01-10 노성만(국)

EDITORIAL http://dx.doi.org/10.5371/hp.2012.24.4.265 Print ISSN 2287-3260 Online ISSN 2287-3279 Animal Experiment of Legg-Calve-Perthes Disease in Piglets, Puppies and Growing Rabbits Sung-Man Rowe, MD, PhD Department of Orthopedic Surgery, Chonnam National University Hwasun Geriatric Hospital, Jeonnam, Korea Legg-Calve-Perthes 병의동물실험 - 새끼돼지, 강아지, 어린토끼를중심으로 노성만전남대학교화순노인전문병원정형외과 Legg-Calve-Perthes Disease (LCPD) 는 1909-1910 년최초로보고된이래 100 년이라는긴세월이흘렀지만, 아직도소아고관절질환중가장미개척분야이며특히병의원인, 병의자연경과, 치료방법등의분야에서학자들간에서로다른의견을보이고있다. LCPD 가임상적으로관심의대상이되는것은환자들의상당수에서골두의변형이관찰되며이러한골두변형은속발성고관절염을초래하고나아가관절치환술의대상이되기때문이다. LCPD 의치료에있어서무엇보다중요한것은이러한골두변형의예방이다. 그러나많은학자들의노력에도불구하고발병의원인으로부터치료방법에이르기까지어느 Submitted: November 7, 2012 1st revision: December 11, 2012 2nd revision: December 20, 2012 Final acceptance: December 21, 2012 Address reprint request to Sung-Man Rowe, MD, PhD Department of Orthopedic Surgery, Chonnam National University Hwasun Geriatric Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasungun, Jeonnam 519-809, Korea TEL: +82-61-379-7676 FAX: +82-61-379-7681 E-mail: smrowe@chonnam.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 것도시원하게밝혀진것이없는실정이다 1). 이처럼 LCPD 가미해결분야의질환으로남아있는데에는 LCPD 가가지고있는아래와같은몇가지특성때문이다. 첫째로, LCPD 는사망에이르는질병이아니어서연구에필요한골두표본을얻기가쉽지않다. 둘째로, LCPD 는의사가직접육안으로병든골두를관찰할수있는기회가드물다. 우리가때로수술적접근을하지만환부인골두로부터거리가있는대퇴골절골술또는무명골절골술이어서관절낭을열고골두를관찰할수없다. 셋째로, disease period 가매우길어서충분한추적조사가어렵다. LCPD 는주로 6-8 세에발병하여성장완료시까지골두의변화가이어지기때문에최소 10 년가까이추적조사를하여야하며속발성관절염의발생여부를확인하기위하여서는수십년의추적이필요하다. 넷째로, 대부분문헌들은자연경과에대한연구가드물고, 대조군과의연구도결여되어있다. 다섯째로, 많은치료법이소개되어있으나확립된견해가없고학자에따라선호도가있을뿐이다. 이처럼다양한결함들을부분적으로나마해결하기위하여자연스럽게동물실험이시도되었지만동물실험은아직은초보단계이며많은한계점이지적되고있다. 또한동물실험은모든동물에서가능한것이아니어서문헌조사에의하면새끼돼지 2-4), 강아지 5,6), 그리고어린토끼 7-12) 가보고되어있을뿐이다. 저자가 LCPD 에관심을갖기시작한것은 1975 년이었다. Copyright c 2012 by Korean Hip Society 265

1975 년부터정년퇴임하던 2004 년까지 30 여년동안 LCPD 에매달렸다. 자연스럽게환자가늘어나정년무렵에는등록된환자가 872 명 (968 관절 ) 에달하였고이들중수백명이최소 10 년이상 follow-up 되었다. 그러나오랜시간의노력에도불구하고 LCPD 의미해결분야가좁혀져간다고느낄수가없었다. 자연스럽게동물실험의필요성을깨닫게되었고문헌조사를통하여 LCPD 와유사한형태학적변형을보이는동물이어린성장기의토끼, 새끼돼지, 그리고체구가왜소한애완용강아지임을알게되었다. 저자는 LCPD 에있어서미해결분야의일부만이라도해결할수있기를기대하면서십수년에걸쳐이들 3 종의동물을대상으로동물실험 4,5,10,11) 을해왔으며그중일부를정리하여보고한다 (Fig. 1). The Piglet Model 4) 1. 실험목적 LCPD 에있어서대퇴골두의육안및방사선상의병리해부학적변화를확인하기위하여 piglet model 을사용하였다. 특히 LCPD 의 4 major deformity pattern 인 coxa plana, coxa magna, coxa vara, 그리고 subluxation 을중심으로관찰하였다. 2. 실험방법 출생후 4-5 주 ( 체중 : 7-9 kg) 된 30 마리의잡종돼지 (Yorkshire and Landrace) 를사용하였다. 모두에서좌측고관절에서수술을시행하고우측고관절은대조군으로사용하였다. No.2 ethibond suture 로대퇴경부를감아묶고 (epiphyseal artery 의차단위함 ) capital femoral epiphysis 의혈류차단을위하여 ligamentum teres 을절단하였다. 30 마리중 2 마리는수술후 2 주내에죽고다른두마리는술후골절발생으로실험에서제외하였다. 나머지 26 마리는각실험시기에 6-7 마리씩도살하였다. 실험군은초기군은 2 주와 4 주, 중기군은 12 주, 후기군은 20 주로하였다 (Table 1). 