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1 대한한의학회지제 41 권제 1 호 (2020 년 3 월 ) J Korean Med. 2020;41(1):55-83 pissn eissn Original Article 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 이연재 1, 조효림 2, 김선혜 2, 성원석 2, 김은정 2* 1 동국대학교한의과대학, 2 동국대학교분당한방병원침구의학과 Efficacy and Safety of Pharmacopuncture and Bee venom Acupuncture for Knee Osteoarthritis: A systematic review and meta-analysis Yeon Jae Lee 1, Hyo Rim Jo 2, Seon Hye Kim 2, Won Suk Sung 2, Eun Jung Kim 2* 1 College of Korean Medicine, Dongguk University 2 Dep. of Acupuncture & Moxibustion Medicine, Dongguk University Bundang Oriental Hospital Objectives: The purpose of this study was to evaluate the efficacy and safety of pharmacopuncture and bee venom acupuncture for knee osteoarthritis. Methods: We searched for randomized controlled trials that investigated the effects of pharmacopuncture and bee venom acupuncture on knee osteoarthritis through the electronic databases including Pubmed, EMBASE, Cochrane, CiNii, CNKI, KMBASE, KISS, NDSL, and OASIS. Meta-analysis was performed by Review Manager software and the quality of included studies were assessed by the Cochrane risk of bias tool. Results: A total of 20 articles with 1536 participants were identified. 12 trials about phamacopuncture and 8 trials about bee venom acupuncture showed significant improvement than sham treatment, western medicine treatment, and other Korean medicine treatment such as acupuncture in diverse scales. Six trials reported adverse events. Conclusions: These findings showed certain efficacy and safety of pharmacopuncture and bee venom acupuncture. It would be helpful for patients and Korean medicine doctors in the choice of the treatment for knee osteoarthritis. Well-designed studies with long term follow up and more number of participants should be conducted to strengthen the evidence of the use of pharmacopuncture and bee venom acupuncture. Key Words : Knee osteoarthritis (knee OA), Pharmacopuncture, Bee venom Acupuncture, Systematic review, Meta-analysis 서론슬관절은인체에서가장큰윤활관절로가동성은높지만상대적으로불안정한구조로이루어져있고체중의부하를직접적으로받는것이특징이다. 1,2) 지 속적인상하의압력에노출되어퇴행성변화가많이일어나는가운데이로인한퇴행성슬관절염 (knee osteoarthritis, knee OA) 는연골과연골하부의국소적인퇴행성변형뿐아니라, 연부조직및관절주위에도조직학적변화를나타내며임상적으로는반 Received:13 February 2020 Revised:27 February 2020 Accepted:27 February 2020 Correspondence to:eun Jung Kim Department of Acupuncture & Moxibustion Medicine, Dongguk University Bundang Oriental Hospital 268, Buljeong-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13601, Republic of Korea Tel: , Fax: , hanijjung@naver.com 55

2 ( 56 ) Journal of Korean Medicine 2020;41(1) 복적인통증, 부종, 근육의단축과경직감을유발한다 3). 이러한 knee OA의보존적치료로주사, 약물, 운동, 물리치료등이있다. 이중스테로이드주사는빠른진통효과는있지만장시간노출시연골손상가능성이있고 4), 비스테로이드항염증제 (non-steroidal anti-inflammatory drugs, NSAIDs) 와같은약물치료는심혈관및위장관장애의부작용발생가능성이라는단점이있다 5,6). 이러한가운데침, 화침, 매선요법과같은한의학적치료를시도한사례가있었고, 그형태는증례보고 (case report), 무작위배정비교임상시험 (randomized controlled trial, RCT), 체계적문헌고찰 (systematic review, SR) 등다양하다 7-10). 한의학적치료중약침및봉독요법은정제된한약제제를환부및질병과관련된경혈점에주입함으로써침이갖는물리적자극뿐아니라약물의화학적효과를동시에갖는치료방법이다 11). Knee OA에대한효과로골관절염의진행억제, 연골변형및염증억제의효과및봉독의유의한진통능력을보고한실험연구 12) 와침치료보다우월한효과를보고한임상연구등이있다 13). 하지만, 약침및봉독요법에대한 SR의경우통증, 외상성손상, 족관절염좌를주제로한보고는있으나 14-16), knee OA에대한고찰은부족한실정이다. 이에본연구에서는 SR을통해약침및봉독요법이 knee OA에얼마나효과적이고안전한가를객관적으로평가하고자하였다. 대상및방법 1. 논문검색 2019년 8월 2일까지국내외에게재된논문들을대상으로 Pubmed, EMBASE, Cochrane library, CiNii, CNKI 5개의국외데이터베이스와 KMBASE, KISS, NDSL, OASIS 4개의국내데이터베이스를활용하였 다. 질환검색어설정의경우, 국외논문검색어는 osteoarthritis, knee, degenerative arthritis, deformans, knee, randomized controlled trial 위주로검색하였고, CNKI의경우 性関節炎, 骨関節炎, 関節炎, 骨関節病, 退行性, 膝关节骨性关节炎, 退行性关节炎, 骨关节炎, 随机, 对照 을조합하여추가로검색하였다. 국내논문검색어의경우 슬관절염, 무릎골관절염, 퇴행성관절염, 무릎 을조합하여검색하였다. 중재치료검색어는각국내외데이터베이스에서 pharmacopuncture, aquacupuncture, acupoint injection, hydro acupuncture, bee, bee venom, apitherapy, 薬鍼, 水针, 蜂鍼, 약침, 봉침, 봉독 을조합하여검색하였다. 2. 선정기준연구선정은 knee OA 환자를모집하여 RCT를시행한연구를 1차대상으로하였다. 연구형태가 SR, 메타분석및 non-rct, case report, 환자대조군연구 (case-control study), 연속증례군보고 (case series), 문헌고찰 (article review), 프로토콜논문 (study protocol), 동물실험등의연구는제외하였다. 발행국가의제한은없었고언어는한국어, 영어, 중국어, 일본어로제한하였다. 중재치료는약침및봉독요법을시험군으로설정하되, 대조군을무처치, 거짓치료 (sham), 한방치료및 ( 통상적 ) 양방치료로설정한연구를포함하였다. 한, 양방치료를각군에서동일하게시행한경우병행치료로인정하여포함시켰으나그렇지않은경우제외하였고 ( 예 ) 약침 + 뜸 vs. 침 ), 기타약침및봉독요법의횟수, 기간, 자입한혈자리에따른연구, 한의사들이일반적으로시행하지않는약침제제를이용한경우 ( 예 : 비타민약침 ) 도제외하였다. 연구대상자의경우성별, 연령, 인종, 유병기간에는제한을두진않았으나슬관절수술후관리, 정신질환, 심혈관계, 뇌혈관계, 간장, 신장, 혈액학적질환 56

