J Korean Med Assoc 2013 December; 56(12): pissn: eissn: P

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1 pissn: eissn: Pharmacotherapeutics 백승훈 김신윤 * 경북대학교의학전문대학원정형외과학교실 Seung-Hoon Baek, MD Shin-Yoon Kim, MD* Department of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu, Korea *Corresponding author: Shin-Yoon Kim, syukim@knu.ac.kr Received October 1, 2013 Accepted October 15, 2013 variety of pharmacologic agents have been developed for the treatment of osteoarthritis. At A present, however, none of them has been proven to prevent disease progression, and the medications are used only for symptomatic relief. Thus, non-pharmacologic conservative treatment such as education, weight reduction in the obese, and consistent exercise should be recommended first to maintain fitness and tolerance to physical activity. Medication is then indicated to better control symptoms provided non-pharmacologic measures prove inadequate, and a successful strategy most likely would entail a combination of these non-pharmacologic and pharmacologic approaches. Acetaminophen can be tried first because of its efficacy and relatively safe profile, especially in those with mild osteoarthritis. Nonselective non-steroidal antiinflammatory drugs may be used in patients with moderate to severe pain, but long-term medication requires caution due to the increased risk of gastrointestinal and renal complications. Selective cyclooxygenase-2 inhibitors can be better tolerated, especially in patients with risk factors for gastrointestinal adverse events, but potential cardiac and cerebrovascular thrombotic events should be considered in those with preexisting cardiovascular disease. Tramadol and opioids are more potent analgesics. However, they are not recommended for routine use due to a high incidence of nausea, constipation, and drowsiness. These agents require close monitoring for those adverse effects, especially in a geriatric population. Lastly, the pharmacologic plan should be individualized according to the severity and duration of pain, age and gender of the patient, and concurrent comorbidities to maximize the benefit as well as to minimize the risk of adverse effects from medication. Keywords: Osteoarthritis; Pharmacologic treatment; Analgesics; Non-steroidal anti- inflammatory drugs; Disease-modifying osteoarthritis drugs 서 론 골관절염은임상적으로자주접하게되는흔한질환이다. 