역학적 강도 분석을 이용한 저강도 초음파의 조사 부위의 골다공증 골절 방지 효과 평가

우대곤,김치훈,박지형,고창용,김한성,김진만,김상희,임도형,Woo, Dae-Gon,Kim, Chi-Hoon,Park, Ji-Hyung,Ko, Chang-Young,Kim, Han-Sung,Kim, Jin-Man,Kim, Sang-Hee,Lim, Do-Hyung 대한의용생체공학회 2009 의공학회지 Vol.30 No.2

Purpose: The aim of present study is to evaluate a possibility of clinical application for the effect of low intensity ultrasound stimulation (LIUS) in mechanical characteristics of bone on osteoporotic fractures prevention. Materials and Methods: Eight virgin ICR mice (14 weeks old, approximate weight 25g) were ovariectomized (OVX) to induce osteoporosis. The right hind limbs were then stimulated with LIDS (US Group), whereas left hind limbs were not stimulated (CON Group). Both hind limbs of all mice were scanned by in-vivo micro-CT to acquire two-dimensional (2D) images at 0 week before stimulation and 3 weeks and 6 weeks after stimulation. Three-dimensional (3D) finite element (FE) models generated by scanned 2D images were used to determine quantitatively the effect of LIUS on strength related to bone structure. Additionally, distributions of Hounsfield units and elastic moduli, which are related to the bone quality, for the bones in the US and CON groups were determined to analyze quantitatively a degree of improvement of bone qualities achieved by LIUS. Results: The result of FE analysis showed that the structural strength in US Group was significantly increased over time (p<0.05), while that in CON Group was statistically constant over time (p>0.05). High values of Hounsfield units obtained from voxels on micro-CT images and high values of elastic moduli converted from the Hounsfield units were dominantly appeared in US Group compared with those in CON Group. Conclusion: These finding indicated that LIUS would improve the mechanical characteristics of osteoporotic bone via the effects of bone structure (bone strength) and quality (Hounsfield unit and elastic modulus). Therefore, the LIUS may decrease effectively the risk of osteoporotic fracture in clinics.

척추 골다공화 분석을 위한 형태학및 기계학적 고찰

우대곤,박지형,김치훈,김한성,이법이 대한체질인류학회 2008 대한체질인류학회 학술대회 연제 초록 Vol.51 No.-

3 차원 미세 유한요소모델을 이용한 골다공증 해면골과 호르몬 치료 모델의 기계적 특성 분석

우대곤(D. G. Woo),김한성(H. S. Kim),유용석(Y. S. You) 한국정밀공학회 2004 한국정밀공학회 학술발표대회 논문집 Vol.2004 No.10월

Several workers reported the relationship between osteoporosis and age-related reductions in the BV/TV (bone volume fraction) of vertebral trabecular bones. However, there were few micro finite element (micro-FE) models to account for the treatments of the osteoporotic trabecular bone. In the present study, micro-FE models of osteoporotic and hormone-treated bone models were constructed to analyze the effect of specimen location and boundary condition on mechanical characteristics of hormone treatment model for osteoporotic trabecular bone. Top and bottom sections of specimens were also investigated individually to study the effect of specimen location. Hormone-treated models were allowed to have the same relative BV/TV (13.4%) as that used in models of previous researchers. The present study reported the elastic and plastic characteristics of the osteoporosis and hormone-treated bone models. In the present study, in-situ boundary condition was applied to the simulated compression tests for in-vivo condition of vertebral trabecular bone. The present study indicated that the hormone therapy was likely to improve the mechanical characteristics of osteoporotic bones and the mechanical characteristics of vertebral trabecular bone specimen were dependent on the captured location and boundary condition.

