontinuation of bisphosphonate (BP) treatment before tooth extraction may induce medication-related osteonecrosis of the jaw (MRONJ). Whether the long-term discontinuation of BP treatment before tooth extraction affects the risk of developing MRONJ after tooth extraction or whether extended drug holidays induce systemic side effects remains unclear. The present study assessed the incidence of MRONJ among patients who underwent tooth extraction and did not discontinue BP therapy prior to the procedure. Materials and Methods: Patients were classified according to whether or not they discontinued BP therapy before tooth extraction. Differences in the incidence of MRONJ after tooth extraction were compared between the two groups using the chi-squared test. Results: The BP-continuation (BPC) and BP-discontinuation (BPDC) groups included 179 and 286 patients, respectively. One patient in the BPC group and no patients in the BPDC group developed MRONJ (P=0.385). The patients in the BPDC group stopped receiving BP therapy at a mean of 39.0±35.5 months prior to tooth extraction. Conclusion: The possibility of pre-existing MRONJ in the extraction area must be considered during the extraction procedure. Routine discontinuation of BP medications for several months before the extraction procedure should be carefully considered, as evidence of its efficacy in reducing the development of post-extraction MRONJ is limited.
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.
Purpose: To present characteristic findings of Tc-99m hydroxymethylene diphosphonate (HMDP) scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging for osteonecrosis in the mandible, especially osteoradionecrosis(ORN) and medication-related osteonecrosis of the jaw(MRONJ). Materials and Methods: Thirteen patients with MRONJ and 7 patients with ORN in the mandible underwent Tc-99m HMDP scintigraphy, CT, and MR imaging (T1-weighted images[T1WI], T2-weighted images[T2WI], short inversion time inversion recovery images[STIR]), diffusion-weighted images[DWI], and apparent diffusion coefficient [ADC] mapping). The associations of scintigraphy, CT, and MR imaging findings with MRONJ and ORN were analyzed using the chi-square test with the Pearson exact test. Results: Thirteen patients with MRONJ and 7 patients with ORN in the mandible showed low signal intensity on T1WI and ADC mapping, high signal intensity on STIR and DWI, and increased uptake on scintigraphy. Periosteal bone proliferation on CT was observed in 69.2% of patients with MRONJ(9 of 13) versus 14.3% of patients with ORN(1 of 7)(P=0.019). Conclusion: This study presented characteristic imaging findings of MRONJ and ORN on scintigraphy, CT, and MR imaging. Our results suggest that CT can be effective for detecting MRONJ and ORN.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.45
no.2
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pp.108-115
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2019
Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a well-known side effect of certain drugs that are used to influence bone metabolism to treat osteometabolic disease or cancers. The purpose of our study was to investigate how high-concentration and low-concentration bisphosphonate (BP) intake affects the disease severity. Materials and Methods: Data collected from the medical records of 52 patients treated with BPs, antiresorptive, antiangiogenic drugs and diagnosed with MRONJ were included in this study. Age, sex, type of systemic disease, type of drug, duration of drug treatment, jaw area with MRONJ, drug administration protocol, and MRONJ clinical and radiological findings were obtained. Patients were divided into two groups: anti-neoplastic (Group I, n=23) and anti-osteoporotic (Group II, n=29). Statistical evaluations were performed using the IBM SPSS ver. 21.0 program. Results: In both groups, more females had MRONJ. MRONJ was found in the mandibles of 30 patients (Group I, n=14; Group II, n=16). When we classified patients according to the American Association of Oral and Maxillofacial Surgeons staging system, significant differences were seen between groups (${\chi}^2=12.23$, P<0.01). More patients with advanced stage (stage 2-3) MRONJ were found in Group I (60.9%). Conclusion: According to our results, high-concentration BP intake, age and duration of drug intake increased disease severity.
Purpose: The purpose of this study was to evaluate the cone-beam computed tomographic (CBCT) imaging and histopathological characteristics of osteoradionecrosis(ORN) and medication-related osteonecrosis of the jaw(MRONJ). Materials and Methods: Ten surgical specimens from segmental mandibulectomy (3 ORN and 7 MRONJ) were analyzed using CBCT. The CBCT parameters were as follows: high-resolution mode (tube voltage, 90.0 kV; tube current, 4.00 mA; rotation time, 16.8 s; field of view, 56 mm×56 mm; thickness, 0.099 mm). Histopathological characteristics were evaluated using histological slides of the surgical specimens. The Pearson chi-square test was used to compare ORN and MRONJ in terms of CBCT findings(internal texture, sequestrum, periosteal reaction and cortical perforation) and histopathological characteristics(necrotic bone, inflammatory cells, reactive bone formation, bacteria, Actinomyces, and osteoclasts). A P value less than 0.05 was considered to indicate statistical significance. Results: MRONJ showed periosteal reaction on CBCT more frequently than ORN (7 of 7 [100%] vs. 0 of 3 [0%], P<0.05). Regarding histopathological characteristics, MRONJ showed osteoclasts more frequently than ORN (6 of 7 [85.7%] vs. 0 of 3 [0%], P<0.05). Conclusion: This study evaluated the CBCT imaging and histopathological characteristics of ORN and MRONJ, and the findings suggest that CBCT could be useful for the evaluation of ORN and MRONJ.
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