국민건강영양조사를토대로시행한국내연구에 의하면, 2010년현재 50세이상한국성인의 37.8%( 여성의 47.3%, 남성의 26.7%) 가슬관절의 Kellgren-Lawrence 2등급이상의방사선학적골관절염을보이고, 14.3%( 여성의 22.1%, 남성의5.3%) 에서방사선적이상과함께증상을동 c Korean Medical Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( 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. 대한의사협회지 1123

2 Baek SH Kim SY Mild pain Acetaminophen Selective COX-2 inhibitors nonselective NSAIDs (+gastro-protective agent*) Non-pharmacologic treatment Pharmacologic treatment Moderate/severe pain inflammation Selective COX-2 inhibitors nonselective NSAIDs (+gastro-protective agent*) As needed: tramadol, opioids, topical NSAIDs Surgical treatment Risk factors for GI adverse events Selective COX-2 inhibitors topical NSAIDs acetaminophen Nonselective NSAIDs +gastro-protective agent* asprin user (caution) Figure 1. Schematic approach for the treatment of osteoarthritis. *Gastro-protective agent: proton pump inhibitor (not prevent lower gastrointestinal [GI] complications), misoprostol, H2-receptor antagonist (high-dose famotidine only). COX, cyclooxygenase; NSAID, non-steroidal anti-inflammatory drug (From Korean Knee Society Subcommittee on Osteoarthritis Guidelines. J Korean Knee Soc 2010;22:69-74, with permission from Korean Knee Society) [6]. 반한슬관절의골관절염이환자인것으로보고되고있다 [1]. 이비율은연령에따라더욱증가하여 80세이상의성인 72.4% 에서슬관절의방사선학적골관절염이, 33.6% 에서증상을동반한슬관절의골관절염이환자인것으로추정되고있다 [2]. 골관절염은만성질환으로, 기대여명의증가와함께장기간의치료를요한다. 치료의선택은크게비약물적보존적치료, 약물요법및수술적치료로대분할수있고, 치료계획은증상의정도및기간, 방사선학적소견, 환자의나이및동반질환, 생활양식및사회경제적수준, 발병전활동도등에따라개별적으로수립되어야한다 [3,4]. 골관절염을적절하게관리하기위해서는교육, 과체중에서의체중감량, 적절한저충격유산소운동등의비약물적보존적치료가기본적으로실시되어야한다 [5]. 비약물적치료에효과가없거나, 질환이진행함에따라약물요법을고려할수있다. 그러나, 비약물적보존적치료는골관절염관리의근간이므로약물요법혹은수술적치료시에도이들요법은비약물적보존적치료와병행하여사용되어야한다. 수술적치료는약물적치료로는통증의적절한조절이되지않고, 기능이심각하게저하되어일상생활의제한이있으면서의학적금기 사항이없는경우적응증이된다 (Figure 1) [6,7] 1. 아세트아미노펜 경구용진통제로, 아세트아미노펜 (acetaminophen) 은비스테로이드항염제 (non-steroidal anti-inflammatory drugs, NSAIDs) 와유사한효능및상대적으로적은부작용과경제성으로경증의골관절염에서 1차약제로추천되고있으나 [8], 복용편의성및부작용을줄인선택적 NSAIDs (selective NSAIDs, cyclooxygenase [COX]-2 억제제 ) 의개발로최근에는약제의선호도가변화하는추세이다. 