초기군은 LCPD 의 avascular 또는 early fragmentation stage 에비슷하도록하여실제 LCPD 환자의초기병변을기대하였으며, 중기군은 fragmentatioin 과 healing stage 를기대하였으며, 후기군은골성장완료후관찰되는잔여병변을관찰하고자기대하였다. 실험시기에도달하면양측대퇴골과골반골을적출하고계획된관찰과측정을시행하고 X- 선촬영을시행한후조직검사를위하여 10% formalin 용액에보관하였다. A B C Fig. 1. (A-C) Photographs of animal models of LCPD in piglets, puppies, and growing rabbits. Table 1. Piglet Groups according to Postoperative Periods Postoperative Stage of Human Number of Piglets Femoral Length (cm) Body Weight (kg) Period (Weeks) LCPD Simulated ; Mean (SD) ; Mean (SD) Early Period 2 Weeks Avascular or Early 6 10.2 (0.7) 015 (2.9) Fragmentation 4 Weeks 6 11.5 (0.3) 022 (3.3) Intermediate Period 12 Weeks Fragmentation or Healing 7 15.8 (3.1) 062 (17) Late Period 20 Weeks Skeletal Maturity 7 18.8 (4.3) 107 (21) 266 www.hipandpelvis.or.kr

Sung-Man Rowe: Animal Experiment of Legg-Calve-Perthes Disease in Piglets, Puppies and Growing Rabbits 3. 실험결과 epiphyseal height 의평균감소 (coxa plana) 는술후 2 주군은 1.5 mm, 4 주군은 4.1 mm, 12 주군은 5.0 mm 그리고 20 주군은 7.2 mm (rs=0.76, P=0.002) 였다. 대퇴골두직경의평균증가 (coxa magna) 는 4 주군은 4.1 mm, 12 주 군은 6.9 mm 그리고 20 주군은 6.8 mm 였다. Articulotrochanteric distance 의평균감소 (coxa vara) 는 2 주군과 4 주군에서는 mild 그리고 12 주군과 20 주군은 severe 였다. 대퇴골두의 subluxation 은 12 주와 20 주군에서만관찰되었다 (Fig. 2) (Table 2). A B C D Fig. 2. (A-D) Composite radiographic findings from extracted femurs from a piglets sacrificed at postoperative week 4 (A), 8 (B), 12 (C), and 16 (D) showing gradual increase of coxa plana, coxa magna, and greater trochanter overgrowths. Table 2. Macroscopical and Radiological Changes of the Femoral Head in 26 Piglets with Vascular Infarct Postoperative Weeks 2 4 12 20 Rs* P-value Experimental Animal Number 06 06 7 7 Coxa Plana Decrease in Epiphyseal Height ( 10%) Appearance Rate, Number 01 04 4 7 0.55 0.0.004 Mean Height, mm (95% CI) Operated Side 9.5 6.9 (3.1-11)..10 (8.3-12) 9.7 (8.7-11) Normal Side 11 11 (10-12). 15 (14-17) 17 (16-18) Mean Decreased (95% CI), mm 1.5 4.1 (0.4-7.8).5.0 (3.4-6.6).7.5 (5.6-9.4) 0.76 0.0.002 % 14 37 (4-71)0. 33 (23-44) 43 (34-53) 0.42 0.1. Flattering of Articular Surface Appearance Rate, Number 01 02 4 7 0.62 0.0.001 Extent, Number Localized 01 01 1 2 Generalized 00 01 3 5 Coxa Magna ( 10%) Appearance Rate, Number 00 01 5 6 0.70 <0.001 Mean Diameter, mm (95% CI) Operated Side - 29 40 (36-44) 43 (40-47) Normal Side - 25 33 (31-35) 37 (35-39) Mean Increase, mm (95% CI) - 4.1 6.9 (3.2-11).6.8 (3.9-9.6) 0.22 0.5. % - 16 21 (10-32) 18 (11-26) 0.02 0.9. Greater Trochanter Overgrowth ( 20%) Appearance Rate, Number 04 04 6 7 0.34 0.09 Grade, Number Mild 04 02 2 0 Severe 00 02 4 7 Lateral Subluxation Appearance Rate, Number 00 00 5 7 0.84 <0.001 * Rs: Spearman s Correlation Coefficient. www.hipandpelvis.or.kr 267

