• 대한치과교정학회지
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• 제29권1호
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• pp.95-106
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• 1999

백서에서 실험적 치아 이동시 bisphosphonate가 파골세포의 형성에 미치는 영향과 골 흡수 억제기전을 규명하고 독성유무를 알아보고자 하였다. 체중 260-350g의 웅성 백서 87마리를 정상군(장치비장착 + $0.9\%$ NaCl), 대조군(장치장착 + $0.9\%$ NaCl) 및 장치장착후 bisphosphonate 투여군(0.8 mg, 4 mg, 20 mg, 및 100 mg/kg) 으로 분류하였다. 상악 좌측 제1대구치를 근심으로 치아이동이 일어나도록 50-70g의 교정력을 가하고, 교정장치 장착후 1일, 3일 및 7일째에 혈청 acid phosphatase와 lactate dehydrogenase (LDH)의 활성도를 측정하고, 또한 제1 대구치를 포함한 상악골 일부에서 파골세포수 및 골흡수 정도를 조직학적으로 관찰하여 다음과 같은 성적을 얻었다. 1. Acid phosphatase 활성도는 장치후 1일째와 3일째에 대조군과 bisphosphonate 투여군에서 모두 정상군에 비해 2-3배 높았으나, 7일째에는 정상군과 유의한 차이를 보이지 않았다. 2. LDH활성도는 bisphosphonate 4 mg과 20 mg/kg 투여군에서 전 실험기간에 걸쳐 증가된 양상을 보였으나 0.8 mg과 100 mg/kg 투여군에서는 유의한 차이를 나타내지 않았다. 3. 골흡수는 장치후 1일째에 대조군과 bisphosphonate투여군에서 모두 관찰되지 않았으나, 3일 이후에 나타나 7일째까지 지속되었다. Bisphosphonate 4, 20 및 100 mg/kg군에서의 골흡수정도는 3일째에는 대조군에 비해 미약하였으나 7일째에는 대조군과 유사하게 나타났다. 4. 파골세포는 1일째에 대조군이나 bisphosphonate투여군 모두에서 거의 관찰할 수 없었다. 3일째에 대조군에서는 파골세포가 다량 출현하였으나 bisphosphonate 투여군에서는 약물의 용량이 증가함에 따라 감소하여 나타났다. 이상의 결과로 실험적 치아이동시 파골세포의 형성억제가 bisphosphonate에 의한 골흡수 억제기전이 아님을 알 수 있었고, bisphosphonate는 투여량이 증가에 따른 뚜렷한 세포독성은 관찰되지 않았으며, 골흡수 억제효과를 지속시키기 위해서는 약물이 반복적으로 투여되어야 할 필요가 있음이 시사되었다.

• 대한치과의사협회지
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• 제49권7호
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• pp.372-377
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• 2011

Bisphosphonates are widely used in the management of osteoporosis patients. Many reports and clinical studies have published a relationship between necrotic bone lesions localized to the jaw and the use of chronic bisphosphonate therapy. This osteonecrosis named bisphosphonate-related osteonecrosis of the jaw(BRONJ). This article described the mechanism, chemical structure, indication, risk factor of the bisphosphonate.

• 대한치과교정학회지
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• 제26권2호
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• pp.163-174
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• 1996

본 실험은 서로 다른 기전으로 골흡수를 억제한다고 추정되는 약제인 bisphosphonate와 indomethacin을 백서에 투여한 후 교정력을 이용한 치아이동시 약제가 골개조에 미치는 영향을 밝히고자 시행되었다. 동일한 조건에서 사육된 체중 260-300g의 웅성백서(Sprague-Dawley계)를 대조군, bisphosphonate 투여군 및 indomethacin 투여군으로 분류하고 각 군은 다시 장치를 장착한 실험측과 장치를 장착하지 않은 대조측으로 분류하였다. Bisphosphonate(6.3mg/kg,$2.52x10^{-2}mol/L$)와 indomethacin(9mg/kg, $2.52x10^{-2}mol/L$)은 교정장치 장착 6시간 전, 1시간 전 및 24시간 후에 복강내 주사하였으며, 교정력이 가해진 시점으로부터 72시간이 경과한 후 파골세포수를 측정하고 조직학적인 성상을 관찰하였다. 또한 혈액을 채취한 후 혈청 acid phosphatase 및 lactate dehydrogenase 양을 측정하여 다음과 같은 성적을 얻었다. 실험측의 파골세포수는 장치장착 1시간 전에 투여한 bisphosphonate군과 indomethacin군에서 가장 적게 나타났으며, 다른 시간의 약물 투여군은 대조군과 차이가 없었다. 대조측의 파골세포수는 실험측보다 현저히 적게 나타났으며, 대조군 및 약물투여군간에 차이가 없었다. 대조군과 6시간 전 및 24시간 후에 투여한 indomethacin군은 심한 골흡수 양상을 보인 반면, 1시간전 indomethacin군 및 모든 bisphosphonate군에서는 골흡수의 정도가 적었다. 파골세포의 주름변연과 투명대는 대조군 및 indomethacin군에서 가장 뚜렷하게 나타났으며, bisphosphonate 투여군에서는 일부 파골세포들이 무딘 세포돌기만을 내거나 골표면에 부착하지 않고 있는 경우가 많았다. Bisphosphonate와 indomethacin 투여군 모두에서 acid phosphatase 및 lactate dehydrogenase 값이 대조군보다 낮았으며, acid phosphatase 값은 bisphosphonate군이 indomethacin군보다 낮았으나 lactate dehydrogenase 값은 차이가 없었다. 이상의 결과로 bisphosphonate는 파골세포의 수 및 대사활동을 감소시키며 indomethacin은 파골세포의 수를 감소시킴을 알 수 있었다. 또한 두 약물을 비교하면 bisphosphonate는 indomethacin에 비해 골흡수 억제효과가 더 크며 투여시간에 따른 제약도 더 적은 것으로 사료된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권6호
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• pp.508-514
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• 2010