시뮬레이터를 이용한 척추 추간판 변성의 실험적 유도

우대곤(D. G. Woo),김치훈(C. H. Kim),박지형(J. H. Park),김지현(C. H. Kim),김한성(H. S. Kim),임도형(D. Lim) 한국정밀공학회 2009 한국정밀공학회 학술발표대회 논문집 Vol.2009 No.6월

다공탄성체 척추운동분절 유한요소 모델을 이용한 추간판의 퇴화과정 분석

우대곤(D. G. Woo),김영은(Y. E. Kim) 한국정밀공학회 2005 한국정밀공학회 학술발표대회 논문집 Vol.2005 No.10월

To investigate the degeneration process in the intervertebral disc, a three dimensional (3D) poroelastic finite-element (FE) model was developed. Disc was modeled as two different regions, such as annulus modeled with fiber reinforced 20 node poroelastic ground matrix and nucleus having large porosity. Excess Von Mises stress in the disc element assumed to be a possible source of degeneration under compressive loading condition. Recursive calculation was continued until the desired convergence was attained by changing the permeability and porosity of those elements, which could be predicted from the previous iteration. The degenerated disc model showed that relatively small compressive stresses were generated in the nucleus elements compared to normal disc. Its distribution along the sagittal plane was matched well with a previously reported experimental result. Contrasts to this result, pore pressures in the nucleus were higher than those in the normal disc. Total stress indicated similar values for two different models. This new approach using poroelastic modeling could provide the explanation of the interaction between fluid and solid matrix in the disc during the degeneration process.

Micro -computed tomography를 이용한 골다공증의새로운 형태학적 연구기법

고창용,우대곤,김한성,이법이 대한체질인류학회 2005 대한체질인류학회지 Vol.18 No.4

Osteoporosis is a major health-care problem for aging communities. And postmenopausal osteoporosis is a common disorder characterized by an increase in bone resorption relative to bone formation, generally in conjunction with an increased rate of bone turnover.Twenty female rats were used as rat model of osteoporosis. They randomly were divided into two groups:a normal control group, and calcium-free diet groups treated with bilateral ovariectomy. The animals were sacrified at 12 weeks after treatment. In the rats with osteoporosis, there was significant thining and loss of trabeculae, accompanied by a disconnection of trabeculae. And acid mucopolysaccharides were decreased in osteoporotic animals. In order to setup conditions of invivo micro-CT, proper anesthetic is ketamine (50 mg/kg)/xylazine (6 mg/kg). And proper breathing rate of experimental animals is 1.3~1.6/sec. Our finding suggest that bilateral ovariectomy and calcium-free diet induce decrease in thickeness of trabecular bone and decrease in acid mucopolysaccharide, therefore cause weakness of bone. And micro-CT imaging system is useful to evaluate trabecular bone. Anesthetic time, anesthetics and respiration rate also signify much in micro-CT imaging system. 골다공증모델동물의 뼈잔기둥의 조직변화 및 골다공증모델연구에서 생체 내 미세 단층 촬영시스템(SKYSCAN1076, Skyscan, Belgium)을 적용하기 적합한 실험조건을 알아보고자 본시험을 수행하였다.암컷 흰쥐에게 난소적출과 저칼슘식이요법 (calcium free diet)을 시행하여 골다공증을 유발하였다. 골다공증의 유발된 흰쥐를 관류고정한후 허리뼈를 적출하여 탈회과정을 거친후 조직표본을 제작하여 골다공증모델동물의 뼈잔기둥에 대한 조직학적변화를 관찰하였다. 또한 흰쥐의 넷째 허리뼈를 35 µm의 해상도로 미세단층촬영을 시행하였다.골다공증 유발후 12주후에 척추뼈를 적출한후, 조직소견은 척추뼈의 뼈잔기둥의 두께가 감소하였고 일부 뼈잔기둥에서는 단락이 관찰되었으며, 뼈잔기둥내 산성점액질이 감소된 양상이 관찰되었다. 생체 내 미세 단층 촬영시스템의 평균 촬영시간은 20분정도 소요되었으며, pentobarbital, chloral hydrate, ketamine/xylazine 등의 마취제를 사용한 결과 ketamine/xylazine을 사용시 촬영에 가장 적절한 호흡주기(1.3~1.6/sec)를 유지하였으며, 마취제의 농도는 ketamine은 체중 kg당 50 mg, xylazine은 체중 kg당 6mg이 적정한 농도였다.이상의 결과를 종합한바, 난소적출과 저칼슘식이요법은 뼈잔기둥의 두께감소 및 산성점액질의 감소를 초래하여 뼈를 약화시키는 것으로 사료되며, 또한 고화질 생체내 미세단층촬영시스템을 이용하여 골다공증모델동물연구하는데 있어, 마취시간, 마취제 및 호흡주기가 중요한 요인이 되리라 사료된다.

