• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권1호
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• pp.10-18
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• 2011

Purpose: The purpose of this study is to find out the effects of bisphosphonates (BPs) on the proliferation and the alkaline phosphatase (ALP) activity of human bone marrow derived mesenchymal stem cells (hMSCs), and thus state its correlation with bisphosphonate related osteonecrosis of the jaw (BRONJ). Methods: hMSCs was obtained by collecting and culturing cancellous bone fragments from a patient undergoing iliac bone graft. Alendronate (Aln) and Pamidronate (Pam), Ibandronate (Ibn) were added to the culture media in the concentration from $10^{-3}$ M to $10^{-11}$ M and cell toxicity, viability were measured. For ALP activity evaluation, Aln and Pam were added to the culture media in the concentration from $5{\times}10^{-7}$ M to $1{\times}10^{-8}$ M and were cultured for 1 week, 2 weeks and 3 weeks. ALP activity data were standardized using protein assay. Control groups were prepared for each examination. Results: Aln, Pam and Ibn all failed to increase the proliferation of hMSCs. With 1 week, 2 weeks of $5{\times}10^{-8}$M of Aln treatment, the ALP activity increased. Pam treatment increased the ALP activity with 2 weeks of $5{\times}10^{-8}$ M and$1{\times}10^{-8}$M. Also Ibn treatment increased the ALP activity with 2 weeks of $5{\times}10^{-8}$ M and $1{\times}10^{-8}$ M. Conclusion: It is considered that BPs are not capable of improving the proliferation of hMSCs. Also, after a transient increase in the ALP activity with the lower concentration of BPs, the activity decreased again. Therefore, in patients on long-term medication of BPs, the proliferation and osteoblast differentiation of hMSCs are restrained, and thus delayed wound healing and increase in BRONJ complications may occur.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1357-1362
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• 2014

Background: Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer (BC) prevention. It may also be related to prognosis after diagnosis and treatment. The aim of our study was to determine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levels in patients with BC and to evaluate its correlations with life-style and treatments. Materials and Methods: This study included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlation between serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usage of bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments and radiotherapy were investigated. The distribution of serum 25-OHD levels was categorized as deficient (<10ng/ml), insufficient (10-24 ng/ml), and sufficient (25-80 ng/ml). Results: The median age of the patients was 51 years (range: 27-79 years) and 70% of them had deficient/insufficient 25-OHD levels. On univariate analysis, vitamin D deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at the baseline, high BMI (${\geq}25$), no bisphosphonate usage, and a conservative dressing style. On multivariate analysis, none or low dose vitamin D supplementation, and decreased sun-exposure due to a conservative dressing style were found as independent factors increasing risk of vitamin D deficiency/insufficiency 28.7 (p=0.002) and 13.4 (p=0.003) fold, respectively. Conclusions: The prevalence of serum 25-OHD deficiency/insufficiency is high in our BC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservative dressing style, as part of regular preventive care, and they should take supplemental vitamin D.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제39권1호
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• pp.9-13
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• 2013

Objectives: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. Materials and Methods: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. Results: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was $70.0{\pm}10.1$ years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. Conclusion: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권6호
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• pp.470-476
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• 2011

Introduction: The incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) has increased gradually in patients who have undergone surgical treatment for osteomyelitis. In this study, a retrospective analysis of BRONJ patients was carried out using the data of osteomyelitis patients treated surgically. Materials and Methods: Osteomyelitis patients, who underwent curettage, sequestrectomy, saucerization or decortications, and partial mandibulectomy at Seoul National University Dental Hospital from 2004 to 2010 were enrolled in this study. The patients were classified and categorized into two groups based on the surgical records and progress notes. One group comprised of patients with osteomyelitis and osteoporosis, and the other group included patients with osteomyelitis only. The epidemiological data of the BRONJ patients was analyzed to identify any trend in the incidence of BRONJ in osteomyelitis patients. Results: Among 200 patients who underwent surgical intervention for osteomyelitis, 64 (32.0%) were identified as having osteoporosis as the underlying disease. In these 64 patients, more than 81.3% had been prescribed bisphosphonates. Females were far more affected by BRONJ than males. The incidence of BRONJ also increased with age. The posterior part of the mandible was affected more frequently by BRONJ. Conclusion: Although the availability of potent antibiotics and increased oral hygiene care can reduce the overall incidence of osteomyelitis, BRONJ can increase the total incidence. To prevent BRONJ, it is recommended that an oral examination be performed before prescribing bisphosphonates. Moreover, the patients should be educated about the potential risks of dental procedures that might be causal factors for BRONJ. Furthermore, patient swho take bisphosphonates for the treatment of osteoporosis should undergo periodic follow up oral examinations to prevent BRONJ.