Bisphosphonates are used effectively for many medical conditions, such as multiple myeloma, Paget's disease, osteoporosis, etc. However, recently, osteonecrosis of the jaw was observed in patients receiving long-term bisphosphonate therapy, including oral administration. This osteonecrosis is refractory, and complete recovery is not guaranteed despite a standard treatment protocol being established by many associations related to oral and maxillofacial surgery. The treatment outcome of oral bisphosphonate-related osteonecrosis of jaw (BRONJ) is reported with a review of the relevant literature.

• 대한치과의사협회지
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• 제49권7호
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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.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제36권2호
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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.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제41권
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• pp.11.1-11.6
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• 2019

Background: Botulinum toxin injection on the masticatory muscle induces the osteopenic condition on the ipsilateral condyle. Bisphosphonate suppresses bone resorption and is used to treat osteopenic or osteoporotic condition. This study aimed to evaluate the effect of bisphosphonate administration on prevention of condylar resorption and botulinum toxin A-induced disuse osteopenia in rats. Results: The volume of the condyle and bone volume/tissue volume (BV/TV, %) showed a strong tendency towards statistical significance (p = 0.052 and 0.058). Trabecular thickness (Tb.Th, mm) and trabecular number (Tb.N, 1/mm) were significantly smaller in the Botox group than in the other groups (p < 0.05). The volume of the condyle and BV/TV in the bisphosphonate 100 and bisphosphonate 200 groups showed similar values when compared with the control group. Conclusion: Bisphosphonate administration after botulinum toxin A injection in the masticatory muscles appears to prevent condyle resorption and botulinum toxin-induced disuse osteopenia in rats.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권5호
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• pp.353-360
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• 2009

Bisphosphonates are compounds widely used in the treatment of various metabolic and malignant bone disease. Recently, an association between bisphosphonate use and a rare dental condition termed 'osteonecrosis of the jaw(ONJ)' has been reported. Bisphosphonate-related osteonecrosis of the jaw(BRONJ) is rare, but serious, side effect of bisphosphonate therapy in affected patients. It is characterized by poor wound healing and spontaneous intra-oral soft tissue break down, which lead to exposure of necrotic maxillary and mandibular bone. We reviewed 11 patients of BRONJ visited Ajou University Hospital Dental clinic from May 2007 to November 2008. The management of the patients included cessation of bisphosphonate therapy and various surgical restorative procedures and conservative care there after. Aggressive debridement is contraindicated. A new complication of bisphosphonate therapy administration, osteonecrosis of jaws, seems to be developing. The improved results after cessation of the medication should make clinicians reconsider the merits of the rampant use of bisphosphonates, while further investigation is needed to completely elucidate this complication.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제48권4호
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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.

• The Journal of Advanced Prosthodontics
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• 제5권4호
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• pp.374-381
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• 2013

PURPOSE. The purpose of this study was to evaluate the effect of alendronates on bone remodeling around titanium implant in the maxilla of rats. MATERIALS AND METHODS. The maxillary first molars were extracted and customized-titanium implants were placed immediately in thirty male Sprague-Dawley rats. The rats were divided into experimental (bisphosphonate) group and control group. At 4 weeks after implantation, the rats in the bisphosphonate group were subcutaneously injected with alendronate three times a week for 6 weeks where as the rats in control group were injected with saline. The rats were sacrificed at 1, 2, 3, 4, or 6 weeks after starting of injection and maxillary bones were collected subsequently. Alveolar bone remodeling around the implants were evaluated by radiographic and histologic analysis. Microarray analysis and immunohistomorphologic analysis were also performed on one rat, sacrificed at 6 weeks after starting of injection, from each group. Statistical analysis was performed using repeated measures analysis of variance and independent t test at a significance level of 5%. RESULTS. There was no statistically significant difference in the bone area (%) around implant between the bisphosphonate group and the control group. However, the amount of empty lacuna was significantly increased in the bisphosphonate group, especially in the rats sacrificed at 4 weeks after starting of injection compared to that of the corresponding control group. The bisphosphonate group showed the same level of TRAP positive cell count, osteocalcin and angiopoietin 1 as the control group. CONCLUSION. Alendronate may not decrease the amount of osteoclast. However, the significantly increased amount of empty lacuna in the bisphosphonate group may explain the suppression of bone remodeling in the bisphosphonate group.