3 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 57 ) 이있는경우제외하였다. 3. 연구선택두명의연구자 (KSH, JHR) 이독립적으로논문을검색, 1차로제목과초록을통해본연구와무관한논문을배제하였고, 이후통과한연구는전문을확인하여 2차로적합성을확인하였다. 독립된두연구자사이의평가가불일치할경우, 제 3 연구자 (KEJ) 의자문을통해최종선별하였다. 4. 데이터추출및효과분석최종선정된연구에서미리정해진자료추출서식에따라두명의연구자 (KSH, JHR) 이독립적으로자료를추출하였다. 추출서식에는발행연도및국가, 표본크기, 중재방법및기간, 평가지표및결과, 안전성이포함되었고안전성의경우, 군에상관없이보고된이상사례를모두검토하였다. 연구자간의이견이있는경우제 3 연구자 (KEJ) 와의토의를거쳐진행하였다. 한편메타분석의경우 Review Manager software (version 5.3; Copenhagen; The Nordic Cochrane Center, The Cochrane Collaboration, 2014) 을사용하였고, 분석가능한평가지표가없거나연구간의이질성이높아통계적인합성을할수없다고판단되는논문은제외하였다. 5. 비뚤림위험평가 (Risk of bias) 선정논문의비뚤림위험평가를위해서두명의연구자 (KSH, JHR) 이최종선정된 17편의논문에대해 Cochrane Collaboration의 risk of bias (RoB) tool을이용하여독립적으로평가하였다 17). 무작위배정순서의생성, 배정순서의은폐, 연구참여자및연구자에대한눈가림, 결과평가에대한눈가림, 불완전한결과자료, 선택적보고, 기타비뚤림위험의 7가지문항에대해문헌의내용에따라비뚤림위험높음 (high risk), 낮음 (low risk), 불확실함 (unclear) 으로구분하였다. 두연구자사이의평가가 불일치할경우, 제 3 연구자 (KEJ) 자문을통해재평가하여결론을도출하였다. 결과 1. 연구문헌선정결과 9개의데이터베이스에서총 903편 (Pubmed 317 편, EMBASE 32편, Cochrane 35편, CNKI 62편, KMBASE 26편, KISS 183편, NDSL 210편, OASIS 38편 ) 이검색되었다. 데이터베이스를제외한다른방법을통해검색된논문은 1편으로중복논문 73개가제외되어, 총 831개의논문을대상으로 screening을시행하였다. 그결과, 선정기준상대상질환 (knee OA) 이아니거나연구대상 ( 인간 ), 중재 ( 약침및봉독요법 ) 및연구형태 (RCT) 에부합하지않는연구 780개가제외되어 51개의논문이 1차선정되었다. 이후본문고찰을통한 eligibility를확인한결과, 본문미확보 (2편), 시험중재의기준에해당하지않거나 (14편), 선정기준에부합하지않는연구형태를보인논문 (15편) 등총 31편이제외되었다. 그결과 20편의논문이선정되었으며, 이중분석가능한평가지표가없거나평균, 표준편차가기술되어있지않는등통계적인합성이어려운 4편 19,20,35,36) 을제외한총 16편을대상으로메타분석을시행하였다 (Figure 1). 2. 자료추출및분석최종선정된 20편의논문은아래와같이분석되었다 (Table 1, 2). 1) 발행국가및연도 20편의논문은중국 12편, 한국 7편, 미국 1편순으로중국에서가장많이발행되었다. 모두 2001년이후에게재되었으며, 2001년, 2002년, 2003년, 2004 년, 2009년, 2010년, 2011년, 2016년, 2018년, 2019 년에각 1편씩게재되었고, 2006년, 2013년, 2015년 57

4 ( 58 ) Journal of Korean Medicine 2020;41(1) Fig. 1. Flow chart of the trial selection process 에는각각 2 편, 2014 년에는 4 편이게재되었다. 2) 표본의크기분석 20 편논문에등록된연구참여자수는 1536 명으 로, 중재군이 809명, 대조군이 727명이었다. 50~100 명의환자를대상으로한연구가연구 17편으로가장많았고, 50명미만은 2편, 100명초과는 1편이었고, 모두성별및나이에제한을두지않았다. 58

5 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 59 ) Table 1. A Characteristics of the Included Studies No. Study Year Country 1 Shin ) Korea Study Size 40 E: PA (20) Intervention (n) C: Placebo (20) 2 Kim ) Korea 53 E: PA (29) C: Placebo (24) 3 Park ) Korea 4 Yu ) China 5 Sun ) China 60 E: PA (30) 60 E: PA (30) 58 E: PA (20) C: AC (30) C: IA (30) C1: AC (20) C2: Medicine (18) 6 Cai ) China 7 Hua ) China 8 Gao ) China 60 E: PA+IA (30) 60 E: PA+IV (30) 80 E: PA+IA +Medicine (40) C: IA (30) C: IV (30) C: IA +Medicine (40) Outcomes Results 1. SF-MPQ 1) VAS 2) PPI 3) sensory 4) affective 2. WOMAC 3. EQ-5D 1. VAS 2. WOMAC 3. KHAQ 4. SF ) E>C (p=0.000) 2) E>C (p=0.049) 3) E>C (p=0.004) 4) E=C 2. E>C (p=0.004) 3. E>C (p=0.020) 1. E=C 2. E=C 3. E=C 4. E=C 1. Lysholm score 2. Nine point scale 1. Effective rate 2. Intra bony pressure 1. E=C 2. E>C (Statistics not mentioned) 1. E>C (p<0.05) 2. E>C (p<0.05) 1. Effective rate 2. ISOA 3. Serum NO levels 1. VAS 2. Lysholm score 3. Effective rate 1. VAS 2. WOMAC 1. E>C1 (p=0.005) E>C2 (p=0.031) 2. E=C1=C2 (Statistics not mentioned) 3. E=C1=C2 (Statistics not mentioned) 1. E>C (p<0.01) 2. E>C (p<0.05) 3. E>C (p<0.05) 1. E>C (p<0.05) 2. E>C (p<0.05) 1. VAS 2. WOMAC 3. Lequesne scale 4. Inflammatory cells and CRP levels in synovial fluid 1. E>C (p<0.05) 2. E>C (p<0.05) 3. E>C (p<0.05) 4. E>C (p<0.05) Adverse event (n) Author's conclusion NR PA therapy can be an effective treatment in knee OA E: Nausea (1), itching (1) C: Dizziness (1) Although, the experimental group was effective in VAS at 7th treatments, but there was no significant difference between two groups. NR PA was not more effective than Filiform acupuncture statistically. NR PA can significantly improve symptoms and sign of knee OA NR PA in treating knee OA is safe and effective, the course of treatment no side effects. NR PA+IA is an effective method in treating knee OA NR PA+IV can be applicable to improve symptoms. E : itching (2), rash (2) C : itching (2), rash (1) PA+IA improve knee joint function, suppress local inflammatory response. worthy of clinical application 59