• Journal of Yeungnam Medical Science
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• 제25권1호
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• pp.19-30
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• 2008

골다공증은 골밀도와 골의 질로 구성되는 골의 강도가 손상됨으로 골절의 위험이 높아지는 골격질환이며, 최근 유병율이 점차 증가하고 있는 추세이다. 임상적으로 무증상인 경우가 많으며 방사선학적 검사인 단순 방사선 검사, 골 스캔, CT, MRI 등이 골밀도 및 골절의 진단에 유용하다. 골밀도의 정량적 검사로는 이중에너지 방사선 흡수법, 정량적 전산화 단층촬영이 사용되고 있다. 골다공증의 진단은 WHO 기준에 따라 T-score가 -2.5 이하일 경우 진단할 수 있다. 그 외에 생화학적 골표지자들도 진단에 도움이 된다. 골다공증 치료제는 골흡수억제제와 골형성자극제(formation stimulator)로 나눌 수 있는데 골흡수억제제로는 칼슘, 에스트로겐, 칼시토닌, 비스포스포네이트(bisphosphonate), 비타민 D 등이 있으며 골량을 증가시키는 골형성자극제로는 현재 부갑상선 호르몬이 유일하며 최근 strontium ranelate가 추가되었다. 일일 1200 mg의 칼슘과 800 IU 의 비타민 D 섭취가 권장되고 있으며, 폐경기 여성에서 에스트로겐이 효과가 입증되었고 골다공증으로 인한 통증에는 칼시토닌이 효과가 있다. 비스포스포네이트는 폐경 후 골다공증의 치료, 예방 및 스테로이드에 의한 골다공증 치료에 대해 FDA의 승인을 받았다. 폐경 후 골다공증의 치료, 예방에 사용되는 SERM은 골의 질을 향상시킴으로써 골절을 예방한다고 알려져 있다. 골형성자극제인 부갑상선 호르몬이 골절의 위험을 감소시킨다고 보고된 바 있으며, strontium은 최근에 개발된 약제로 3상 연구에서 골절 위험율 감소효과를 보였으나 더 많은 연구가 필요할 것으로 생각된다.

• Childhood Kidney Diseases
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• 제18권2호
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• pp.92-97
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• 2014

목적: 비스포스포네이트는 스테로이드 유발성 골다공증을 앓고 있는 환자의 치료에 널리 사용되어 왔다. 비스포스포네이트의 사용이 증가되면서 성장 중인 뼈에서 보이는 방사선학적 이상 소견에 대한 몇몇 보고가 있었다. 그래서 소아 환자에서 비스포스포네이트를 사용하는 것에 대해서는 논란의 여지가 있다. 이번 연구는 신병증을 가진 소아 환자에서 파미드로네이트 치료를 했을 때 발생한 방사선학적 이상 소견, 특히 골간단 경화성 선을 장기간 추적 관찰한 결과를 알기 위한 것이다. 방법: 경구로 칼슘제와 파미드로네이트(용량: 매일 100 mg)를 복용한 24명의 신병증 환아(평균 복용 기간: 9개월)를 후향적으로 연구하였다. 모든 대상 환아는 신병증에 대한 치료로 장기간 스테로이드 치료를 받았기 때문에 스테로이드 유발성 골다공증을 앓고 있었다. 파미드로네이트 치료 전에 장골의 방사선 사진을 촬영하였으며 수년간 추적 관찰 하였다. 뼈의 성장 속도는 검사를 시행한 시간 간격에 따라 방사선 사진 상에서 경화성 선이 이동한 거리를 측정하여 계산하였다. 결과: 평균 추적 관찰 기간은 138개월이었다. 장골의 방사선 사진 상, 모든 환자에서 골간단의 끝부분에서 뚜렷한 경화성 선이 관찰 되었으며 이 경화성 선은 성장판에서 골간쪽으로 점점 이동하였다 경화성 선의 평균 이동 속도는 6.21 mm/년이었다. 24명 중 12명의 환자에서는 경화성선이 완전히 사라졌다. 그리고 평균 키의 성장 속도는 7.33 cm/년이었다. 결론: 이번 연구에서 장기간 동안 추적 관찰한 결과 파미드로네이트 치료와 연관된 골간단부의 경화성 선은 뼈 성장에 영향을 주지 않았으며 점점 없어지는 경향을 보였다. 그러므로 신병증을 가진 소아 환자에서 스테로이드 유발성 골다공증을 비스포스포네이트로 치료하는 것은 안전한 것으로 생각된다. 그러나 좀 더 많은 수의 환자를 대상으로 하는 추가적인 연구가 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.553-558
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• 2012