1) 작용기전골관절염에서의염증반응은유도성일산화질소합성효소의상향조절 (upregulation of inducible nitric oxide synthase) 및이로인한일산화질소 (NO) 의증가와관련이있는데, 아세트아미노펜은척추에서일산화질소및 substance P를억제하여작용하고, 최근에는 COX 억제효과가보고되고있다 [9]. 2) 효능메타분석 (meta-analysis) 에의하면아세트아미노펜은위약 (placebo) 대비휴식및활동기에통증을감소시키고, 유의한기능적호전을보인다 [10]. Cochrane review 역시아세트아미노펜이위약에비해유의한통증감소를보였으나, NSAID와비교시에는고관절및슬관절관절염에서약한통증조절효과가보고되었다 [11]. 3) 부작용권장량복용시부작용은드문것으로알려져있으나, 일일 2,600 mg 이상복용시소화불량, 구역, 복통및설사와같은위장관부작용이발생할수있다. 특히, 아세트아미노펜의오남용은드물지않으며, opioid-acetaminophen 복합체를함께처방하는경우과다복용될수있다. 미국식약청은 2009년아세트아미노펜제제가간손상을초래할수있는잠재적위험에대한경고를제품라벨에포함하도록결정하였으며, 전문가그룹의보고서에서과다복용을방지하기위한조처로일반의약품에서의사의처방이필요한전문 1124

3 약물요법 의약품으로전환할것, 성인 1회섭취량을현행 1,000 mg에서 650 mg으로줄일것, 하루최다섭취량기준을현행 4,000 mg에서 3,250 mg으로강화할것, 제품라벨에간부전등간의부작용을알리는강한경고문구를넣을것등을권고하였다. 신장기능저하로 NSAID 복용이곤란한경우, 비교적안전하게사용될수있는약물로인정된다. 아세트아미노펜은항응고제인와파린의반감기를증가시켜 prothrombin time을지연시킴으로출혈및응고장애가나타날수있으므로, 수술적치료가예정된환자에서는주의를요한다. 2. 비스테로이드항염제경구용 NSAID는골관절염치료에서가장흔히쓰이는약제로, 골관절염의중등도혹은중증의통증조절에흔히사용되며, 국내에서도 100여종이상이다양한상품명으로시판되고있다. 1) 작용기전 NSAID는 COX와 leukotriene의기능을저해하여, arachidonic acid가 prostaglandin으로전환되는것을억제한다. COX에는 2종류의동위효소 (isoenzyme) 가있으며, COX-1은대부분의조직에서항시발현되는반면, COX-2는염증반응에의해유도된다. 따라서, NSAID와관련된진통효과는 COX-2 억제에기인하는반면, COX-1은혈소판응집, 위점막보호, 신장에서의혈류조절등과관련이있어, COX-1 억제시상부위장관출혈및궤양등의심각한부작용을야기할수있다. NSAID는이외에도일산화질소및 superoxide free radical 합성억제를통한항염증작용이보고되고있다. 골관절염의진행은활막의염증, cytokine 증가, 단백분해등으로인한연골파괴를필연적으로수반한다 [12-14]. NSAID는전신및국소활막에서의염증반응은감소시키는것으로알려져있으나, 상기의진행과정을호전시킨다는근거는부족한실정으로, 동물실험에서는오히려 COX-1 억제시 proteoglycan 생성저하를통한골관절염의악화가보고되고있다 [15]. 2) 효능 NSAID는그성상에따라 propionic acid 유도체 (ibuprofen, naproxen, ketoprofen, pelubiprofen 등 ), acetic acid 유도체 (indomethacin, aceclofenac, diclofenac 등 ), enolic acid 유도체 (piroxicam, meloxicam 등 ), fenamates 및 COX-2 억제제 (celecoxib) 등으로분류할수있다. 그러나, 약제의다양한종류에도불구하고, 관절염에서통증이완화되는효능은비슷하여, 복용편의성및적은상부위장관부작용을가진약제가선호되고있다. 3) 부작용메타분석에의하면비선택적 NSAID는아세트아미노펜에비해위장관합병증의위험도가 35% (95% confidence interval [CI], ) 증가되어있으며 [16], 미란, 궤양, 천공및출혈을야기할수있다. 상부위장관출혈의위험인자로는 65세이상의고령, 위장관출혈이나위궤양의과거력, 스테로이드나항응고제의병용, 동반질환, 흡연및음주등이있다. 특히관절염이빈발하는 65세이상의고령의환자에서는위궤양으로인한입원혹은사망의 20-30% 가 NSAID 의사용과연관이있다고보고되므로주의를요한다 [17]. NSAID는신장에서혈류및사구체여과율, 수분재흡수등을조절하는 prostaglandin I2 (prostacyclin) 를감소시키며, 장기간사용시신부전, 수분저류, 고칼륨혈증, 혈압상승등을초래할수있으므로, 경증의신기능저하가있는환자에서도주의를요한다. 위험인자로는이뇨제병용으로인한체액량감소, 신장질환의과거력, 간질환등이있다. NSAID는혈소판응집을저해하여위장관출혈을악화시킬수있으나, 아스피린과는달리가역적으로작용한다. 또한아스피린과민성이있는환자에서는 NSAID는금기이다. 부작용의종류는약제마다다양한차이를보인다. Ibuprofen의경우 1,600 mg 이하의용량에서위장관부작용은상대적으로적은반면, sulindac이나 nabumetone의경우상대적으로신독성과혈소판에대한부작용이적은것으로알려져있고, diclofenac은경도의담즙저류를야기할수있다. 4) 선택적비스테로이드항염제 COX-2 억제제는 COX-1보다 COX-2에최소 배의선택성을가진다. 따라서, COX-1에의해매개되는혈소판응집이나출혈시간에는유의한영향을미치지않으므로, 대한의사협회지 1125