IN-VIVO MICRO-CT와 미세 유한요소법를 이용한 쥐의 골다공증 해면골과 피질골의 구조적 특성 추적관찰 및 기계적 특성 분석

고창용,우대곤,김한성,이법이,탁계래 한국정밀공학회 2005 한국정밀공학회 학술발표대회 논문집 Vol.2005 No.5월

호르몬 결핍이 척추체에 미치는 영향 평가 : 골의 구조학적 및 질적 요소 분석

김치훈(Chi Hoon Kim),우대곤(Dae Gon Woo),박지형(Ji Hyung Park),이법이(Beob Yi Lee),김지현(Chi Hyun Kim),김한성(Han Sung Kim) Korean Society for Precision Engineering 2010 한국정밀공학회지 Vol.27 No.5

원자힘 현미경을 이용한 성장기 흰쥐의 호르몬 결핍이 무릎 연골세포에 미치는 영향 분석

김치훈 ( Chi Hoon Kim ),우대곤 ( Dae Gon Woo ),박지형 ( Ji Hyung Park ),전옥희 ( Ok Hee Jeon ),이승학 ( Seung Hak Lee ),김지현 ( Chi Hyun Kim ),윤대성 ( Dae Sung Yoon ),김한성 ( Han Sung Kim ) 한국조직공학과 재생의학회 2010 조직공학과 재생의학 Vol.7 No.4

The present study was designed to evaluate the correlation between osteoporosis and osteoarthritis, based on micro-computed tomography (Micro-CT) and atomic force microscopy (AFM). To induce osteoporosis, virgin Sprague-Dawley rats (6 weeks old) were ovariectomized (OVX). All rats were randomly divided in two groups (normal group: 9, OVX group: 6). Knee joint on each rat was scanned by Micro-CT with 18-μm resolution at 0, 4 and 8 weeks. Morphological characteristics were calculated by Micro-CT image analyzer. Knee joint chondrocytes were isolated and immobilized to investigate morphological and mechanical characteristics on AFM measurements. In the OVX group, morphological characteristics significantly changed at all the femur over time(p<0.05). Comparing OVX group to normal group at 8 weeks, morphological characteristics and stiffness of chondrocytes measured by AFM significantly increased in normal group more than OVX group(p<0.05). The results showed that osteoporosis can cause osteoarthritis. The finding of the present study indicated that AFM can analyze the origin of osteoarthritis. In addition, this study is valuable attempt to find the correlation between osteoporosis and osteoarthritis.

성장기 저칼슘 섭취가 척추 골다공증 발생과 척추사이원반 변성에 미치는 영향 평가

박지형(Ji-Hyung Park),우대곤(Dae-Gon Woo),김치훈(Chi-Hoon Kim),이법이(Beob-Yi Lee),김지현(Chi-Hyun Kim),김한성(Han-Sung Kim) 대한체질인류학회 2009 해부·생물인류학 (Anat Biol Anthropol) Vol.22 No.3

