Geriatric Rehabilitation 2016;6:48-54 Review Article 뇌졸중후골다공증환자의임상양상 유승돈 경희대학교의과대학재활의학교실 The Clinical Manifestations of Osteoporosis in the Patients w

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1 Review Article 뇌졸중후골다공증환자의임상양상 유승돈 경희대학교의과대학재활의학교실 The Clinical Manifestations of Osteoporosis in the Patients with Cerebral Stroke Seung Don Yoo, M.D., Ph.D. Department of Physical Medicine and Rehabilitation, Kyunghee University College of Medicine, Seoul 05278, Korea Abstract Stroke patients have high prevalence of osteoporosis and fracture. Low bone mineral density (BMD) and fracture may contribute to further functional loss. Osteoporosis after stroke can be produced by a complex interaction of factors. Poststroke osteoporosis is currently not adequately recognized and treated. Bone fracture in stroke patients occurs at different times during the recovery phase, prolonging recovery time. Most poststroke bone fractures occur in the lower extremities. Motor changes, including posture, mobility, and balance contribute to bone loss and thus increase risk of bone fracture. Approximately one in seven hip fractures occurs in older stroke survivors and is associated with poorer outcomes. Early application of fracture prevention strategies is needed. Guidelines for osteoporosis diagnosis and management do not include poststroke osteoporosis. Management of poststroke osteoporosis should start with a careful and comprehensive risk assessment. Vitamin D intake may prevent osteoporosis and fractures in patients with stroke. Drugs show some benefits in preventing osteoporosis, but additional clinical trials are needed to determine the most effective conditions for post-stroke application. Key Words Osteoporosis, Cerebral stroke 접수일 : 2016년 8월 15일게재승인일 : 2016년 8월 29일교신저자 : 유승돈주소 : 서울시강동구동남로 892번지강동경희대학교병원재활의학과 Tel : Fax : kidlife@khu.ac.kr 서론 전세계적으로인구집단의나이가증가함에따라뇌졸중은주요사망원인이되고있다. 뇌졸중의유병률은 60-79세의남자에서 6.1% 이며 80세이상에서는 15.8%, 60-79세의여자는 5.2%, 80세이상의여자는 14% 이다. 1 한국에서는매년 105,000명의뇌졸중환자가새로이또는재발하며뇌졸중으로 26,000명이사망한다 년한국의국민건강영양조사에따르면뇌졸중환자의 60% 이상이감각장애, 운동장애와 같은장기적후유증을가지고있다. 3 골다공증은골량의감소와골조직미세구조의변화로골절에대한감수성이증가되는전신성질환이다. 골다공증은원인, 발병연령, 임상적특성에따라일차성과이차성골다공증으로분류된다. 뇌졸중으로인한편마비환자에서는여러요인으로골다공증이발생한다. 우선마비로인한운동제한, 부동과불용에의해골흡수가증가하며골의체중부하감소로인하여골무기질화에장애가생긴다. 둘째로삼킴장애, 영양소섭취부족과일광노출부족에의한비타민 D 결핍이일어 48