6 ( 60 ) Journal of Korean Medicine 2020;41(1) Table 1. A Characteristics of the Included Studies No. Study Year Country 9 Ye ) China Study Size 90 E: PA+WN (30) Intervention (n) C1: Medicine (30) C2: WN (30) 10 Zhang ) China 60 E: PA+AC (30) C: AC (30) 11 Liu ) China 12 Li ) China 13 Conrad ) USA 60 E: PA+EA (30) C: EA (30) 100 E: PA+HM (50) C: HM (50) 367 E: BV (234) C: Placebo (133) 14 Lee ) Korea 50 E: BV (25) C: AC (25) 15 Ryu ) Korea 51 E: BV (26) C: AC (25) 16 An ) Korea 30 E: BV (17) C: AC (13) Outcomes Results Adverse event (n) Author's conclusion 1. Effective rate 1. E>C1, C2 (p=0.000) NR PA+WN has more significantly clinical effect in treating Knee OA 1. VAS 2. WOMAC 3. Knee circumstance score 1. VAS 2. Lysholm score 3. Effective rate 1. E>C (p=0.043) 2. E>C (p=0.045) 3. E>C (p=0.026) 1. E>C (p<0.01) 2. E>C (p<0.01) 3. E>C (p<0.05) E: Bruise (3) C: Bruise (3) PA+AC has shown in terms of overall improvement in symptoms NR PA+EA is more effective better than EA only. 1. Effective rate 1. E>C (p<0.05) NR PA is effective in treating knee osteoarthritis 1. WOMAC 1) pain 2) fuction 2. VAS 3. PGA, PhGA 1. Effective rate 2. Nine-point scale 3. Grade of clinical symptoms 1. VAS 2. WOMAC 1) total 2) pain 3) stiffness 4) function 3. Lequesne's index 1. 1) E>C (p=0.001) 2) E>C (p=0.0046) 2. E>C (p<=0.0012) 3. E>C (p=0.0015) 1. E>C (Statistics not mentioned) 2. E>C (p=0.008) 3. E>C (p=0.04) 1. E>C (p=0.003) 2. 1) E>C (p=0.004) 2) E>C (p=0.003) 3) E>C (p=0.195) 4) E>C (p=0.005) 3. E>C (p=0.013) E: higher incidence of injection site reactions (<5%) BV biotherapy resulted in significant improvements in knee OA pain and physical function. NR BV treatment was more effective than AC NR BV therapy was more effective than AC therapy alone. 1. WOMAC 1. E>C (p=0.048) NR BV treatment should be more effective in knee OA 60

7 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 61 ) Table 1. A Characteristics of the Included Studies No. Study Year Country 17 Yang ) China 18 Kwon ) Korea 19 Li ) China 20 Liu ) China Study Size 60 E: BV live (30) 60 E: BV (40) Intervention (n) C: WN (30) C: AC (20) 57 E: BV live (28) C: AC (29) 80 E: BV live (40) C: ET (40) 1. VAS 2. WOMAC 1) pain 2) stiffness 3) function 3. SF-36 Outcomes Results 1. Subjective Pain Relief Score (Excellent, good, fair, poor) 2. Infrared Thermography 1. HSS 1) total 2) pain 3) function 4) muscle strength 5) mobility total 2. TCM syndrome score 1. Effective rate 2. Remarkable effective rate 1. E>C (p=0.001) 2. 1) E>C (p=0.001) 2) E>C (p=0.000) 3) E>C (p=0.007) 3. E>C (p=0.005) 1. E>C (p<0.01) 2. E>C (Statistics not mentioned) 1. 1) E>C (p=0.093) 2) E>C (p=0.046) 3) E=C (p=0.063) 4) E=C (p=0.096) 5) E=C (p=0.257) 2. E=C (p=0.572) 1. E>C (p<0.05) 2. E>C (p<0.05) Adverse event (n) E: Treatment site redness, edema, itching (9) Author's conclusion BV has the most positive effect in improving symptoms of knee OA NR BV was found to have improved therapeutic efficacy as compared to traditional needle acupuncture E: Treatment site redness (1), itching (5) The BV had a more significant clinical efficacy on Knee OA and superior to routine acupuncture therapy especially in the alleviation of pain NR BV treatment has clinical effect. E>C: Experimental group was more effective than control group; E=C: No statistically significant difference between experimental group and control group. AC: Acupuncture; BV: Bee venom; C: Control group; CRP: C-reactive protein; E: Experimental group; EA: Electroacupuncture; ET: Electrotherapy; EQ-5D: EuroQol five-dimensions; HM: Herbal Medicine; HSS: Hospital for Special Surgery; IA: Intra-articular injection IJ: Injection; IV: Intravenous injection; ISOA: Index of Severity for Osteoarthrosis; KHAQ: Korean Health Assessment Questionnaire; M: Medicine; NR: Not reported; OA: Osteoarthritis; PA: Pharmacopuncture; PGA: Patient Global Assessment; PhGA: Physician Global Assessment; PPI: Present Pain Intensity; SF-36: 36-Item Short Form Survey; SF-MPQ: Short-Form McGill Pain Questionnaire; TCM: Traditional Chinese medicine; VAS: Visual analogue scale; WN: Warm needling; WOMAC: Western Ontario and McMaster Universities Osteoarhtirits Index 61