4 Baek SH Kim SY 이론적으로는 COX-2억제제는위약에필적하는적은위장관부작용을가지면서, 비선택적 NSAID에상응하는진통효과를가지게된다. 반면, COX-2를억제함으로써신혈류와심혈관확장을조절하는 prostacyclin의생성을저하시켜, 신독성이나심혈전증을악화시킬가능성이있다. 실제 rofecoxib와 valdecoxib는과도한빈도의심근경색증발생으로각각 2004년과 2005년퇴출되었다. 이는 COX-1의혈소판응집효과는영향을받지않으면서, COX-2에의한 prostacyclin 생성이저하되는불균형으로인한것으로추정되고있다 [18]. 그러나, 심혈관계위험에대한 COX-2 억제제와전통적인비선택적 NSAID의비교연구는부족한실정으로, 비선택적제제역시 COX-2 선택적제제보다는낮지만심혈관계위험을증가시킬가능성은있다. 따라서, 심혈관계위험요인이있는환자에서는비선택적 NSAID나 COX-2 선택적억제제의사용은모두심혈관계위험성을증가시킬수있으므로주의를요한다 [6]. 5) 국소비스테로이드항염제국소 NSAIDs (topical NSAIDs) 는경구용제제와비슷한효능을가지면서, 피부흡수를통해위장관부작용및신독성을감소시키고자 gel이나 patch의형태로제조되고있다. 그러나피부를통과하여혈류에흡수되나직접연골이있는심부조직까지투과할수는없다. 경구용제제의보조제혹은경구용제제로인한부작용이예상되는고령의환자들에게안전한대체제로사용될수있으나, 피부건조및발적이흔한합병증으로보고되고있다 [19]. 6) 비스테로이드항염제처방의실제비선택적 NSAID 복용시위장관합병증의예방을위해 misoprostol, proton pump 억제제혹은고용량의히스타민수용체길항제 (H2-receptor antagonists) 를병용할수있다 [20]. NSAID를복용중인 8,843명을대상으로한무작위이중맹검대조군연구에서 misoprostol 200 μg을하루 4번병용하였을때, 위약군에비해위궤양의위험도를 51% 감소시켰고, 위천공, 위출구폐쇄혹은출혈과같은중대한합병증도감소시킬수있는것으로보고되고있다. 위궤양예방은고용량의 misoprostol에서더욱효과적으로알려져있으나, 용량증가에따라설사및복부팽만증의빈도도증 가하므로주의를요한다 [21]. Proton pump 억제제와고용량의히스타민수용체길항제의경우 misoprostol에비해설사등의부작용은상대적으로적은것으로알려져있으나, proton pump 억제제는하부위장관합병증예방에는도움이되지않고, 히스타민수용체길항제는위궤양예방에는효과가적다 [20]. 위장관합병증은 NSAID의용량에비례하므로, 저용량에서시작하되 2-4주사용후에도통증이적절히조절되지않는경우용량증가혹은다른약제로의전환을고려한다. 통증의급성악화를조절하기위한목적으로가급적단기간으로사용하되, 2종류이상의 NSAID의혼용시진통효과증가는명확하지않은반면, 부작용은증가할수있으므로, 심부전및뇌졸증예방을위해아스피린 ( mg/day) 을복용하는경우외에는혼용을피하는것이좋다 [8]. 그러나, 저용량의아스피린을병용하는경우에도상부위장관의출혈위험도는증가하므로비선택적 NSAID보다는 COX-2 억제제의사용이권장되며, 이경우항궤양제의추가적인투여가필요할수있으므로주의를요한다. 또한, 위장관출혈의과거력이있는고위험군역시, 선택적 COX-2 억제제복용후에도출혈의재발이약 9% 정도보고되고있으며, 이경우에도 proton pump 억제제와병용투여시재발을예방할수있는것으로보고되고있다 [22]. COX-2 억제제는 ibuprofen이나 diclofenac에비해고혈압의병발률은낮은것으로보고되고있으나 ( 각각 1.7% 및 2.3%/yr) [23], 신독성및승압작용은비슷한빈도를보인다. 따라서, COX-2 선택성여부에관계없이 NSAID 장기사용시에는정기적인신장기능검사와요및혈액검사, 혈압과부종에대한평가가필요하다 [24]. 반감기의 3배가지나면혈소판기능이정상화되므로수술이예정된경우, NSAID 반감기의최소 5배의기간전에중지하는것이바람직하며, 약제중단시에는점진적으로감량하도록한다. 국제골관절염학회 (Osteoarthritis Research Society International) 의 2010년치료지침에서는아세트아미노펜이 1차약제로권고되고있으며, 2차약제는위험-효용도를평가하여, 심질환의위험도가없는경우위장관부작용의예 1126

