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1 대한내과학회지 : 제 94 권제 3 호 Interpretation of diagnostic test 골밀도검사의실제 : Dual-Energy X-ray Absorptiometry (DXA) 중심으로 부산대학교병원내분비대사내과 김은희ㆍ김인주ㆍ전윤경 Measurement and Interpretation of Dual-Energy X-ray Absorptiometry Bone Density Measurements Eun Heui Kim, In Joo Kim, and Yun Kyung Jeon Division of Endocrinology, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea Dual-energy X-ray absorptiometry (DXA) is a widely used technology used to diagnosis osteoporosis and monitor changes in bone mineral density (BMD). The present paper reviews the clinical application of DXA in evaluating osteoporosis, including indications for BMD testing, interpretation of DXA results, diagnosis of osteoporosis, and serial BMD follow up. As the clinical utility of DXA depends on the quality of the scan acquisition, the precision assessment of DXA is also discussed. (Korean J Med 2019;94: ) Keywords: Osteoporosis; Diagnosis; Bone mineral density; Dual-energy X-ray absorptiometry 서론전세계적으로노령화가급속히진행되고있으며, 대한민국도 2026년초고령사회에도달할것으로예측하고있다. 이와더불어노령화와관련된질환이관심의대상이되고있으며대표적인질환중하나가골다공증이다. 2017년대한골대사학회와국민건강보험공단이발표한 2017 한국인골다 공증및골다공증골절 Fact Sheet [1] 에서는 50세이상여성의 37%, 남성의 7.5% 에서골다공증이발생함을보고하였으며, 골감소증의발생비율은남 여각각 46%, 48% 로 2명중 1명이골감소증인것으로보고하였다. 또한여성에서는연령이 10세증가할때마다골다공증이 2배씩증가하여 70세이상여성은 68.5% 가골다공증환자이며, 2008년이후 2013년까지골다공증골절발생률이매년 4% 씩증가하는것으로 Received: Revised: Accepted: Correspondence to Yun Kyung Jeon, M.D., Ph.D. Division of Endocrinology, Department of Internal Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea Tel: , Fax: , puritystar@hanmail.net Copyright c 2019 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - Eun Heui Kim, et al. Clinical practice of BMD measurement - 보고하였다 [1]. 골다공증은골량의감소와미세구조의이상을특징으로하는전신적인골격계질환으로서결과적으로 뼈가약해져서부러지기쉬운상태가되는질환 으로정의하고있다 [2]. 세계보건기구 (World Health Organization, WHO) 에서는 골다공증 이라는용어를, 폐경후여성과 50세이상의남성을대상으로한정하여골밀도검사상 T-점수가 -2.5 이하인경우로정의하고있으며, 50세이하의남성과폐경전여성에서는 Z-점수 -2.0을기준으로 연령기대치이하또는연령기대치이내 로진단하고있다 [3,4]. 현재골밀도를측정하는방법은초음파검사 (quantitative ultrasonography, QUS), 정량적전산화단층골밀도검사 (quantitative computed tomography, QCT), 말단골골밀도검사 (peripheral quantitative computed tomography, pqct) 등이다양하게이용되고있다. 그러나 QUS의경우골다공증골절의발생예측에는사용할수있지만정밀도가낮아서약물치료에대한반응을판단하기어렵고, 중심골 QCT의경우민감도가높아 t값으로진단하면과잉진단을할수있어기준을 mg/cm 3 로진단해야하며, 현재척추골밀도에대한값만우리나라보험에서인정된다. 따라서본논문에서는이중에너지엑스선흡수계측법 (dual energy X-ray absorptiometry, DXA) 을이용한골밀도검사에한정하여골밀도검사의실제에대하여알아보고자한다. 본론 경우 ), 3) 비정상적으로 1년이상무월경을보이는폐경전여성, 4) 비외상성 (fragility) 골절인경우, 5) 골다공증을유발할수있는질환이있는경우, 6) 골다공증을유발할수있는약물을복용중이거나장기간 (3개월이상 ) 투여계획이있는경우, 7) 기타골다공증검사가반드시필요한경우골밀도검사를인정하고있다 (Table 1). 