8 ( 62 ) Journal of Korean Medicine 2020;41(1) Table 2. Intervention, Acupoints, and Duration of the Included Studies No. Study Year Experimental group Control group Acupoints 1 Shin PA : Chinemys reevesii gray (4ml) IJ: 5% dextrose (4ml) ST35, ST34, SP9, SP10, GB34, LR8, ) EX-LE4, EX-LE2 Treatment N⁰ /Total Period 2 Kim PA : Root Bark of Ulmus davidiana Planch IJ: Normal saline ST35, EX-LE4, EX-LE2, Ashi point 12X ) /6 weeks 3 Park PA : Homnis placenta ) (0.1ml each point) 4 Yu PA: Cnidium officinale ) (2ml) 5 Sun PA: Compound Angelica ) (0.5~1ml each point) 6 Cai PA: Salvia miltiorrhiza (3~5ml) ) +IA: sodium hyaluronate 7 Hua PA: Shuxuening 舒血宁 (2ml) ) +lidocaine (0.5ml) +IV: 鹿瓜多肽 (16mg) + 血栓通 (150mg*2) 8 Gao PA: Salvia miltiorrhiza (1ml) ) +M: Celecoxib (0.2g) +IA: Sodium hyaluronate (2ml) 9 Ye PA: Angelica (2ml) ) +WN: Stainless steel needle (0.30*40mm) +Moxibustion 10 Zhang PA : Salvia miltiorrhiza (2ml) ) +AC: Stainless steel needle (0.30*40mm) 11 Liu PA: Salvia miltiorrhiza (2ml) ) +EA: Stainless steel needle (0.30*40mm) AC: Stainless steel needle (0.30*40mm) BL24, EX-LE4, ST35, GB34, SP10, ST34, Ashi point IJ: Triamcinolone +lidocaine AC: Stainless steel needle (0.25*40mm) M: Medicine (celecoxib 0.2g bid) 6X /3 weeks 6~9X /3 weeks EX-LE2, EX-LE4, ST35 18X /4 weeks ST34, SP10, SP9, GB34 12X /4 weeks IA : Sodium hyaluronate SP10, ST34, GB34, SP9, EX-LE4, ST35 5X /5 weeks IV: 鹿瓜多肽 (16mg) + 血栓通 (150mg*2) Ashi point (around the knee) 4X /2 weeks M: Celecoxib (0.2g) +IA: Sodium hyaluronate (2ml) M: Diclofenac sodium (25mg tid) +WN: Stainless steel needle (0.30*40mm) +Moxibustion SP10, BL17, ST36, GB39, GB33, KI3 30X /10 weeks PA: ST35, ST34, ST36, GB34 WN: EX-LE4, ST35, EX-LE2, ST34, SP10, LR8, LR7, GB33, SP9, GB34, ST36 AC: Stainless steel needle (0.30*40mm) PA: SP10, GB34 AC: EX-LE4, ST35, SP10, ST34, GB34, SP9 EA: Stainless steel needle (0.30*40mm) PA: GB34, BL11 EA: GB34, ST34, SP10, EX-LE4, ST35, SP9 28X /4 weeks 6X /2 weeks 18X /6 weeks 12 Li PA: Angelica (2ml) +placenta (2ml) ) +HM: Dokwhalgisaengwhan 13 Conrad BV: Honey bee venom (HBV) ) biotherapy (100 μg each) HM: Dokwhalgisaengwhan ST36, SP10, BL40, GB34, SP9 7X /2 weeks IJ: Histamine phosphate dermal injection (2.75 μg each) Knee top, EX-LE4, ST35, ST34, BL40, BL19, BL21, BL24, BL25, BL27 15X /15 weeks 62

9 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 63 ) Table 2. Intervention, Acupoints, and Duration of the Included Studies No. Study Year 14 Lee BV: Dry bee venom dissolved in saline ) (3000:1/ cc) 15 Ryu BV: Dry bee venom dissolved in saline ) (0.005%/ cc) 16 An BV: Dry bee venom dissolved in saline ) (3000:11/ cc) Experimental group Control group Acupoints AC: Stainless steel needle (0.25*30mm) BV: EX-LE4, ST35, Ashi point AC: EX-LE2, EX-LE4, ST35, ST36, LR3, ST34, SP10 AC: Stainless steel needle (0.25*50mm) BV: IA, Ashi point AC: EX-LE2, ST35, EX-LE4, ST34, ST36, GB34 AC: Stainless steel needle (0.25*40mm) BV: IA, Ashi point AC: EX-LE2, EX-LE4, ST35, GB34, LR3, ST34, SP10 17 Yang BV: Pick live bees WN: Stainless steel needle (0.30*40mm) BV: EX-LE4, ST35, SP10, ST34, ) WN: ST35, EX-LE4, SP10, ST34, GB33, GB34, SP9, ST36 18 Kwon BV: Dry bee venom dissolved in saline ) (dilute to 0.03%/0.1ml each point) AC: Stainless steel needle (0.25*30mm) SP10, ST34, ST36, GB34, LR3, EX-LE2, ST35 19 Li BV: Pick live bees AC: Stainless steel needle (0.30*40mm) BV: Ashi point, EX-LE4, ST35, GB ) AC: Ashi point, EX-LE4, ST35, GB34, SP10, SP9 20 Liu BV: Pick live bees ET: Electrotherapy ) Ashi point, EX-LE4, ST35, SP10, ST36, ST32, ST34, BL40, GB34, SP9, LR8, BL24 Treatment N⁰ /Total Period NR /NR 12X /4 weeks NR /NR 10X /5 weeks 8X /4 weeks 5X /2 weeks 10X /4 weeks AC: Acupuncture; BV: Bee venom; C: Control group; E: Experimental group; EA: Electroacupuncture; ET: Electrotherapy; HM: Herbal Medicine; HSS: Hospital for Special Surgery; IA: Intra-articular injection IJ: Injection; IV: Intravenous injection; M: Medicine; PA: Pharmacopuncture; WN: Warm needling. 63