5 약물요법 방에따른비용-효용성으로 COX-2억제제를 2차약제로권고하고있다 [25]. 미국류마티스학회 (American College of Rheumatology) 의 2000년지침에서는 COX-2 억제제는아미노아세트펜으로통증이조절되지않는환자, 특히위장관합병증의위험인자를가지는환자에서 2차약제로권고되고있다 [8]. 따라서, COX-2 선택성여부는위장관합병증및심근경색의위험도를고려해서신중히선택해야할것이다. 3. Opioid Opioid는아세트아미노펜과 NSAID 사용이금기이거나반응이적은경우혹은수술적치료가필요한중등도혹은중증의관절염에서수술적치료를거부하거나곤란한경우, 사용이제안되고있다 [6,8]. Tramadol은약한합성아편양작용제 (weak synthetic opioid agonist) 로 norepinephrine과 serotonin의재흡수를저해하여, ibuprofen이나 diclofenac과비슷한진통효과를가지며 [26], 매 6시간마다 mg을복용하는것이효과적인것으로알려져있다 [8]. 메타분석에의하면 tramadol 처방군은위약군에비해중등도이상의통증감소가약 37% (95% CI, 20-50%) 정도많은것으로보고되고있으나 [27], 구역, 변비및기면 (drowsiness) 등의부작용과장기사용시의존성이발생할가능성이있으므로주의를요한다 [28]. 또한발작에대한역치를감소시키므로간질환자에서는금기이다 [8]. 강한마약성진통제 (strong opioids) 는다른약물에효과가없는매우심한골관절염통증치료에고려될수있으나의존성및남용우려가있어매우선별적인사용이권고된다 [6]. 3,244명의관절염환자를분석한메타분석에서는 13-18주투여후통증호전에상당한효과가있고, 유의한기능의호전도관찰되었다고기술하고있다 [29]. 그러나, 위약군 (7%) 대비높은탈락률 (25%) 을보고하고있어, 마약성진통제의효능을부작용이상쇄하는단점이있다. 약물중단은 oxymorphone, oxycodone, oxytrex, fentanyl 및 morphine sulphate 등강한마약성진통제 (31%) 에서 tramadol, codeine 및 propoxyphene 등의약한마약성진통제 (19%) 보다높게관찰되었고, 부작용은구역 (30%), 변비 (23%), 기면 (20%), 졸림 (18%), 구토 (13%) 의순이었다. 따라서, 사용시저용량에서시작하되의존성혹은중독에대한감시가필요하며, 고령의환자에서는낙상의위험이증가하여골다공증성골절이발생할수있으므로주의를요한다 [30]. 최근에는고령의환자들에서신장과간에영향이적고, 편의성을높인 patch제제가소개되고있다. 4. Topical capsaicin Capsaicin은피부작열감을야기하여 unmyelinated nociceptive C fiber에서 substance P를제거함으로써, 통증전달을억제혹은조절하는역할을하는것으로추정되고있다. 70명의골관절염과 31명의류마티스관절염환자를대상으로한무작위이중맹검대조군연구에서일일 4회 0.025% topical capsaicin군에서위약군 (33%) 대비유의한진통효과 (57%) 를보였으며 [11], 일일 2회 0.075% capsaicin 역시효과가있는것으로알려져있다. 증등도이하의골관절염에서경구진통제혹은소염제와함께사용될수있는보조치료혹은대체요법으로서고려할수있으나 [6], 도포부위에종종나타나는심한작열감은단점으로지적되고있다. 5. 관절내주사 1) Hyaluronic acid 정상관절의점탄성은 hyaluronic acid에의해유지되는데, 골관절염에서는염증반응에서발현되는분해효소들에의해 hyaluronic acid의분해가촉진되어활액의점탄성이감소하게된다 [31]. 따라서, 관절강내 hyaluronic acid 주사를점성보충 (viscosupplementation) 이라고명명하기도한다 [32]. 효능이활막내반감기보다오래지속되므로정확한약리기전은알수없으나, cytokine이나 prostaglandin과같은염증매개체의억제, 연골기질의생성촉진및분해저하, 통증수용체의감작등으로추정되고있다 [8]. 중등도이하의골관절염환자중 NSAID 사용이금기이거나효과가부족한경우사용을고려할수있다 [18]. 진통효과는시간이지나면서감소하여 14주를넘지않는것으로알려져있다. 효능에대해서는최소 17편이상의 systemic 대한의사협회지 1127