이번개정에서여섯번째항목인골다공증을유발할수있는약물복용에 장기간 (3개월이상 ) 투여계획이있는경우 가추가되었다. 검사는진단시 1회인정하며, 말단골골밀도검사결과추가검사의필요성이있는경우 1회에한하여중심골 ( 척추, 고관절 ) 에서추가검사를인정한다. 추적검사의실시간격은 1년이상으로하되, 검사결과정상골밀도로확인된경우는 2년으로한다. 치료효과판정을위한추적검사는중심골에서실시한경우에한하여인정한다. 다만스테로이드를 3개월이상복용하거나부갑상선기능항진증으로약물치료를받는경우, 정상골밀도인경우첫 1년에 1회, 이후부터는 2년에 1회골밀도검사를진행하도록인정한다. T-점수가 -3.0 이하인경우, 첫 1년은 6개월에 1회이후부터는 1년에 1회실시하도록한다. 고시제 호에서추가된부분은임신과연관된골다공증성 (pregnancy & lactation associated osteoporosis) 골절이의심되는경우 6개월간격으로 2회, 환자의장기부재, 진료일정등불가피한사유로추적검사실시간격을충족하지못하는경우 4주범위내에서인정한다는점이다. 또한만 10세이상-만 18세미만의소아를분리, 골 골밀도검사의적응증세계임상골밀도측정학회 (International Society for Clinical Densitometry, ISCD) 에서는 65세이상의여성과 70세이상의남성에서골밀도검사를권고하고있으며, 65세미만의여성과 70세미만의남성이더라도저체중, 이전의골절력, 골다공증을유발할수있는질환이있거나약물을복용중인경우, 골감소를유발할수있는질환이나상태에있는경우, 골다공증치료를시작하거나치료효과를판정하기위한경우골밀도측정을권고하고있다 [5]. 최근개정된국내보험 ( 고시제 호 ) 에서도만 18세이상성인을대상으로 1) 65세이상여성과 70세이상남성, 2) 고위험요소가 1개이상있는 65세미만의폐경후여성 ( 고위험요소는체질량지수 < 18.5 kg/m 2 인경우, 비외성성골절의과거력이있거나가족력이있는경우, 외과적수술로인한폐경또는 40세이전의자연폐경인 Table 1. Indication for BMD Insurance standards for bone Mineral density testing Adults aged over 10 years 1) Women aged over 65 and men over 70 2) post-menopausal women younger than age 65 who has more than 1 risk factor 3) Premenopausal women with abnormal amenorrhea for more than one year 4) in case of fragility fractures 5) If you have a disease that can cause osteoporosis 6) If you are taking medication that can cause osteoporosis or you plan to take it for a long time (3 months or more) 7) Other tests for osteoporosis are necessary ** high risk factors i) body mass index < 18.5 kg/m 2 ii) history or family history of fragility fracture iii) menopause before age 40 due to surgical or natural causes BMD, bone mineral density

3 - 대한내과학회지 : 제 94 권제 3 호통권제 688 호 밀도검사의국내소아 청소년참고치가있는 [ 다334가 ] 양방사선 ( 광자 ) 골밀도검사 (DXA) 를이용한골밀도측정을인정한다는것이신설되었다. 골다공증을유발할수있는질환이있는경우, 골다공증을유발할수있는약물을복용중이거나장기간 (3개월이상 ) 투여계획이있는경우, 기타골다공증검사가반드시필요한경우시행하도록하며, 급여횟수는진단시 1회, 추적검사는 Z-점수 > -1.0인경우 2년에 1회, -2.0 Z-점수 -1.0인경우 1년에 1회, Z-점수 < -2.0인경우첫 1년은 6개월에 1회, 그이후부터는 1년에 1회로인정하고있다. 특히 1년이상의간격으로골밀도를측정하도록하는규정이환자의장기부재, 진료일정등불가피한사유로추적검사실시간격을충족하지못하는경우 4주범위내에서인정하도록변경된것은환자중심의의료환경을만들기위한노력의결과라할수있겠다. 골밀도측정정밀도측정 DXA로골밀도를측정하는경우기계의정밀오차를확인 해야하며검사자는검사술기를습득하고 100명의환자를대상으로훈련과정을거친뒤정밀도를검사한다. ISCD에서는무작위로환자를선발하여 15명을 3번측정하거나 30명을 2번측정하여정밀도를검사하도록하고있으며, 재측정시환자는반드시검사대에서내려왔다가다시올라가게하여자세를재조정하도록한다 [5]. 보정 (calibration) 을위해서척추팬텀을사용하며, 팬텀은칼슘하이드록시아파타이트 (calcium hydroxyapatite) 재질로인체와유사한 3가지조건 ( 저밀도-정상-고밀도 ) 으로된척추의모양으로만들어져있다. ISCD에서는보정을위하여최소 1주에 1회팬텀스캔을권고하고있다. 