10 ( 64 ) Journal of Korean Medicine 2020;41(1) 탈락자가발생한연구는 5편이었으며, 5편모두탈락사유를보고하였다. Zhang의연구 27) 에서는중재군 4명 ( 치료중단 1명, 동의철회 3명 ) 및대조군 2명 ( 치료중단 2명 ) 으로총 6명이탈락하였고, Shin 등의연구 18) 에서는각군이명확하게기재되지않은가운데총 8명 ( 치료미준수 4명, 금지약물복용 2명, 치료중단 2명 ) 이탈락하였다. Conrad 등의연구 30) 에서는중재군 113명 ( 이상반응 34명, 심각한이상반응 2명, 치료미준수 20명, 동의철회 43명, 사후평가소실 11명, 기타 3명 ) 및대조군 35명 ( 이상반응 3명, 심각한이상반응 2명, 치료미준수 10명, 동의철회 14명, 사후평가소실 4명, 기타 2명 ) 으로많은수가탈락하였다. Kim 등의연구 19) 에서는중재군 1 명 ( 치료중단 ) 및대조군 6명 ( 치료중단 1명, 교통사고로인한치료중단 2명, 사후평가소실 3명 ) 으로총 7명이탈락하였다. Li의연구 36) 에서는중재군 2명 ( 동의철회 1명, 이상반응 1명 ), 대조군에서는 1 명 ( 금지약물복용 ) 으로총 3명이탈락하였다. 3) 중재분석두드러기, 가려움증, 경련, 설사등의아나필락시스가능성이높은봉독요법의경우연구방법및절차상차이발생가능성이높기에봉독과약침을구분하여중재분석을시행하였다. 즉, 1차로봉독과약침을구분한가운데 2차로한, 양방치료의단독치료및병행치료여부로세분화하였다. 약침요법은단독치료의경우, 거짓약침치료와비교 2편 18,19), 침치료와비교 1편 20), 양방치료와비교 2편 21,22) 이었으며, 병행치료의경우, 양방치료시약침치료여부에따른비교 3편 23-25), 한방치료시약침치료여부에따른비교 4편 26-29) 으로총 12편으로나타났다. 봉독요법은단독치료의경우, 거짓봉독약침치료와비교 1편 30), 침치료와비교 6편 31-36), 양방치료와비교 1편 37) 이었다. 총 12편의약침연구중 4편 23,25,27,28) 이단삼주사액, 2편 22,26) 이당귀주사액을사용하였으며, 당귀와태반주사혼합액, 구판약침, 자하거약침, 천궁주사액, 은행잎추출물, 유근피약침을사용한연구가각 1편씩이었다. 봉독연구에서는 5편 30-33,35) 의연구가건조봉독을생리식염수로희석하여사용하였으며, 3 편 34,36,37) 의연구에서는살아있는벌을이용하여환부및경혈을직접자극하는방법을사용하였다. 4) 평가지표약침및봉독요법의효과를평가하기위해 VAS (Visual Analogue Scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) 각 9회, Effective rate가 8회로가장많이이용된가운데, SF-36 (The Medical Outcomes Study Short Form-36) 2회, Lysholm score 2회, SF-MPQ (short-form McGill pain questionnaire) 1회, EQ-5D (EuroQol five-dimensions) 1회등이평가지표로사용되었다. 5) 치료횟수및기간 1주당 2~3회치료가 15편으로가장많은가운데, 주당 1회치료 2편 23,30), 3.5회치료 1편 29), 4.5회치료 1편 21), 7회치료 1편 26) 으로확인하였다. 치료기간은 2주 4편 24,27,29,36), 3주 2편 18,20), 4주 6편 21,22,26,32,35,37), 5주이상 6편 19,23,25-28,30,34) 순이었고, 가장긴치료기간은 15주였다 30). 한편치료기간이명시되지않고주당 2-3회치료를언급한논문은 2편 31,33) 이었다. 6) 치료혈위 20편의연구에서중재군에치료시행시선택된혈위를분석한결과, 犢鼻 (= 外膝眼, ST35) 가 12회로가장많이선택되었고, 陽陵泉 (GB34) 11회, 內膝眼 64

11 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 65 ) (EX-LE4) 과血海 (SP10) 10회순으로선택되었다. 그외梁丘 (ST34), 阿是穴, 足三里 (ST36), 陰陵泉 (SP9) 또한 5회이상선택되었다 (Table 3). 7) 안전성약침및봉독요법에서이상반응을보고한연구는총 6편으로, 치료부위에서피부가려움증, 부종, 발적등을보고한논문이 5편 19,25,30,34,36), 소량의피하출혈을보고한연구 1편 27), 구역감을보고한연구가 1편 19) 이었다. 이중봉독을이용한 1편의연구 30) 는중재군과대조군모두에서심각한부작용 ( 아나필락시스, 흡인성폐렴, 게실염, 동서맥 ) 을보고하였다. 3. 치료의유효성분석 (Appendix 참고 ) 1) 약침 (1) 약침요법 vs. 거짓약침 12편의약침논문중거짓약침과비교한연구는 2편 18,19) 이나이중분석이가능한논문은 1편 18) 이었다 (sham: 5% dextrose). 1편을통한 Pain VAS, WOMAC, EQ-5D 평가모두에서약침요법군이거짓약침군에비해유의한효과를보였다 (Pain VAS: MD -1.80, 95% CI to -9.84, p=0.0003; WOMAC: MD , 95% CI to -1.99, p=0.02; EQ-5D: MD -0.90, 95% CI to -0.08, p=0.03). (2) 약침요법 vs. 한방치료 1편의논문 20) 이있었으나본연구에서분석가능한평가지표가없고평균및표준편차가제시되지않아분석을시행하지못하였다. (3) 약침요법 vs. 양방치료약침요법과양방치료를비교한연구는 2편 21,22) 으로, effective rate만을평가지표로사용하였다. 그결과, 약침요법군이대조군에비해호전을보였으나통계적으로유의하지않았다 (RR 1.10, 95% CI 0.95 to 1.27, p=0.22). (4) 약침요법 + 양방치료 vs. 양방치료양방치료를병행한상태에서약침요법의유무를비교한연구는총 3편 23-25) 으로, Pain VAS, WOMAC, effective rate 평가를사용하였다. Pain VAS와 WOMAC 평가가각 3편, 2편에서시행되었고, 약침요법병행군이양방치료단독에비해유의한효과를보였다 (Pain VAS: MD -1.02, 95% CI to -0.86, p< ; WOMAC: MD , 95% CI to , p< ). Effective rate는 1편에서사용되었고, 약침요법군이더많은호전을보 Table 3. Frequency of Acupoints Frequency Acupoints Frequency Acupoints 12 ST35 4 EX-LE2 11 GB34 3 BL40 10 EX-LE4 3 BL24 10 SP10 2 LR8 9 ST Ashi point LR3, BL11, BL17, BL19, BL21, BL25, BL27, GB33, 5 ST36 GB39, KI1, ST32 SP9 Total 23 acupoints 65