2 나고이에대한보상작용으로이차성부갑상선기능이항진되어골흡수가증가함에따라골밀도가더욱감소한다. 뇌졸중환자의골밀도감소는균형장애, 협응력장애, 하지근력저하와관련이있으며, 특히노인환자의낙상과그로인한대퇴골골절의위험을가중시킨다. 4-6 뇌졸중환자의골다공증에대한관심은골절이발생했을때특히대퇴골골절이발생할때높다. 7 50대의여자뇌졸중환자에서대퇴골골절위험성은 11배나높으며 6 같은연령대의일반인과비교해도뇌졸중환자에서대퇴골골절발생이 1.5 배에서 4배정도높다. 8,9 뇌졸중환자에서골다공증이잘발생하고척추골절, 대퇴골절, 요골골절의발생을증가시켜골절로인한합병증으로재원기간증가, 사망률의증가로의료비의상승을초래할수있다. 따라서본논문에서는뇌졸중후골다공증의임상양상을고찰하여뇌졸중후골다공증치료와골절발생을낮추는데도움이되고자한다. 본론 1) 뇌졸중후골다공증의발생 세계건강기구의진단기준에근거하여골밀도가 2.5 표준편차이하인경우로정의한다. 이때참고치는젊은건강한성인의골밀도즉 T score와비교한다. 일반적으로정상골밀도는 T score -1.0 미만으로정의하며, 골결핍 (osteopenia) 은 T score가 -1.0 이상에서 -2.5 이하인경우, 골다공증은 T score가 -2.5 이하인경우로정의한다. Tomasević -Todorović 등은 10 1년 6개월이상된 40명의뇌졸중환자에서시행한단면연구에서척추골다공증의발생률이건강한일반인은 12.5%, 뇌졸중환자는 42.5% 이며대퇴골골다공증의경우는각각일반인 5%, 뇌졸중환자는 15% 로뇌졸중환자에서골다공증의발생률이현저히높다고보고하였다. Kim 등 11 은 48명의 1개월된뇌졸중환자에서 43.8% 의유병률을보고하였다. 여러연구에서발표되는골다공증의유병률을비교하는것은측정하는위치, 연구에참여하는대상자의나이범위, 대조군의나이에차이가있기때문에단순하지않다. 게다가뇌졸중환자와다른대조군과의비교는더욱어렵다. 그러나뇌졸중의초기에부동으로골흡수가증가하여 골다공증의유병률이증가하고나중에균형문제, 동반되는관절구축, 음식섭취등의영양문제로인하여골다공증의발생이더욱증가한다. 12,13 2) 뇌졸중후비타민 D 결핍뇌졸중환자에서골절의위험성증가와관련하여비타민 D 결핍이중요한인자로작용한다. 비타민 D 결핍은칼슘의흡수, 뼈의기질화, 근력을저해하며근육량의감소와관련이있어서낙상의위험성을높이는데관여한다. 14 비타민 D 결핍은 25-OH D의낮은수치로인해뇌졸중의위험인자가된다. 15 한편비타민 D는뇌졸중환자에서인지기능저해를줄여주어신경관련질환에예방효과가있다고하지만근거가부족한실정이다. 향후비타민 D 치료가사망률과이환율과관련하여뇌졸중의위험성을줄여줄수있는지확증할필요가있다. 비타민 D 보충은뇌졸중골다공증환자에서중요하지만건강한일반인에서는골다공증예방효과에대하여논란의여지가있다. 메타분석에서는골밀도에대한비타민 D의보충의효과가없다고하였으나 16 다른연구에서는칼슘과비타민 D의병용투여로골밀도의의미있는증가가관찰되었으며그로인한낙상의위험을감소시켰다고보고하였다. 17 3) 뇌졸중후골밀도의감소양상 de Brito 등 18 은 57명의 12개월이상된만성편마비환자에서평균 16개월간의골밀도감소에대하여코호트연구를시행한결과마비측전완 (forearm) 부위에서정상측전완부위와비교하여의미있게골밀도가감소되는것을관찰하였다. 대퇴골부위의골밀도는마비측과정상측사이에차이가관찰되지않았다. 대퇴골의골밀도는뇌졸중의이환기간과는상관없이항응고제나항경련제를사용하는경우와경직이심할수록감소되었다. Jørgensen 등 19 은뇌졸중을가진 40명의근위부대퇴골의골밀도변화를연구한결과평균적으로 1년후에정상측은골밀도의변화가없는반면마비측은 3% 가감소됨을보고하였다. Ramnemark 등 20 은 21명의뇌졸중환자를 1, 4, 7, 12개월추적관찰한결과 1개월과 12개월사이의비교에서골밀도가가장많이감소되는부위는마비측상완골 (-17%) 이며그다음으로는마비측근위부대퇴골 (-12%) 이었으며마비가없는근위부대퇴골도 -4% 로의미있는골밀도의감소가관찰되었다. 49

3 65세이상의뇌졸중환자에서골밀도가흔히감소하지만마비측이비마비측과비교하여골밀도감소가더크며골감소증 (osteopenia) 을야기시키는비타민 D 부족이원인기전으로추정된다. 21 골밀도의감소는뇌졸중의급성기에매우빠르게진행되며 22 가장현저한변화는첫수개월에발생한다. 23 전향적인연구로뇌졸중후골밀도의변화양상을고찰한 Borschmann 등 24 은뇌졸중후 6개월에마비측과비마비측사이의골밀도의차이가원위부경골에서 7% 차이가난다고하였다. 다른연구에서는부동 (immobility) 이골밀도의감소를야기시키지만걸을수있는뇌졸중환자에서골밀도에서 3% 감소된다고하였다. 이러한결과를통하여뇌졸중그자체가골밀도의감소를야기시키고뼈의약화를가져오는위험인자라고할수있겠다. 따라서골밀도감소에영향을미치는뇌졸중기전을이해하고예방방법을개발하는더많은연구가진행될필요가있다. (2) 뇌졸중후척추압박골절골다공증으로인한다양한골절가운데척추압박골절은가장흔하며대퇴골골절과는달리증상이없고진단이안되는경우가많다. 중국의베이징여자의척추압박골절의유병률은 50-59세에서는 3.9% 이지만 80세에서는 31.2% 로나이가증가함에따라급격하게증가한다. 31 1개월된 48명의뇌졸중환자에서발병된척추압박골절은 25% 였으며남자는흉추 12번, 흉추 11번, 흉추 6번, 흉추 8번, 요추 4번순이었으며여자환자는요추 1번, 흉추 11번, 12번, 요추 2번순이었고 12 명 (25%) 에서한개이상의골절이있었고두개이상의흉요추골절은 8명 (16.7%) 에서발견되었다. 