4. 실험결론 실험결과새끼돼지에서 LCPD 환자와유사한병리해부학적변화를관찰할수있었다. 특히새끼돼지의경우혈류차단후발생하는골두변형의발달과정을연구하는데매우유익하였다. 그러나병변의육안적및방사선학적유사성은돼지의몸무게가가벼운시기까지였으며골성장완료기 ( 술후 20 주 ) 에는과도한몸무게 ( 평균 107 kg) 로인하여이미약화된골두와비구가붕괴되고골두는심하게평편화되어버리는약점이있었다. The Puppy Model 5) 1. 실험목적 Piglet model 에서는대퇴골두의 4 대변형 (coxa plana, coxa magna, coxa vara, subluxation) 을육안과방사선소견을중심으로관찰또는계측하였으나, puppy model 에서는 1 수술방법을다양하게하고, 2 골두골단뿐아니라대퇴골의근위 physis 와 metaphysis 에대하여서도관찰하고, 3 microscopic finding 을첨가하여관찰하였다. 2. 실험방법 출생후 7-9 주 ( 체중 1.5-2.5 kg) 된 68 마리의 mongrel, weaned puppies 을사용하였다. 68 마리중 22 마리는실험에서제외되었다. 이들 22 마리는후방탈구 3 마리, 감염발생 5 마리그리고실험초기사망 14 마리였다. 실험에사용된 46 마리는 Table 3 에기록된바와같이 2 주에서 5 개월까지주기적으로도살하였다. 수술방법은 46 마리를 3 가지서로다른방법으로나누어시행하였다. 12 마리는관절낭의단순절개군 (Group A), 18 Table 3. Puppy Groups according to Extent of Surgery and Postoperative Duration Groups/ Postoperative Period 2 Weeks 1 Month 2 Months 5 Months Total (A) Capsular Incision Only 3 3 3 3 12 (B) Division of Ligamentum Teres Only 4 4 5 5 18 (C) Division of Both Ligamentum Teres and 3 4 5 4 16 Retinacular Artery Total 46 Table 4. Macroscopic, Radiologic and Microscopic Examinations of the Femoral Head and Neck Anatomic Location Macroscopic Findings Radiological Findings Microscopic Findings Articular Color Shape Number of Chondrocytes Cartilage Irregularity Irregularity of Surface Grouping Phenomenon Irregularity of Surface Ossific Coxa Magna Cystic Change Number of Hematopoietic Cells Nucleus Shape Density Vascularity Epiphyseal Height Viability of Trabeculae Shape Degenerative Change of Marrow Space Size Repair Process Physis Anteversion Shortening Fibrillation of Chondrocyte Column Coxa Magna Microcystic Change Medial Bowing Disruption of Chondrocyte Column Shortening of Neck Leg Length Discrepancy Metaphysis Medial Bowing Femoral Neck Shaft Angle Number of Hematopoietic Cells Medial Bowing Vascularity Viability of Trabeculae Degenerative Change of Marrow Space Repair Process 268 www.hipandpelvis.or.kr

Sung-Man Rowe: Animal Experiment of Legg-Calve-Perthes Disease in Piglets, Puppies and Growing Rabbits 마리는 ligamentum teres 절단및고관절의일시적아탈구 (Group B) 그리고나머지 16 마리는 ligamentum teres 와 eipphyseal artery 모두를절단 (Group C) 하였다 (Table 3, 4). 수술후에는주기적으로양측고관절의 X- 선촬영을 2 주간격으로시행하였다. 도살후에는양대퇴골을적출하고 10% formaline solution 에보관하였다. 수술방법은 ZoletilS (7.5 mg/kg of tiletamine and 7.5 mg/kg zolazepam) 을정맥주입하여전신마취를시행하고 좌측고관절의전내방에약 3 cm 정도의피부절개를가하였다. Pectineus muscle 과 femoral neurovascular bundle 사이의간격을분리하여고관절의전방관절낭을노출시켰다. Group A 에서는단순히전방관절낭을수직절개하였고, Group B 는관절낭을절개하고고관절아탈구상태에서 ligamentum teres 을절단한후원상정복하였으며, Group C 는관절낭절개후 ligamentum teres 를절단하고대퇴골두를탈구시키어대퇴경부를철사로감은뒤열을가 C A B D Fig. 3. (A) Radiography of the extractred femurs from a puppy