12 ( 66 ) Journal of Korean Medicine 2020;41(1) 였으나통계적으로유의하지않았다 (RR 1.03, 95% CI 0.94 to 1.13, p=0.47). (5) 약침요법 + 한방치료 vs. 한방치료한방치료를병행한상태에서약침요법의유무를비교한연구는총 4편 26-29) 으로, Pain VAS, WOMAC, effective rate 평가를사용하였다. Pain VAS와 effective rate 평가가각 2편, 4편에서시행되었고, 약침요법군이유의한효과를보였다 (Pain VAS: MD -1.27, 95% CI to -1.13, p< ; effective rate: RR 1.22, 95% CI 1.10 to 1.35, p=0.0001). WOMAC은 1편에서사용되었고, 약침요법군이더많은호전을보였으나통계적으로는유의하지않았다 (MD -5.57, 95% CI to 3.29, p=0.22). (6) 다용약침별분석 2회이상사용한약침은단삼과당귀로, 각약침액에대한평가지표별분석을시행하였다. 단삼약침을이용한연구는양방및한방치료를병행한상태에서효과를비교한 4편의연구 23,25,27,28) 로 VAS, WOMAC, effective rate 평가를사용하였다. VAS와 WOMAC 평가가각 4편, 2편에서시행되었고, 단삼약침요법군이유의한효과를보였다 (VAS: MD -1.16, 95% CI to -1.05, p< ; WOMAC: MD-7.08, 95% CI to -3.66, p<0.0001). Effective rate는 2편에서사용되었고, 약침요법군이더많은호전을보였으나통계적으로는유의하지않았다 (RR1.09, 95% CI 0.98 to 1.22, p=0.10). 당귀약침을이용한연구는양방치료와비교한 1 편 22) 과한방치료를병행한상태에서효과를비교한 1편의연구 26) 로 effective rate 평가를사용하였다. Effective rate는당귀약침요법군이유의한효과를보였다 (RR 1.19, 95% CI 1.04 to 1.36, p=0.01). 2) 봉독 (1) 봉독요법 vs. 거짓봉독 8편의봉독논문중거짓봉독과비교한연구는 1 편 30) 으로 (placebo: histamine phosphate), 이를통한 Pain VAS (walking and resting), WOMAC (pain and function) 평가가시행되었다. 그결과, resting 시 Pain VAS 제외한나머지평가에서봉침요법군이유의한효과를보였다 (Pain VAS walking: MD -0.90, 95% CI to -0.32, p=0.002; Pain VAS resting: MD -0.30, 95% CI to 0.24, p=0.27; WOMAC pain: MD -1.10, 95% CI to -0.28, p=0.008; WOMAC function: MD -3.10, 95% CI to -0.28, p=0.03). (2) 봉독요법 vs. 한방치료봉독요법과한방 ( 침 ) 치료를비교한연구는 6편 31-36) 이나이중메타분석이가능한논문은 4편 31-34) 이었다. 4편을통한 VAS, WOMAC (total, pain, stiffness, function), SF-36, effective rate 평가가시행되었는데이중 SF-36을제외한나머지평가가 2편이상에서시행되었다. 그결과, effective rate를제외한나머지 VAS, WOMAC total, pain, stiffness, function, SF36 평가에서봉침요법군이유의한효과를보였다 (VAS: MD , 95% CI to -7.75, p< ; WOMAC total: MD -8.59, 95% CI to -3.74, p=0.0005; WOMAC pain: MD -1.64, 95% CI to -0.99, p< ; WOMAC stiffness: MD -0.84, 95% CI to -0.43, p<0.0001; WOMAC function: MD -6.65, 95% CI to -3.18, p=0.0002; SF-36: MD 3.20, 95% CI 1.22 to 5.18, p=0.002). Effective rate는봉독요법군이대조군에비해많은호전을보였으나통계적으로는유의하지않았다 (RR 1.06, 95% CI 0.97 to 1.16, p=0.21). 66

13 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 67 ) (3) 봉독요법 vs. 양방치료봉독요법과양방치료를비교한연구는 1편 37) 으로, effective rate 평가에서봉독요법군이유의한효과를보였다 (RR 1.28, 95% CI 1.03 to 1.57, p=0.02). 1. 약침 1) 약침 vs. 거짓약침 Appendix Pain VAS WOMAC total EQ-5D 67

14 ( 68 ) Journal of Korean Medicine 2020;41(1) 2) 약침 vs. 양방치료 Effective rate 3) 약침 + 양방치료 vs. 양방치료 Pain VAS WOMAC total 68

15 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 69 ) Effective rate 4) 약침 + 한방치료 vs. 한방치료 Pain VAS WOMAC total 69

16 ( 70 ) Journal of Korean Medicine 2020;41(1) Effective rate 5) 단삼약침 + 양방 / 한방치료 vs. 양방 / 한방치료 VAS WOMAC total Effective rate 70

17 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 71 ) 6) 당귀약침 vs. 타치료 Effective rate 2. 봉독 1) 봉독 vs. 거짓봉독 Pain VAS (walking) Pain VAS (resting) 71

18 ( 72 ) Journal of Korean Medicine 2020;41(1) WOMAC pain WOMAC function 2) 봉독 vs. 한방치료 VAS 72

19 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 73 ) WOMAC total WOMAC pain WOMAC stiffness WOMAC function 73