또한 DXA 하드웨어가변경된경우또는동일한기술을갖춘시스템이교체된경우교차보정 (cross calibration) 을수행하여시스템과의정량적비교를허용할것을권장하고있다. 교차보정은교체전과후팬텀을이용하여 10회씩측정한후평균골밀도의차이가 1% 이상인경우제조업체에수정을요구하도록한다 [6]. 그외에도실제 DXA를측정하고결과를해석, 보고할때에는여러가지주의해야할점이있으며, ISCD에서는각각의단계에서주의해야할점을표로정리하여체크하도록권고하고있다 (Table 2) [7]. Table 2. Best practices for DXA measurement and reporting: ISCD [7] DXA best practice: scan acquisition and analysis 1.1. At least one practicing DXA technologist, and preferably all, has a valid certification in bone densitometry Each DXA technologist has access to the manufacturer s manual of technical standards and applies these standards for BMD measurement Each DXA facility has detailed SOPs for DXA performance that are updated when appropriate and available for review by all key personnel The DXA facility must comply with all applicable radiation safety requirements Spine phantom BMD measurement is performed at least once weekly to document stability of DXA performance over time. BMD values must be maintained within a tolerance of ± 1.5%, with a defined ongoing monitoring plan that defines a correction approach when the tolerance has been exceeded Each DXA technologist has performed in vivo precision assessment according to standard methods and the facility LSC has been calculated The LSC for each DXA technologist should not exceed 5.3% for the lumbar spine, 5.0% for the total proximal femur, and 6.9% for the femoral neck. DXA best practice: interpretation and reporting 2.1. At least 1 practicing DXA interpreter, and preferably all, has a valid certification in bone densitometry The DXA manufacturer and model are noted on the report The DXA report includes a statement regarding scan factors that may adversely affect acquisition/analysis quality and artifacts/confounders, if present The DXA report identifies the skeletal site, region of interest, and body side for each technically valid BMD measurement There is a single diagnosis reported for each patient, not a different diagnosis for each skeletal site measured A FRAX is used appropriately When reporting differences in BMD with serial measurements, only those changes that meet or exceed the LSC are reported as a change. DXA, dual-energy X-ray absorptiometry; ISCD, International Society for Clinical Densitometry; BMD, bone mineral density; SOPs, standard operating procedures; LSC, least significant change; FRAX, fracture risk assessment tool

- 김은희외 2 인. 골밀도검사의실제 - 검사전확인사항 DXA에의한방사선노출은매우적어일반적인하루환경방사선과비슷한정도이다. 그러나매우적은양이지만이온화방사선이사용되므로검사전에는임신여부를확인해야하며, 임신시에는검사를시행하지않는다. 검사전조영제를사용한경우, 스캔된부위에이물질이있는경우에도골밀도에영향을미칠수있으므로미리제거하도록한다 [5].