그리고우연히발견된척추골절로다음해에새로운골절이발생할위험성은 9배나되며다른모든곳의골절발생위험성도 2배나증가하게된다. 32 그러나연구방법에따라다양한결과가도출될수있으며진단방법이중요하다고할수있다. 4) 뇌졸중후골다공성골절 (1) 뇌졸중후골절의위험인자고령, 흡연, 고혈압, 신체활동의감소가뇌졸중후골다공성골절의요인이다. 뇌졸중과뼈의골절의위험인자는서로공통의요인으로작용하며뇌졸중의발생위험이높을수록골다공증과골절의위험성도높다. 뇌졸중환자는뼈골절의위험성이매우높으며 25, 특히노인의높은사망률과관련있는대퇴골골절의위험성은 2배에서 4배나증가하게된다. 26 보행자세, 근골격계에가해지는하중의변화가뇌졸중후건강에주요한위험요인으로생각되며낮은골밀도, 균형장애, 보행장애, 근육변형등도위험요인이다. 27,28 기능제한의정도가낙상의위험성을예측하는데유용하게사용될수있다. 135명의노인뇌졸중환자에서 Nyberg 등 29 은낙상예측을위해저위험, 중간위험, 고위험군으로나누어분석하였다. 낙상의위험성을높이는인자로남자, 일상생활동작수행능력이낮은경우, 요실금, 양측운동능력장애, 불안정한자세, 시공간편측무시, 이뇨제사용, 항우울제사용, 안정제사용등이있다. 29 낙상의위험을평가하기위해전반적인기능평가를수행하는것이뇌졸중후골절발생예측을위해중요하다. 30 (3) 뇌졸중후대퇴골골절 273,000명의뇌졸중환자를대상으로한후향적연구에서 50-54세의여자뇌졸중환자는대퇴골골절위험성이 11배나높으며평균적으로같은연령의일반인과비교하여뇌졸중환자에서대퇴골의발생이 1.5배에서 4배정도로높게증가한다. 6 Ramnemark 등 8 은뇌졸중환자에서대퇴골골절의발생빈도를 4-15% 로보고하였고특히이환측이 79% 이상나타난다고하였다. 60세이상의골다공증고관절골절환자 761명을대상으로한단면적연구에서뇌졸중후고대퇴골골절은 13.1% 의유병률이관찰되었고뇌졸중발생후평균 2.4년에발생하였다. 뇌졸중군에서여자, 치매, 일과성뇌허혈의병력, 고혈압, 관상동맥질환, 이차성부갑상선항진증, 보행도구사용, 시설거주환자에서대퇴골골절이더많이발생하는것으로관찰되었다. 뇌졸중후대퇴골골절환자는비타민 D 결핍이 68%, 과도한골흡수 (bone resorption) 는 90% 관찰되었다. 대퇴골골절이발생되기전에골다골증치료를받은뇌졸중환자는단지 15% 에불과하였다. 33 5) 뇌졸중후골다공증환자의임상양상 Sahin 등 34 은 20일미만의급성기뇌졸중환자 30명의남자와 6개월이상된 30명의남자뇌졸중환자를대상으로정상 50

4 Table 1. Longitudinal Studies on Poststroke Osteoporosis 37 Authors Subjects Site of DXA measurement Time from stroke to last measurement Paretic/nonparetic difference Lazoura 43 men, 24 women Fem. neck, troch., prox. rad., UD rad 12 months Fem. neck 13%, troch. 12.6% (12 months), prox. rad., UD rad. 7.34% (12 months) Hamdy 16 at start Total arm, total leg 6 months 6-month BMC: total arm 7.1%*, total leg 3.6%* Ramnemark Liu Jørgensen Yavuzer 13 men, 11 women 69 men, 35 women 21 men, 19 women 19 men, 13 women Total body, total arm, total leg 12 months 12-month BMC: total arm 22.9%*, total leg 6.8%* Total rad., humerus, UL, total femur, calcaneus, LL 203 days 203 days: total rad. 3.9%*, humerus 10.4%*, UL 7.5%*, total femur 5.8%*, calcaneus 1.2%*, LL 2.4%* Fem. neck, troch 12 months 12 months: fem. neck 4%*, troch. 4%* Lumbar spine, fem. neck, UD rad days 161 days: fem. neck 5%*, UD rad. 12%* DXA: Dual-energy X-ray absorptiometry, fem.: femoral, troch.: trochanter, prox.: proximal, rad.: radius, UD: ultradistal, UL: upper limb, LL: lower limb, BMC: bone mineral content. *: Difference found statistically significant by authors. 측과마비측의골밀도를비교하였고경직정도, 운동기능정도, 일상생활활동에따른비교를실시하였을때급성기뇌졸중환자에서마비측골밀도는정상측의골밀도와비교하여의미없었으며급성기와만성기의대퇴골평균골밀도는마비측과정상측모두에서의미가없었다. 