약제관련 악골괴사증 환자의 괴사골편 및 제거된 임플란트에 대한 전자현미경 분석

학위논문(석사) -- 서울대학교대학원 : 치과대학 치의과학과, 2022. 8. 김성민.Introduction Bisphosphonate (BP), a commonly used medication for various bone diseases including osteoporosis and bone malignancy, has been known to have severe complications. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of these complications, and many clinicians and researchers have published its cause and clinical or histological findings, until recently. Failure of dental implants has been also found in a patient with BRONJ. We analyzed the necrotic bone tissues and the surface of the failed implants removed from the jaw in patients treated with BP for various reasons by using an electron microscope. Materials and methods A total of 5 necrotic bone tissues and 3 implant surfaces removed from 5 patients with BRONJ at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, were analyzed by clinical, histological, elemental, and ultrastructural studies such as scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). Results Chronic inflammatory cells with collagen and fibrous tissue and a bone sequestrum were shown at 5.0 ×, 10.0 ×, 20.0 ×, and 40.0 × magnified histologic sections in the bone and fibrotic scar tissues removed due to osteonecrosis from a patient with BRONJ. Hardened bone tissues with microcracked bony resorbed lacunae were observed in the SEM findings, which were considered as the initial processes leading to osteonecrosis of the jaw. Not as findings of immune cells such as dendritic cells in the failed implant surface in the previous published comparative data, these immune cells were not identified in the BRONJ-related peri-implantitis tissues in the TEM investigations. Furthermore, EDS analysis revealed that, in addition to the main titanium element, gold, carbon, oxygen, calcium, phosphorus, and silicon elements were found. Sulfur was also found, which was considered to be one of the complicated causes of implant failure in patients with BRONJ. Conclusion Hardened bone tissues with microcracked bony resorbed lacunae were observed in the SEM findings, which were considered as the initial processes leading to osteonecrosis of the jaw. Immune cells such as dendritic cells in the failed implant surface in the BRONJ-related peri-implantitis tissues were not identified in the TEM investigations. EDS analysis showed in addition to the main titanium element, gold, carbon, oxygen, calcium, phosphorus, and silicon elements were found. And it was also revealed that sulfur was found, which was considered to be one of the complicated causes of implant failure in patients with BRONJ.연구의 배경 및 목적 비스포스포네이트는 골다공증 등 다양한 골질환에 주로 사용되는 약물로 이를 투여받은 환자 중 발생하는 악골의 골괴사가 가장 심각한 합병증으로 알려져 있다. 본 논문은 다양한 이유로 비스포스포네이트 등의 약제를 투여받은 환자에서 발생한 악골의 괴사에서 제거된 괴사골 조직 및 실패한 임플란트의 표면을 전자현미경을 이용하여 분석해 보았다. 연구방법 서울대학교 치과대학병원 구강악안면외과에서 BRONJ 로 진단된 환자 중 5명에서 제거된 5 괴사골 조직과 3 임플란트 표면을 임상적, 조직학적, 원소분석, 주사전자현미경 및 투과전자현미경으로 조사하였다. 연구결과 비스포스포네이트 치료를 받는 환자에게서 발생한 골괴사로 인해 제거된 골조직 및 섬유성 조직은 다양한 광학현미경 배율에서 만성 염증 및 콜라겐 조직으로 구성되어 있었고 그 내부에 일부 부골이 관찰되었다. 주사전자현미경분석에서는 경화된 골조직에서 미세균열(microcrack) 및 골흡수소강 (bone resorption lacunae)이 관찰되었고 이는 기존에 알려진 대로 비스포스포네이트 투여시 발생하는 골 내 미세균열이 악골 골괴사로 이어지는데 중요한 첫 번째 과정이라고 알려진 내용과 동일한 소견임을 확인할 수 있었다. 투과전자현미경분석에서는 비교할만한 이전 연구들에서 실패한 임플란트 표면에서 수지상세포 와 같은 면역세포가 관찰된다고 하였으나 BRONJ 와 연관된 임플란트 주위염 조직에서는 이런 면역세포들이 관찰되지는 않았다. 또한 에너지 분선형 X선 분광법 분석에서는 임플란트의 주성분인 티타늄(Ti) 뿐만 아니라 금(Au), 탄소(C), 산소 (O) 이외에도 칼슘(Ca) 인(P), 실리콘(Si) 등이 관찰되었다. 또한 황 (S(sulfur)) 가 나온 것을 확인할 수 있었고 이는 BRONJ 환자에서 임플란트 실패의 복합적 원인 중 하나가 될 수 있을 것으로 사료된다. 결론 약제 관련 골괴사 환자에서 제거된 괴사골 및 임플란트 표면을 전자현미경적 기법으로 연구하여, 미세균열의 골흡수 열공이 있는 조직을 관찰하였는데, 이는 악골의 골괴사로 이어지는 초기 과정으로 판단된다. 괴사골 및 임플란트 주위염 조직에서 실패한 임플란트 표면의 수지상 세포와 같은 면역 세포는 관찰되지 않았으며, 원소분석에서는 티타늄 원소 외에 금, 탄소, 산소, 칼슘, 인, 규소 원소도 관찰되었다.I. Introduction 01 II. Materials and methods 03 II.1 Patients data 03 II.2 Specimen processes for histological and TEM analysis 04 II.3 Specimen processes for SEM-EDS analysis . 04 III. Results 06 III.1 Analyses of patients data 06 III.2 Histological and TEM analysis 13 III.3 SEM-EDS analysis 14 IV. Discussion 17 V. Conclusion 24 References 25 Figures and Figure Legends 31 Abstract in Korean 48 Acknowledgement 51석

Effects of managerial autonomy on performance in public enterprises : an empirical analysis

학위논문 (석사)-- 서울대학교 대학원 : 행정학과(행정학전공), 2011.2. 김준기.Maste

A Clinical Study on The Care of Oral Complications in The Admission Patients With Major Malignant Tumors

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