4 - 김은희외 2 인. 골밀도검사의실제 - 검사전확인사항 DXA에의한방사선노출은매우적어일반적인하루환경방사선과비슷한정도이다. 그러나매우적은양이지만이온화방사선이사용되므로검사전에는임신여부를확인해야하며, 임신시에는검사를시행하지않는다. 검사전조영제를사용한경우, 스캔된부위에이물질이있는경우에도골밀도에영향을미칠수있으므로미리제거하도록한다 [5]. 골밀도결과지해석골밀도검사가제대로이루어졌는지우선골영상을확인한다척추의경우척추가영상의가운데위치하는지, 일직선으로유지되는지확인한후, 양쪽의장골능 (iliac crest) 이살짝보이면서네번째요추의 X shape 이보이는지 12번째늑골 (rib) 이살짝보이는지확인한다. 고령으로갈수록퇴행성변화나시술로인한인공삽입물이골밀도에영향을주는경우가많으므로주의깊게살펴야한다. 대체로요추는 1번에서 4번으로갈수록골밀도가증가하는경향이있다. 만약위쪽요추가더높은값을보이거나, 인접한척추보다 T-점수가 1 이상높게측정되는경우이부위의오류인자를파악하고이부위를제외한척추값의평균을채택하도록한다. 만약 판정가능한요추가하나인경우결과는판정불가로판독하여야한다. 대퇴골의경우검사시다리를 내전 (adduction) 하여소전자부 (lesser trochanter) 가약간보일정도가되어야하며, 영상의세로축에대퇴골이일직선으로곧게위치하였는지확인해야한다 (Fig. 1) [8]. 골다공증의진단 WHO가제시하여현재까지이용되고있는골다공증의진단기준은환자의고관절부위, 요추부혹은전완부 (forearm) 골밀도를측정하여젊은백인성인대조군의정상평균값과비교하여산출된표준편차를 t값으로표기한것이다 (Table 3) [3,4]. WHO 의진단기준에서는몇군데의골밀도를측정하는지와관심영역 (region of interest, ROI) 설정에관한구체적인기준을제시하지않았으므로 ISCD 에서는다음과같이제안하였다. 척추부위와고관절부위를모두측정하는것을원칙으로하되, 척추는두부위이상의평균값을기준으로한다. 고관절의경우근위대퇴골 (total proximal femur), 대퇴골경부 (femoral neck) 를각각측정하여가장낮은골밀도를결과로진단한다. Ward 부위는진단에사용할수없다. 척추와고관절부위를측정할수없거나해석이어려운구조적문제가있는경우, 부갑상선기능항진증환자나, DXA 측정테이블의무게하중을초과한비만의경우, 비우세한쪽의 (non-dominant) 전완부의요골원위 33% 부위 (one-third radius) 골밀도를진단에사용할수있다 [9]. 골밀도의추적검사 Figure 1. Appropriate positioning for BMD of the femur [8]. BMD, bone mineral density. Table 3. Diagnosis of osteoporosis [3] Definition Category Normal T-score -1.0 Osteopenia -2.5 < T-score < -1.0 Osteoporosis T-score -2.5 Severe osteoporosis T-score -2.5 and fragility fracture 골밀도추적검사의경우이전검사와동일한자세로동일한관심영역 (ROI) 을동일한촬영모드와스캔분석으로시행해야한다. 예상되는골밀도변화가골밀도측정장비고유의최소한의의미있는변화 (least significant change, LSC) 이상으로변화된경우의미있는변화라고판단하며, 치료효과나시기를결정하는데도움이된다. LSC 는각기관에서직접측정한자료를바탕으로얻은분산계수 (coefficient of variance) 에 2.77 (95% 유의수준 ) 을곱한값으로 ISCD는척추의 LSC는 5.3% ( 정밀오차 1.9%), 대퇴골전체골밀도는 5.0% ( 정밀오차 1.8%), 대퇴골경부는 6.9% ( 정밀오차 2.5%) 이내가되도록권고하고있다 [7]

5 - The Korean Journal of Medicine: Vol. 94, No. 3, 결 DXA를이용한골밀도검사시여러가지문제점이있을수있다. 환자의체형이비만으로지방량이많은경우골밀도가높게측정될수있고, 골밀도측정시자세또한결과의정확성에영향을미칠수있다. 검사자의숙련도가정확도에영향을줄수있다는한계를가지고있음에도불구하고 [10,11], 현재까지 DXA는골밀도측정의표준화된방법으로받아들여지고있다 [12]. 검사과정중발생할수있는여러문제점과정도관리를위해서는검사팀과긴밀한협조가필요하다. 얻어진이미지의적정성을확인하고, 판독하는노력을통하여정확한골다공증의진단과치료효과판정이가능할것으로생각된다. 또한골밀도이외의검사들, 골표지자검사나칼슘, 비타민 D 등의혈청학적검사를병행한다면골다공증을일으키는이차적원인을찾거나, 부족한성분을보충해줄수있는기회가되어더나은의료를제공할수있을것으로기대한다. 