6 Baek SH Kim SY review가존재할만큼많은연구가시행되었다. 가장광범위한연구는 2006년의 Cochrane review라할수있으며, 총 76편의연구들을분석한결과최초 4주내에유의한진통효과 (effect size, ES=0.60) 및기능개선 (ES=0.61) 효과가있다고보고하였다 [33,34]. 그러나, 국제골관절염학회의 2010년권고에서는상기 review는연구자간결과의편차가크고 (considerable heterogeneity of outcomes), Egger test로분석시투고잡지에따른출판편향성 (publication bias) 이있다고기술하면서, Jadad score 5를가지는양질의무작위대조군연구에한해분석을시행하면, 유의한진통효과를관찰할수없다고기술하여본제제의진통효과에대해서는아직논란의여지가있는실정이다 [25]. Hyaluronic acid는비교적부작용이적은약물로알려져있으나, 가성화농성관절염 (pseudoseptic arthritis) 이생길수있고, 주사술기와관련하여화농성관절염이합병될수있으므로주의를요한다. 분자량차이에따른진통효과의차이에는논란이있으나, 고분자량의 hyaluronic acid에서는통증의일시적악화및부종이상대적으로호발하는것으로보고되고있다 [35]. 2) Corticosteroid 삼출이나국소염증증상을보이면서중등도이상의통증이있는골관절염환자에서, 단기적인증상완화의목적으로관절내주사를고려할수있다 [6]. 감염등의다른원인이배제된상황에서관절염통증의급성악화시일시적인증상의호전을얻을수있으나, 반복적인관절내투여는연골손상을악화시킬수있으므로, 최소 3-6개월의간격을두고주사할것이추천된다 [36]. 투여 24시간내에일과성의발적및통증이발생할수있으나대개 48시간이내에호전되는양상을보인다. 역시주사술기와관련하여감염에주의한다 [37]. 3) 약제의선택최근관절내 hyaluronic acid와 corticosteroid 주사를비교한무작위대조군연구 7편을분석한메타분석에서는주사 2주째진통효과는 corticosteroid가더우수했으나, 4주째에는차이가없고, 8주째에는 hyaluronic acid가우수하며, 진통효과의차이는 12주및 26주째에유의하였다고 보고하였다 [38]. 따라서삼출등을보이는골관절염의급성악화시에는 corticosteroid를, 골관절염의만성통증에는 hyaluronic acid의투여를고려하는것이바람직할것이다. 6. SYSADOA 혹은 DMOAD SYSADOA (symptomatic slow-acting drugs for osteoarthritis) 는골관절염에서기존약물에비해효과가서서히나타나면서진통등의증상호전의효과가있는약물을통칭하며, 연골파괴를연기혹은예방하여초기골관절염의경과에긍정적인영향을기대할때 DMOAD (disease-modifying osteoarthritis drugs) 혹은구조개선골관절염치료제 (STMOAD, structure-modifying osteoarthritis drug) 라명명하나, 골관절염의진행을차단하는확실한방법은아직까지없다. 또한연구용자기공명영상을이용하더라도연골재생에대한평가는대단히어려워치료효과를증명하기곤란하고, 일부연구에서확인된방사선학적관절간격감소효과와임상적의미와의상관관계도입증이부족한실정이다. 이러한범주에는 glucosamine sulphate, chondroitin sulphate, diacerhein, avocado soybean unsponifiables, hyaluronan 등이있다. 1) Glucosamine Glucosamine은연골에서세포외기질을구성하는글리코사미노글리칸 (glycosamninoglycan) 의전구체이다. 증상호전에대한연구로, 2005년 Cochrane review에서는중등도의호전 (ES=0.61) 을보고하였고, 2007년국제골관절염학회에서는이를근거로증상이있는슬관절염환자에서효용이있을수있다고기술한바있다 [39]. 그러나, 현재까지출판된증상호전에관한 20여편의무작위대조군연구들을분석하면 glucosamine hydrochloride에서는유의한증상호전이관찰되지않았고, glucosamine sulphate의경우중등도의진통효과 (ES=0.58) 가관찰되나, 연구자간의결과의편차가크고 (I2=87%, P<0.0001), 투고잡지에따른출판편향성 (P=0.009) 을보이고있다 [25]. 더욱이 Jadad score 5를가지는양질의무작위연구 7편에한해분석을시행할때, 출판편향성은없으나 (P=0.074), 연구자간결과의편차 (I 2 =84%, P <0.0001) 는여전히존재하고, 진통효과 1128