of Group C at postoperative two months showing a decrease in epiphyseal height and cystic changes of the ossific nucleus at left operated femur. (B) Macroscopic photography showing shortening of 2.5 mm with a mild degree of medial bowing of the femoral neck at left operated femur. (C-D) Macroscopic appearances of both extracted femurs five months after operation showing remarkable increase in anteversion and coxa magna of the operated left femur. Table 5. Presence (+) or Absence (-) of Abnormal Findings of the Femoral Head and Neck in Three Experimental Groups in Puppy Model Postperativ/ Macroscopic Abnormalities Radiological Microscopic Abnormalities Group Period Abnormalities Articular Head Neck Leg Length Head Neck Articular Ossific Physis Metaphysis Cartilage Discrepancy Cartilage Nucleus 2 Weeks A - - - - - - + - - - B + - - - + - + + - - C + - - - + - + + - - 1 Month A - + - - - - + - - - B + + - - + - + + - + C + + + - + - + + + + 2 Months A - + - - - - + - - - B + + + + - - + + - - C + + + + + + + + + + 5 Months A - + - - + - + - - - B + + + + + - + - - - C + + + + + + + + Repair Repair www.hipandpelvis.or.kr 269

하여 epiphyseal artery 의혈류를차단하였다. 시술후에는탈구된관절은해부학적위치로정복하고관절낭을완전봉합하여탈구를예방하였다. 수술후 5 일동안 gentamycin 1 mg/kg/day 를근육주사하였다. 3. 실험결과 Ligamentum teres 만의절단군 (Group B) 과중복혈행차단군 (Group C, ligamentum teres 와 rertinacular artery 동시차단군 ) 에있어서모두저명한대퇴골두의변형을보였으나, 중복차단군 (Group C) 에서단독차단군 (Group B) 에비하여골두변형의빈도와 severity 가보다저명하였다 (Fig. 3) (Table 5). 4. 실험결론 체구가적은일부의애완용강아지를대상으로대퇴골두에가는혈류의흐름을차단하였던바 LCPD 환자에서관찰되는것과유사한형태학적변화를관찰할수있었다. The Growing Rabbit Model 11) 1. 실험목적 LCPD 의원인과병리에대한많은연구에도불구하고 LCPD 골두변형의 pathogenesis 는아직도불분명하다. 그러나병의초기에발생하는대퇴골두의측방아탈구 (subluxation) 가대퇴골두변형의주된원인이라는데에는이견이없다. 그러나 LCPD 는사망에이르는병이아니며환부를수술한다하더라도골두를직접다루지는않기때문에골두병변의과정을육안적으로관찰한논문은찾아보기어렵다. 그럼으로비록 subluxation 이골두변형의주된원인이라할지라도이를실험적으로입증한논문은매우드물다 7). 저자는아탈구가대퇴골두의변형에어떠한영향을미치는가를규명할목적으로성장기가토의골두혈행을차단하고동측슬관절을신전위석고고정하여아탈구를유발하였다. 2. 실험방법 출생후 4-5 주 (500-600 g) 된 72 마리의어린토끼를사용하였다. 좌측고관절을실험하였으며우측고관절을대조군으로하였다. 대퇴골두골단으로의혈류차단은돼지와강아지에서와마찬가지로 ligamentum teres 의절단과대퇴경부의결찰 (epiphyseal artery 차단 ) 을병행하였다. 본실험에서는아탈구가골두의병변에어떠한영향을미치는지를알기위하여 Michelsson 과 Lagenskiöld 가제안한것처럼환지의슬관절을신전석고고정하였다 13). 실험군은 3 군으로나누어 Group A 는혈류차단과슬관절고정을시행한경우, Group B 는혈류차단만시행하고슬관절은자유롭게방치한경우, Group C 는혈류차단없이슬관절의신전위고정만시행하였다. 처치후 2 주간격으로양측고관절의 X- 선사진을촬영 (A-P and frog-lateral view) 하고 1 주에서 12 주사이에도살하였다 (Table 6). 도살후양대퇴골을적출하여육안으로그리고방사선학적으로관찰하고조직검사를위하여 10% formalin 용액에보관하였다. 수술은전신마취하에시행하였다. 전신마취는 Zoletil(50 mg/kg Tiletamine and 50 mg/kg Zolazepam) 과 Ketamin(50 mg/kg Ketamine hydrochloride) 을근육주사하였다. 피부절개는대퇴골대전자부에횡으로약 2 cm 절개하여 gluteal muscle 과 short external rotator muscle 을분리한후고관절의후방관절낭을노출시켰다. 노출된관절낭은비구연을따라횡으로절개한후후지를내전및굴곡시키어대퇴골두가후방으로아탈구되면, 이때에 ligamentum teres 을절단하였다. 