20 ( 74 ) Journal of Korean Medicine 2020;41(1) SF-36 Effective rate 3) 봉독 vs. 양방치료 Effective rate 4. 비뚤림위험평가본연구에서선정된 16편의연구모두 RCT로, RoB tool을이용하여비뚤림위험을평가하였다. 무작위배정순서의생성항목에서는 8편 18,22,24-28,34) 이동전던지기나, 난수테이블같은적절한무작위배정 방법을사용하여비뚤림위험 낮음 으로평가하였고, 무작위방법을사용하였으나, 구체적방법이기재되어있지않은 8편 21,23,29-33,37) 은비뚤림위험 불확실 로평가하였다. 배정순서의은폐항목에서는무작위로카드를배분한 3편 22,26,27) 은비뚤림위험 74

21 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 75 ) Fig. 2. Risk of bias summary and graph (+), Low risk of bias; ( ), High risk of bias; (?), Unclear of bias. 낮음 으로평가하였고, 기재되어있지않은 13편 18,21,23-25,28-34,37) 은비뚤림위험 불확실 로평가하였다. 연구참여자및연구자에대한눈가림항목에서는연구의디자인을모두알고있는연구자에의해실험군과대조군중재가준비된논문 1편 30) 을비뚤림위험 낮음 으로평가하였고, 나머지 15편의연구에서눈가림에관한언급이없었지만, 약침 ( 봉독 ) 이라는중재시술의특성상눈가림이불가능할것이라판단되어비뚤림위험 높음 으로평가하였다. 결과평가에대한눈가림항목에서는 16편모두특별한언급이없어비뚤림위험 불확실 로평가하였다. 불완전한결과자료항목에서는결측치가발생하지않은 13편과결측치가발생하였으나탈락원인을기술한 3편에모두비뚤림위험 낮음 으로평가하였다. 선택적보고항목에서는 16편모두프로토콜은없지 만예상되는모든결과를보고한것으로보아비뚤림위험 낮음 으로평가하였다 (Figure 2). 고찰 Knee OA는슬관절내물리적부하의증가및연골세포대사변화등의이유로관절연골과주위구조물이변형되는질환으로 38), 지속적인염증대비자체치유능력이제한됨에따라골관절이변형된다는특징을갖는다 39). 증상으로는일반적인통증, 부종, 관절범위의제한뿐만이아닌, 신체적기능저하와정신적문제를동반한건강관련삶의질 (health -related quality of life) 도영향을줄수있는가운데 40), 국내에서는다빈도질병 10위안에드는질환이다. 또한국민건강보험공단 2017년도자료에의하면 65세이상의경우입원, 외래환자수 5위에속하였고 75

22 ( 76 ) Journal of Korean Medicine 2020;41(1) 그증가율도 10% 내외이며, 한방진료요양급여현황에서도입원환자수 4위를차지하였다 41). 한편, 관절염환자의 2/3 이상이한의학을포함하는대체보완의학을이용하는것으로보고된가운데 42), 약침은치료경혈및체표반응점에특정한약에서정제추출한약물을주입하는것으로자침과약물의효과를동시에얻는장점이있어한방임상에서폭넓게활용되고있는치료법이다 43). 봉독의경우 melittin, apamin, phospholipase A2 등의생화학적성분을함유한것으로알려져있으며 44), 슬관절염동물모델에서그진통기전을확인한연구가보고되었다 45). 이와같이약침및봉독요법은 knee OA 에서치료목적으로사용될가능성이높은한의학적치료중에하나로예상된다. 이러한약침및봉독요법에대한 SR의경우, Park 2009 등 46) 은국내 38개의약침 RCT를통해약침의적응증을 knee OA, 급성족관절염좌, 요각통, 경항통등의근골격계질환이라고제안하였고, Lee 등14), Gu 등 47) 은외상성손상, knee OA에대한봉독 SR을통해통증및관절범위제한개선을위해단독침치료에우선하여봉독요법이고려될수있다고보고하였다. 그리고국외의경우 (Park 2016 등 ) 약침을이용한 RCT에대한 SR 및메타분석을통해근골격계질환및비만에약침사용가능성을보고하였다 48). 하지만 Park ) 및 Park 2016 등 47) 은약침주제의 RCT 각각 38, 29편을고찰하였으나 knee OA 대상이아니었고, Lee 등 14) 은봉독을주제로 29편을고찰하였으나이중 RCT는 10편이었고, 외상성손상이주제였다. Gu 등 47) 은 knee OA에대한봉독 SR을시행하였으나총 13편의연구및 827명의연구대상자로그규모가작은편이었고여기에 non-rct를포함하고, 선정된연구의비뚤림위험이높은논문들이많다는한계점이있었다. 이에 knee OA에대한약침및봉독요법의 SR을시행하였고, 본연구에서는기존연구보다많은편수 (20 편 ) 및연구대상자 (1536명) 를포함한결과를얻을수있었다. 본논문은미리정한선정기준에따라 20개의논문을선별하였다. 기존의봉독혹은 knee OA SR 9,47) 이 3~13개였던것을비교하면 20개의논문이나온것은의미가있다. 하지만 3개국에국한되어있고, 50% 이상이중국논문이기때문에광범위한지역에서약침및봉독요법이실행되지못하였음을의미한다. 또한연구의대상자수는 50명이하가 2편, 50~100명인연구가 17편, 100명이넘는연구가 1편으로대부분 100명이내의연구위주였다. 엄격하게수행된연구일지라도대상자의수가작으면통계적유의성을신뢰하기어렵기때문에적절한수의대상자모집이필요함을의미한다. 본연구에사용된약침제제의종류는구판 ( 龜板, Chinemysreevesii Gary), 천궁 ( 川芎, Cnidium officinale), 당귀 ( 當歸, Angelica), 단삼 ( 丹蔘, Salvia miltiorrhiza), 자하거 ( 紫何車, Homnis placenta), 은행잎 ( 舒血宁, Shuxuening), 유근피 ( 柳根皮, Chinemysreevesii gray) 였다. 본초학에서각기다른분류에속하지만여러연구를통해구판의중간엽줄기세포의증식및골형성단백질촉진효과와 49) 천궁의성분인 Cnidilide, Ligustilide, Senkyunolide의중추성근육의이완효과 50), 당귀의슬관절주위근육의강직감완화와관절내미세혈류순환개선효능 21) 을확인할수있다. 그리고단삼의성분인 salvianolic acid B를통한항염증및신경보호효과 51), 자하거의관절염에서의조직손상완화, cytokines 억제및 inos 효소활성억제효과 52), 은행잎을통한관절낭액의 IL-1β 및 TNF-α의수치를낮추는효과 53), 관절염유발동물모델에서유근피의항염증작용 54) 등이보고되어있다. 봉독의경우 40여성분이포함되어있으며, 이중봉독약침의진통소염효과를나타내는주요성분 76