7 약물요법 (ES=0.29) 는감소한결과를보이며, 최근연구일수록그효과는더욱감소하는경향을보였다 [25]. 2007년 15편의무작위대조군연구들을분석한 systemic review에서는할당은닉 (allocation concealment) 이적절하지않았던연구에서는 glucosamine sulphate의효용이있었으나 (ES=0.42), 그렇지않은연구에서는증상호전이없었고, 기업체의후원을받는연구 (ES=0.44) 에비해후원이없었던연구는그효과가없었다고보고하고있다 [40]. 또한 CONSORT (consolidated standards for reporting clinical trial) statement를충족하는 1998년이후의무작위대조군연구만분석하였을때연구결과간의편차는적고 (I 2 =0%), 출판편향성도없으나, glucosamine sulphate의진통효과 (ES=0.13) 는감소함을보고하고있다 [25]. 구조개선효과 (structure-modifying effect) 역시논란의여지가있다. Glucosamine sulphate 단독제제를사용한 3편의무작위대조군연구들 (gluconate sulphate 1,500 mg/day) 를분석하면, 내측구획의관절간격이감소한슬관절관절염에서는적은효과 (ES=0.24) 가있는것으로보고하고있으나, 3년간복용후에도위약군과의차이가 0.23 및 0.25 mm로극히미미한점에주의하여야한다 [41,42]. 고관절관절염에서는 2년복용후에도구조개선효과가입증되지않았다 [43]. 또한최소 1년간 gluconate sulphate (1,500 mg/day) 를복용한슬관절염환자들을대상으로한무작위대조군연구에서 5년내슬관절인공관절치환술의빈도가위약군 (14.5%) 에비해유의하게감소 (6.3%) 하였음을보고하였다 [44]. 그러나인공관절치환술시술의결정인자로는방사선학적악화외에도통증의정도, 나이와성별, 동반질환, 의사및환자의주관적선호도등다양한요인이작용할수있으므로, 해석에주의를요한다 [45]. 2) Chondroitin sulfate Chondroitin은세포외기질을구성하는중요한 glycosaminoglycan의하나로, 정확한작용기전은아직밝혀져있지않다. 메타분석에서 chondroitin 단독으로는슬관절혹은고관절골관절염에효과가없고, glucosamine 복합제에서효과가있는것으로보고되어 [46] 흔히 glucosamine과함께복합체의형태로시판되고있다. 최근메타분석에서는 비교적큰진통효과 (ES=0.75) 가보고되고있으나 [46], 역시출판편향성이크고, 연구자간결과의편차가심하며 (I2=92%), 최근연구일수록효능이감소하는경향을보인다 [25]. 또한 Jadad score 5를가지는양질의무작위대조군연구들에한해분석을시행하면, 진통효과가없는것으로보고되고있다. Chondroitin sulfate의구조개선효과에관한 systemic review에서는위약군에비해유의한관절간격감소억제효과를보고하고있으나 [47], 그정도역시미미하고 (0.07 mm/yr), 분석에포함된무작위대조군연구들모두가기업후원하에시행되어해석에주의를요한다. 결 론 골관절염은만성질환으로, 기대여명의증가와함께장기간의치료를요한다. 골관절염의진행을차단하는확실한방법은아직까지없으며, 비약물적보존적치료가약물요법에선행하여야한다. 대부분의약물요법의목표는증상호전에있으며, 약물의종류는증상의정도및기간, 동반질환및복용중인다른약제와의상호작용등을고려하여개별적으로신중히선택하여야한다. 환자및의사는현실적인목표를가지고치료에임해야하며, 무엇보다비약물적보존적치료는골관절염관리의근간이므로약물요법시에도비약물적보존적치료와병행하여야한다. 핵심용어 : 골관절염 ; 약물요법 ; 진통제 ; 비스테로이드항염제 ; 경과조절골관절염약제 REFERENCES 1. Shin DW, Nam S, Bang YS, Lee JY. Estimation of the prevalence of Korean adults aged 50 years or more with knee osteoarthritis based on the data from fifth Korea National Health and Nutrition Examination Survey. J Korean Med Assoc 2013;56: Baek GH. Are we prepared for geriatric orthopedics? Clin Orthop Surg 2010;2: Lee SC, Jung KA, Nam CH, Jung SH, Hwang SH. The shortterm follow-up results of open wedge high tibial osteotomy with using an Aescula open wedge plate and an allogenic bone graft: the minimum 1-year follow-up results. Clin Orthop Surg 2010;2: 대한의사협회지 1129

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