Purpose: This article reviews a few of the commonly used types of vascularized osseous free flaps in maxillofacial reconstruction, which still represents the gold standard of restoration. We also discuss the developing concepts in maxillofacial reconstruction. Recent findings: Most of the literature reconfirms the established patterns of reconstruction with the aid of vascularized osseous free flaps. This method of free-tissue transfer is also feasible in cases of osteoradionecrosis or bisphosphonate-related osteonecrosis of the jaw. These flaps are also suitable for prosthetic restoration using osseointegrated dental implants. Summary: Vascularized osseous free flaps still remain the standard of care. Improvements upon the free-tissue transfer method employing vascularized osseous free flaps, such as distraction osteogenesis, tissue engineering, and imaging techniques, currently require further development, but these technologies could lead to improved outcomes of maxillofacial reconstruction in the near future.

• Journal of Korean Neurosurgical Society
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• 제50권2호
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• pp.134-138
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• 2011

The authors report a case of epidural and extraforaminal calcification caused by repetitive triamcinolone acetonide injections. A 66-year-old woman was admitted presenting with lower extremity weakness and radiating pain in her left leg. Ten months before admission, the patient was diagnosed as having an L4-5 spinal stenosis and underwent anterior lumbar interbody fusion followed by posterior fixation. Her symptoms had been sustained and she did not respond to transforaminal steroid injections. Repetitive injections (10 times) had been performed on the L4-5 level for six months. She had been taking bisphosphonate as an antiresorptive agent for ten months after surgery. Calcification in the ventral epidural and extraforaminal space was detected. The gritty particles were removed during decompressive surgery and these were proven to be a dystrophic calcification. The patient recovered from weakness and radiating leg pain. Repetitive triamcinolone acetonide injections after discectomy may be the cause of dystrophic calcification not only in the degenerated residual disc, but also in the posterior longitudinal ligament. Possible mechanisms may include the toxicity of preservatives and the insolubility of triamcinolone acetonide. We should consider that repetitive triamcinolone injections in the postdisectomy state may cause intraspinal ossification and calcification.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제42권6호
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• pp.365-369
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• 2016

Objectives: To determine the prevalence and oral characteristics of cancer patients treated with bisphosphonates in the oncology and maxillofacial prosthesis departments of the General Hospital of Mexico between 2011 and 2013. Materials and Methods: This cross-sectional study included patients who received prior treatment with bisphosphonates; an intraoral examination was performed by 2 standardized examiners. Results: The prevalence of bisphosphonate-related necrosis in 75 patients was 2.6%; the most common malignancy was breast cancer (84.0%), followed by prostate cancer (16.0%). Exostosis was present in 9.3% of patients and the mean Decayed, Missing, Filled Teeth index was 4.64; 44.0% of the study group had a Community Periodontal Index value between 2 and 2.9 (mean, 0.60). Conclusion: A detailed intraoral assessment must be performed before initiating treatment with bisphosphonates to identify risk factors for osteonecrosis.

• 대한치과의사협회지
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• 제54권4호
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• pp.274-283
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• 2016

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.