본 연구는 성장기 때 저칼슘 섭취가 최대뼈질량을 감소시키고 뼈엉성증의 요인이 된다고 가정하고 칼슘제거사료를 공급하여 실험을 구성하였다. 변성된 척추사이원반은 해면뼈에 압력분포를 줄여주고 겉질뼈와 척추뒤돌기(가시돌기)의 압력분포를 증가시키며 해면뼈 면적을 줄여주어 골다공증을 유발할 수 있다는 다수의 연구가 발표되었지만, 골다공증이 유발된 척추가 척추사이원반 변성에 영향을 준다는 연구는 적고 골다공증이 유발된 척추에 인접한 정상 척추사이원반은 변성될 가능성이 있다는 가정을 확인하고자 하였다. 골다공증이 유발된 척추를 확인하기 위하여 살아있는 암컷 흰쥐의 허리뼈 전체(L1~L6)를 생체 내 미세단층촬영 시스템으로 촬영하고 유한요소 모델생성 및 가상 압축실험을 통하여 허리뼈의 형태학적 및 기계학적인 특성을 평가하였다. 골다공증으로 인한 척추의 골량감소와 미세구조의 변형이 척추사이원반에 어떤 영향을 미치는지를 확인하기 위해 조직학적 방법으로 관찰하였다. 통계처리는 일변량 ANOVA검정, Tukey’B검정, 대응표본 T검정을 수행하였다(p<0.05). 정상군의 해면뼈는 전체적으로 골량이 증가하였으나 칼슘제거군의 해면뼈는 골량이 감소하였다. 0주, 4주, 8주의 칼슘제거군에서 L3, L4, L5의 구조적 요소가 L1, L2, L6보다 모두 낮게 평가되었고, L3, L4, L5에서 해면뼈의 강도가 다른 부분에 비해 상대적으로 약한 구조임을 관찰할 수 있었다. 0주에서는 건강한 척추사이원반이 관찰되었다. 4주와 8주에서는 높이가 상대적으로 줄어들고 형태가 변하여 함몰된 모습을 관찰할 수 있다. 본 연구에서는 성장기에 칼슘을 섭취하지 못하면 뼈손실이 크게 발생됨을 확인할 수 있었다. 기존연구에서 더 나아가 첫째 허리뼈에서 여섯째 허리뼈까지(L1~L6) 골다공화에 따른 해면뼈의 구조적 및 기계적 특성 변화와 집중 하중을 받는 척추사이원반을 관찰하여 상호 연관성을 검토하였다. 골다공증은 뼈대계통 전체적으로 발생하나 허리뼈의 중심 부위인 L3, L4, L5가 외곽 부위인 L1, L2, L6에 비해서 약 1.8배 정도(중심부위: 122±101, 외곽부위: 224±118) 기계적 강도가 더 약하므로 L3, L4, L5의 해면뼈에서 골다공증이 가장 먼저 유발됨을 관찰하였고, 해면뼈의 뼈손실과 미세구조 변화에 따른 척추사이원반의 변성이 발생됨을 확인하였다. The aim of the present study is to analyze the generation of osteoporotic vertebral bone induced by malnutrition during growth period and analyze its effects for disc degeneration, based on biomechanical and histomorphometrical study. Mechanical and histomorphological characteristics of lumbar vertebral bones and discs of rats with calcium free diet (CFD) were detected and tracked by using high resolution in-vivo micro-computed tomography (in-vivo micro-CT), finite element (FE) and histological analysis. Twenty female Sprague-Dawley rats (6 weeks old, approximate weight 170g) were randomly divided into two groups (CFD group: 10, NOR group: 10). The CFD group was maintained on a refined calcium-controlled semisynthetic diet without added calcium, to induce osteoporosis. All lumbars (L1~L6) were scanned by using in vivo micro-CT with 35 μm resolution at 0, 4, 8 weeks to track the effects of CFD on the generation of osteoporosis. The results of morphological characteristics showed that BV/TV, Tb.Th, Tb.N in CFD group were significantly decreased over time (p<0.05), while those in NOR group were statistically increased over time (p<0.05) in the most lumbars (L1~L6). We also investigated the contrary tendency in Tb.Sp and SMI, compared to the above results in each group. In the simulated compression test using FE models, the structural effective modulus of CFD group significantly decreased (p<0.05), whereas that of NOR group was statistically increased, depending on the measuring time (p<0.05). The present study observed remarkable histological changes of nucleus pulposus and annulus fibrous by water loss in CFD group, compared with NOR group. These findings indicated that calcium insufficiency was the main factor in the generation of osteoporosis and it induced lumbar vertebral disc degeneration. This study is a valuable experiment to firstly evaluate osteoporotic vertebral bone and disc degeneration induced by malnutrition during growth period from a biomechanical and histomorphometrical point of view.