중심단어 : 골다공증 ; 진단 ; 골밀도 ; 이중에너지엑스선흡수계측법 론 REFERENCES 1. Korean Society for Bone and Mineral Research. Korean Osteoporosis and Osteoporotic fracture Fact Sheet [Internet]. Seoul (KR): Korean Society for Bone and Mineral Research, c2017 [cited 2019 May 1]. Available from: data/board_notice/ pdf. 2. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001;285: Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994;9: WHO Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1994;843: Shepherd JA, Schousboe JT, Broy SB, Engelke K, Leslie WD. Executive summary of the 2015 iscd position development conference on advanced measures from DXA and QCT: fracture prediction beyond BMD. J Clin Densitom 2015;18: Shepherd JA, Lu Y, Wilson K, et al. Cross-calibration and minimum precision standards for dual-energy X-ray absorptiometry: the 2005 ISCD Official Positions. J Clin Densitom 2006;9: Lewiecki EM, Binkley N, Morgan SL, et al. Best practices for dual-energy X-ray absorptiometry measurement and reporting: international society for clinical densitometry guidance. J Clin Densitom 2016;19: Korean Society for Bone and Mineral Research Committee on the compilation of guidelines. Korea Osteoporosis Treatment Guideline 2018 [Internet]. Seoul (KR): Korean Society for Bone and Mineral Research Committee on the compilation of guidelines, c2018 [cited 2019 May 1]. Available from: ce=web&cd=2&ved=2ahukewj1l878lfzhahws7gekhc wocggqfjabegqiaxac&url=http%3a%2f%2fwww.m don.co.kr%2fnews%2fdownload.html%3fno%3d20841%2 6atno%3D66938&usg= AOvVaw2Ars6cBfOC2-Mb9bn9KbKJ. 9. Leib ES, Lenchik L, Bilezikian JP, Maricic MJ, Watts NB. Position statements of the international society for clinical densitometry: methodology. J Clin Densitom 2002;5 Suppl: S5-S Watts NB. Fundamentals and pitfalls of bone densitometry using dual-energy X-ray absorptiometry (DXA). Osteoporos Int 2004;15: Messina C, Bandirali M, Sconfienza LM, et al. Prevalence and type of errors in dual-energy X-ray absorptiometry. Eur Radiol 2015;25: Sözen T, Özışık L, Başaran NÇ. An overview and management of osteoporosis. Eur J Rheumatol 2017;4:

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<4D F736F F F696E74202D20B1E8B0E6B9CE5F FBAD0B4E7BCADBFEFB4EBBAB4BFF8B3BBB0FABFACBCF6B0ADC1C25FBFC3B9D9B8A5B0F1B9D0B5B5C0C720C6C7B5B6205BC0D0B1E220C0FCBFEB5D> 골밀도검사의올바른판독 분당서울대학교병원내분비내과김경민 Osteoporosis Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Normal bone