대퇴골두는후방탈구시키어 3-0 silk 로대퇴경부를강하게감아결찰함으로써경부의혈류를차단하였다. 탈구는다시정복하고피부는봉합한후 gentamycin 1 mg/kg 을근육주사하였다. 3. 실험결과 주기적으로촬영한 X- 선사진과적출한대퇴골의관찰결과육안과 X- 선소견에서각각 6 가지의이상소견 ( 변형 ) 을관찰하였다. 이러한변형의빈도와중등도를실험군별로비교검토하였던바 Group A 군에서 Group B 또는 Group C 보다 Overall incidence of deformity (P<0.001), head deformity score (P<0.001) 그리고 incidence of a Table 6. Rabbit Groups according to the Vascular Interruption and the Cast Immobilization of the Knee Weeks after Experimental Procedure Group N 1 2 4 8 12 (A) Operation + Cast 25 4 6 5 6 4 (B) Operation Only 25 4 5 6 5 5 (C) Cast Only 22 4 5 4 4 5 270 www.hipandpelvis.or.kr

Sung-Man Rowe: Animal Experiment of Legg-Calve-Perthes Disease in Piglets, Puppies and Growing Rabbits total collapse of the capital femoral epiphysis 가모두높았다 (Fig. 4) (Tables 7-10). A B C D Fig. 4. (A) Radiograph before surgery showing normal hip of 5 week-year-old rabbit. (B) Radiograph at postoperative 4 weeks showing coxa vara and greater trochanter (GT) overgrowth. (C) Radiograph at 12 weeks showing further increase of deformities. (D) Macroscopic finding of extracted femur showing coxa magna, coxa vara, and GT overgrowth. Table 7. Radiological and Macroscopic Abnormalities A B C Abnormal Findings Operation Operation Cast P-value + Cast Only Only Radiologic Findings Height Decrease of Ossific Nucleus 016 011 00 Coxa Vara 019 011 00 Epiphyseal Fragmentation or Cystic Change 007 007 00 Total Epiphyseal Collapse 009 001 00 Greater Trochanter Overgrowth 013 011 00 Acetabular Dysplasia 018 008 04 Macroscopic Findings Articular Surface Flattening 021 010 00 Articular Surface Irregularity 021 010 01 Severe Collapse of Femoral Head and Neck 009 001 00 Coxa Magna (>0.2 mm) 022 011 13 Anteversion or Retroversion 018 010 05 Leg Length Discrepancy (>1 mm) 016 018 05 Total 189 109 28 Average (Total/Number of Rabbits) 7.6 4.4 1.3 <0.001 Table 8. Mean Head Deformity Score (HDS) after Procedures in Experimental Groups Head Deformity Score Group 1+2 Wks 4 Wks 9+12 Wks Total P-value (A) Operation+Cast 2.7 (10) 5.3 (5) 6.6 (10) 4.9 0.004 (B) Operation Only 0.2 (9)0 1.3 (6) 4.3 (10) 2.4 0.002 (C) Cast Only.0 (9) 0.3 (4) 0.6 (9)0 0.3 0.071 P-value 0.007 0.029 <0.001 <0.001 * Numbers in parentheses are sample sizes. www.hipandpelvis.or.kr 271

Table 9. Distribution of 10 Hips Showing Severe Collapse of Femoral Head and Neck in Experimental Groups Group Total N* of Rabbits Total N of Rabbits Head Status Rabbits with with Severe Collapse Severe Collapse (A) Operation + Cast 25 9 (36%) Contained (n=9) 2 (22%) Dislocated (n=16) 7 (44%) (B) Operation Only 25 1 (4%)0 Contained (n=17) 1 (6%)0 Dislocated (n=8) 0 (0%)0 (C) Cast Only 22 0 (0%)0 Contained (n=22) 0 (0%)0 Dislocated (n=0) 