그러나만성뇌졸중환자에서대퇴골의 ward 부위에서마비측의골밀도는정상측과비교하여의미있게낮았다. 골밀도와 Brunnstrom stage와경직정도, 일상생활동작정도와비교하여상관관계가없다고하였다. 다른연구에서뇌졸중후 1년간골밀도를주기적으로측정한결과골밀도는보행상태와연관성이있고 2개월이내에기립과보행을시작할경우골소실을줄일수있다고하였다. 35,36 추적연구는뇌졸중발생후골밀도와골량의변화를이해하는데중요하다. 하지만 12개월이상의장기간추적관찰된연구는거의없으며 Table 1에뇌졸중후골다공증의추적관찰데이터결과를정리하였다. 37 6) 뇌졸중후골다공증의치료뇌졸중후골다공증은여러요인의복잡한상호작용의결과일수있으며정확한평가가이루어져야하며가능한치료가필요하다. 가능한치료법으로 1 행동및재활치료 2 음식과비타민치료 3 약물치료로나눌수있다. 이번에는뇌졸중의골다공증에대한치료중약물치료위주로 Table 2에연구결과를정리하였다. 37 결론뇌졸중후골다공증환자의골다공증은폐경후골다공증과비교하여적절하게평가및진단되지못하여치료에적용되지않고있다. 골다공증의진단및치료에대한임상진료지침에도뇌졸중후골다공증이포함되어있지않다. 뇌졸중후골절은뇌졸중회복을저해하고병원입원기간을장기화하고있으며경제적인비용을늘리는요인이되고 51

5 Table 2. Poststroke Osteoporosis Treatments 37 Authors Type Subjects Treatment Treatment duration Time from stroke onset to treatment Results 29 women, 25 men 1α-OHD mg calcium 6 months 1,822 ± 2,155 days treatment group, 1,542 ± 1,628 days placebo group Vitamin D group had less BMD reduction and fewer hip fractures 280 men Risedronate 2.5 mg/day 18 months 90 ± 0.7 days treatment group, 90 ± 0.5 days placebo group Risedronate group showed fewer hip fractures and less BMD reduction 374 women Risedronate 2.5 mg/day 12 months 3 days treatment and placebo group Risedronate group showed fewer hip fractures and less BMD reduction 55 men, 53 women Etidronate 400 mg/day vs. placebo 56 weeks 7 ± 0 days in treatment and placebo groups Less BMD reduction in etidronate group 48 men, 60 women Menatetrenone 45 mg/day 12 months 13.2 ± 7.8 months treatment group, 13.9 ± 6.4 months placebo group BMD increased in menatetrenone group Ikai 81 women Etidronate 400 mg/day vs. 200 mg/day vs. no treatment 3 months 2.7 ± 1.4 months treatment group, 2.6 ± 1.2 months notreatment group Etidronate decreased BMD, reduction in high- ADL subgroup Poole 21 men, 6 women Zoledronate 4 mg/year 1 year < 35 days Zoledronate prevented BMD reduction Uebelhart 13 women, 21 men Calcitonin 200 IU/day 2 years 23 ± 11 days Tx group, 22 ± 8 days placebo Calcitonin did not influence bone metabolism markers DB: Double-blind, PC: placebo-controlled, : randomized-controlled trial, 1_-OHD 3: 1α-hydroxyvitamin D 3, ADL: activities of daily living 있다. 뇌졸중, 골다공증과골절은공통의위험인자이며주요위험인자즉고령, 골다공증, 자세조절을포함한위험인자의관리가필요하며골밀도측정을통한골다공증의적절한진단이중요하다. 비타민 D와골다공증치료약제의복용이뇌졸중후골절을예방하는데필요하다. REFERENCES 1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 2016;133: Hong KS, Bang OY, Kang DW, Yu KH, Bae HJ, Lee JS, Stroke statistics in Korea: part I. Epidemiology and 52

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R