• 대한치과의사협회지
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• 제52권4호
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• pp.203-217
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• 2014

Bisphosphonates are widely used in the treatment of many medical conditions, such as osteoporosis, multiple myeloma, Paget's disease, etc. However, side effect has been documented in the published data during the past years, osteonecrosis of the jaw in patients receiving long-term bisphosphonate therapy. Although pathogenesis of BRONJ(bisphophonate-related osteonecrosis of the jaw) is not yet fully understood, it is currently known to be a disease associated with suppressed bone turnover by bisphopbonate. Recent literature has indicated a similar association with nonbisphosphonate drugs used in cancer therapy including monoclonal antibodies denosumab and bevacizumab and multikinase inhibitor sunitinib. Accordingly, many studies have been carried out on the biochemical markers examination to assess the risk for BRONJ. The treatment of BRONI is reported with a review of the relevant literature. However, there is still a controversial discussion about the adequate treatment. It is necessary to accumulate further studies in order to establish more useful biochemical markers and effective treatment for BRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제44권5호
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• pp.225-231
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• 2018

Objectives: The purpose of this study was to investigate the demographic and clinical characteristics of patients with medication-related osteonecrosis of the jaw (MRONJ) and to elucidate factors affecting recurrence in surgical treatment. Materials and Methods: A total of 51 patients who were diagnosed with MRONJ were analyzed according to demographic and clinical features and treatment results through a retrospective chart review from 2013 to 2017 in the Department of Oral and Maxillofacial Surgery, Korea University Anam Hospital, Seoul in Korea. Results: Alendronate composed the majority of medication doses (55.6%), followed by ibandronate (20.0%), risedronate (15.6%), and zoledronate (6.7%). Forty patients (88.9%) were given oral medication, and five patients (11.1%) were intravenously treated, and the mean duration of medication use was $61.1{\pm}42.9$ months. A total of 10 patients (22.2%) had a drug holiday before MRONJ-induced dental treatment lasting an average of $6.8{\pm}7.0$ months. MRONJ occurred 2.7 times more in the mandible, with 41 cases (73.2%) occurring in the mandible and 15 cases (26.8%) occurring in the maxilla, and the prevalence of affected posterior parts (premolar-molar) was six times greater than that of the anterior parts (incisor-canine) (48 cases vs 8 cases, 85.7% vs 14.3%). The most common dental cause of MRONJ was tooth extraction (69.6%). Regarding recurrence, there was no statistical difference in recurrence rate according to either site or stage. However, recurrence occurred in 4 out of 34 cases (11.8%) in the primary closure group and 9 out of 20 cases (45.0%) in the secondary healing group, and there was a statistical difference with respect to closure technique. Conclusion: The identified risk factors in patients taking bone resorption inhibitors can aid dental clinicians in ensuring prevention and proper treatment of MRONJ.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권6호
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• pp.397-402
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• 2009

The purpose of this study is to investigate the effects of alendronate and pamidronate on proliferation and the alkaline phosphatase activity of human bone marrow derived mesenchymal stem cells and to relate the results with bisphosphonate related osteonecrosis of the jaw(BRONJ). With the consent of patients with no systemic disease and undergoing iliac bone graft, cancellous bone was collected to obtain human bone marrow derived mesenchymal stem cells through cell culture. 96 well plate were prepared with a concentration of $10^4$cell/ well. Alendronate and pamidronate were added to each well with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively. Then proliferation capacity of each well was evaluated with the cell counting kit. 24 well plates were prepared with a concentration of $10^5$cell/ml/well and with the bone supplement, alendronate and pamidronate were added with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively on each plate. The plates were cultured for either 24 or 72 hours. Then the cells were sonicated to measure the alkaline phosphatase activity and protein assay was done to standardize the data for analysis. As the concentration of alendronate or pamidronate added to the culture increased, the proliferation capacity of the cells decreased. However, no statistical significance was found between the group with $10^{-10}M$ of bisphophonate and the control group. Pamidronate was not capable of increasing the alkaline phosphatase activity in all trials. However, alkaline phosphatase activity increased with 24 hours of $10^{-8}M$ of alendronate treatment and with 48 hours of $10^{-10}M$ of alendronate treatment. Cell toxicity increased as the bisphosphonate concentration increased. This seems to be associated with the long half life of bisphosphonate, resulting in high concentration of bisphosphonate in the jaw and thus displaying delayed healing after surgical procedures. Alendronate has shown to increase the alkaline phophatase activity of human bone marrow derived mesenchymal stem cells. However, this data is insufficient to conclude that alendronate facilitates the differentiation of human bone marrow derived mesenchymal stem cells. Further studies on DNA level and animal studies are required to support these results.