0 (0%)0 * N: Number. Table 10. Head Deformity Scores (HDS) and Number of Severe Collapse of Femoral Head and Neck in 20 Rabbits Devascularized (Both Group A and B) and Sacrificed at 8 and 12 Weeks Acetabulo-Femoral Total Head Severe Collapse Relationship N* of Deformity Score of Femoral Head Rabbits Mean Range and Neck Fully Contained 05 4.4 3-5 0 Partially Contained 10 5.5 3-7 3 (Subluxated) Dislocated 05 7.2 6-8 5 P=0.006, γ=0.863. * N: Number. 4. 실험결론 본실험에서는대퇴골두의아탈구가더욱빈번하고더욱심한골두변형을유발함을확인함으로 LCPD 의치료에있어서 subluxation 을예방하여야골두변형을예방할수있음을알게되었다. REFERENCES 01.Catterall A. The natural history of Perthes disease. J Bone Joint Surg Br. 1971;53:37-53. 02.Babyn PS, Kim HK, Gahuunia HK, et al. MRI of the cartilaginous epiphysis of the femoral head in the piglet hip after ischemic damage. J Magn Reson Imaging. 1998; 8:717-23. 03. Kim HK, Su PH. Development of flattening and apparent fragmentation following ischemic necrosis of the capital femoral epiphysis in a piglet model. J Bone Joint Surg Am. 2002;84-A:1329-34. 04.Rowe SM, LEE JJ, Chung JY, Moon ES, Song EK, Seo HY. Deformity of the femoral head following vascular infarct in piglets. Acta Orthop. 2006;77:33-8. 05.Rowe SM, Moon ES, Jung ST, Kim JW, Kim JS, Kim MS. Experimental study of avascular necrosis of the femoral head in the puppy. J Korean Orthop Assoc. 2003;38:447-53. 06.Sanchis M, Zahir A, Freeman MA. The experimental simulation of Perthes disease by consecutive interruptions of the blood supply to the capital femoral epiphysis in the puppy. J Bone Joint Surg Am. 1973;55:335-42. 07.Kamegaya M, Shinada Y, Akita T, Ogata S, Someya M, Tsuchiya K. Experimental avascular necrosis of the femoral capital epiphysis and induced subluxation of the hip in young rabbits. J Pediatr Orthop. 1990;10:1-5. 08.Lemoine A. Vascular changes after interference with the blood flow of the femoral head of the rabbit. J Bone Joint Surg Br. 1957;39-B:763-77. 09. Rösingh GE, James J. Early phase of avascular necrosis of the femoral head in rabbits. J Bone Joint Surg Br. 1969; 51:165-74. 10.Rowe SM, Chung JY, Moon ES, Jung ST, Lee HJ, Lee JJ. The effects of subluxation of the femoral head with avascular necrosis in growing rabbits. J Pediatr Orthop. 2004;24:645-50. 11.Rowe SM, Park SK. Necrosis of femoral head in growing rabbit. J Korean Orthop Assoc. 1986;1:29-34. 12.Yoshiwara S. An experimental study of ischemic damage and repair on the femoral head epiphysis in growing rabbits. Nihon Seikeigeka, Gakkai Zasshi. 1994;68:978-89. 13.Michelsson JE, Langensklöld A. Dislocation or subluxation of the hip. Regular sequels of immobilization of the knee in extension of young rabbits. J Bone Joint Surg Am. 1972;54:1177-86. 272 www.hipandpelvis.or.kr