• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.4
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• pp.291-302
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• 2010

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of Bisphosphonates (BPs) use. These days, oral bisphosphonates are normally prescribed to treat osteoporosis. Intravenous BPs are used extensively to treat osteolytic bone lesions related to multiplemyeloma and bone metastasis of solid cancers, breast cancer or prostate cancer. As the prescription of BPs is universalized and the number of people treated with BPs is increasing, an accurate understanding and proper management of BRONJ are required. The aim of this study was to improve the clinicians' understanding of BRONJ by reviewing the literature. To achieve this, this paper introduces case reports as well as the current concept of BRONJ based on the 2009 updates by American Association of Oral and Maxillofacial (AAOMS) including the definition, epidemiology, etiology, diagnosis, treatment and prevention of BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.3
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• pp.135-141
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• 2023

Objectives: This study aimed to develop and validate machine learning (ML) models using H₂O-AutoML, an automated ML program, for predicting medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis undergoing tooth extraction or implantation. Patients and Methods: We conducted a retrospective chart review of 340 patients who visited Dankook University Dental Hospital between January 2019 and June 2022 who met the following inclusion criteria: female, age ≥55 years, osteoporosis treated with antiresorptive therapy, and recent dental extraction or implantation. We considered medication administration and duration, demographics, and systemic factors (age and medical history). Local factors, such as surgical method, number of operated teeth, and operation area, were also included. Six algorithms were used to generate the MRONJ prediction model. Results: Gradient boosting demonstrated the best diagnostic accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.8283. Validation with the test dataset yielded a stable AUC of 0.7526. Variable importance analysis identified duration of medication as the most important variable, followed by age, number of teeth operated, and operation site. Conclusion: ML models can help predict MRONJ occurrence in patients with osteoporosis undergoing tooth extraction or implantation based on questionnaire data acquired at the first visit.

• Imaging Science in Dentistry
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• v.45 no.3
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• pp.199-203
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• 2015

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.38
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• pp.6.1-6.8
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• 2016

Background: Intravenous bisphosphonates have been used in metastatic breast cancer patients to reduce pathologic bone fracture and bone pain. However, necrosis of the jaw has been reported in those who received intravenous bisphosphonates. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is caused by dental extraction, dental implant surgery, and denture wearing; however, it occurs spontaneously. The purpose of this study was to report BRONJ in metastatic breast cancer patients. Methods: Consecutive 25 female patients were referred from the Department of Oncology from 2008 to 2014 for jaw bone discomfort. Staging of breast cancer, history of bisphosphonate infusion, etiology of BRONJ, and treatment results were reviewed. Average age of the patients was 55.4 years old (38-74). Twelve maxillae and 16 mandibles were involved. Conservative treatments such as irrigation, antibiotic medication, analgesics, and oral gargle were applied for all patients for the initial treatment. Patients who had sequestrum underwent debridement and primary closure. Results: The etiologies of BRONJ were dental extraction (19 cases), dental implant (2 cases), and endodontic treatment (1 case). However, three patients did not have any risk factors to cause BRONJ. Three patients died of progression of metastasis during follow-up periods. Surgical debridement was performed in 21 patients with success in 18 patients. Three patients showed recurred bone exposure and infection after operation. Conclusions: Prevention of the BRONJ is critical in metastatic breast cancer patients. Conservative treatment to reduce pain, discomfort, and infection is recommended for the initial therapy. However, if there is a sequestrum, surgical debridement and primary closure is the key to treat the BRONJ.

• 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.

• Imaging Science in Dentistry
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• v.49 no.1
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• pp.53-58
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• 2019

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.47 no.2
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• pp.65-75
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• 2021

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.2
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• pp.57-61
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• 2014

Bisphosphonate is used widely for osteoporosis treatment, but a rising concern is the risk of osteonecrosis after long-term bisphosphonate use. Such cases are increasing, suggesting a need for research to prevent and treat bisphosphonate-related osteonecrosis of jaws. A 63-year-old female took bisphosphonate (Fosamax$^{(R)}$) for four years for treatment of osteoporosis and stopped medication two months ago because of unhealed wound. She was treated with marginal mandibulectomy maintaining the inferior border, and a metal plate was placed to prevent mandible fracture. Four months after the mandibulectomy, mandible reconstruction surgery using iliac bone and allograft was done. Six months after reconstruction, implant placement and treatment with an overdenture was done without complications. This study presents a case with a successful result.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.1
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• pp.3-8
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• 2019

Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.

• The Journal of the Korean dental association
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• v.49 no.7
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• pp.389-397
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• 2011

Bisphosphonate inhibits the function of osteoclast, so they are widely used for multiple myeloma, Paget's disease, metastatic malignant bone disease, and severe osteoporosis. This drug is very effective for preventing severe complication of osteoporosis, some unpredictable complication occurred such as esophageal malignancy, atypical fracture of femur, and osteonecrosis of the jaw. Bisphosphonate related osteonecrosis of the jaw (BRONJ) is closely related with invasive, open bone surgery like tooth extraction. BRONJ associated with dental implant is rare, however, as the use of bisphosphonate increase, BRONJ cases with dental implant are increasing. In this article, we will describe the considerations during dental implant treatment for patient under bisphosphonate therapy.