23 퇴행성슬관절염에대한약침및봉독요법의효용성및안전성 : 체계적문헌고찰및메타분석 ( 77 ) 은 melittin, apamin 등으로이는혈중 cortisol의농도를증가시키고프로스타글란딘의생합성을억제하는등국소적진통소염작용이있는것으로보고되었다 55). 또한많은관절염동물모델에서약침이 cytokine 등염증관련지표를감소시키고병리조직학적관절연골의염증및연골세포의소실을억제하는것이보고되었고 12), 관절강주사에호전되지않은 OA환자치험례 56) 도보고되어있을정도로그효능을확인할수있다. 이에다양한약침제제를이용하여약침을제조할수있고, 환자의변증을통한약침의사용가능성을확인할수있었다. 치료횟수및기간의경우, 주당 2~3회의시술을시행한연구가 15편으로가장많았고, 기간은 4주의치료기간을제시한논문이 6편으로가장많았다. Shin 등 18) 의연구와 Ryu 등 32) 의연구에서는치료직후보다추적관찰시더높은치료효과를나타내었으며, Conrad 등 30) 의연구에서도 PGA, PhGA평가항목의효과가치료종료후 4주간의추적관찰기간동안유지됨을보고하였다. 이는약침의일정기간의지속성을확인할수있는근거가되지만, 병기자체가길고호전이쉽지않은 knee OA의특성상더연장된추적관찰기간이필요하다 57). 예로 Witt 등 58) 은 8주의치료기간, 52주의추적관찰기간을시행한것을확인할수있다. 선혈의경우, 犢鼻 (= 外膝眼, ST35), 陽陵泉 (GB34), 內膝眼 (EX-LE4), 血海 (SP10) 가 10회이상사용되었는데, 이는슬관절의해부학적인구조와밀접한연관이있다. 이는임상에서선혈기준으로통증등에영향을주는해부학적구조물을한의사들이많이사용한다 (32.6%) 는보고서의내용과도부합하며 59), 陽陵泉 (GB34) 은프롤로주사주요 4개포인트중에하나로사용되는점 60) 과血海 (SP10) 는 knee OA 치료를위한히알루론산액이주입되는슬개골상내측부 61) 와유사하다는점과도일맥상통한다. 평가척도는각연구마다다양하게사용되었는데 WOMAC과 VAS가각 9회, Effective rate가 8회로가장많이사용되었으며 SF-36, EQ-5D는각 2, 1회사용되었다. 유효율의경우치료결과를단순히완쾌, 효과, 유효, 무효등으로나누어평가하여그효과를정량적으로나타낼수없고, VAS는간편하다는장점은있으나기능적인면을확인하기어렵다는단점이있다. 이에 WOMAC, Lequesne's index와같이민감도가높고, 신뢰도와타당도에대한검증이잘되어있는기능평가척도와 62) SF-36, EQ-5D 등의삶의질척도와같이다방면의평가척도를통한 knee OA 환자의파악이필요할것으로예상된다. 또한향후연구에서는많은대상자수와장기간의치료및추적관찰기간, 그리고거짓대조군설정등을통해약침및봉독요법활용에대한보다체계적인연구설계가필요할것으로사료된다. 본연구에포함된 20편의논문중거짓치료를대조군으로설정한연구는 3편 18,19,30) 으로약침에대해 5% dextrose 혹생리식염수를거짓약침으로설정하거나, 봉독약침에대해히스타민을거짓약침으로설정해그효능을검증하고자하였다. 거짓약침으로설정된약물들은침감이비슷하여피험자맹검유지가가능하다고판단되며, 두연구모두에서중재군이대조군보다통계적으로유의한효과를보여약침혹봉독자체의효과를파악할수있었다. 하지만논문편수가부족하여약침혹봉독의효과를확고히증명하기에는부족함이따른다. 향후거짓약침을대조군으로설정한연구가더필요하다고사료된다. 16편대상의메타분석에서약침요법은단독치료의경우, 거짓약침치료와비교 1편 18), 양방치료와비교 2편 21,22) 으로분석을수행하였다. 이에약침요법은 knee OA 치료에있어거짓약침보다슬관절통증감소, 기능개선, 삶의질향상같이임상적으로유의미한결과를나타내었다. 병행치료의경우, 77

24 ( 78 ) Journal of Korean Medicine 2020;41(1) 양방치료시약침치료여부에따른비교 3편 23-25), 한방치료시약침치료여부에따른비교 4편 26-29) 을수행하였는데약침치료를추가적으로수행하였을때, 슬관절통증감소, 기능개선, 증상호전같이임상적으로유의미한결과를나타내었다. 봉독약침의경우거짓봉독치료와비교 1편 30), 침치료와의비교 4편 31-34), 양방치료와의비교 1편 37) 으로분석을수행한결과, 거짓봉독치료보다슬관절통증감소, 기능개선에서유의미한결과를나타내었으며, 침치료와의비교에서슬관절통증감소, 기능개선, 삶의질향상에서유의미한결과를나타내었다. 양방치료와의비교에서도증상호전을나타내었다. 하지만모든분석에서논문의개수가 4 개이하로절대적인논문과대상자수가부족하여비정밀성이높아명확한결론을내리기에는한계가있다. 비뚤림위험을분석한결과, 대다수의연구에서무작위배정순서의생성항목에서동전던지기나난수테이블같은적절한방법을사용하여비뚤림위험이낮았으나, 배정순서의은폐항목에서는기재되지않아비뚤림위험이불확실한연구가많았다. 연구참여자및연구자에대한눈가림과결과평가에대한눈가림에대한언급이부족하였는데이는한의학적치료수단의특성으로인해이중눈가림을효과적으로설계하는데한계가있었기때문으로사료된다. 본연구를통해국내외에서 knee OA에사용한약침의종류를파악하고, 치료횟수나기간, 그리고선혈점을확인함으로써임상에서의활용도를높이고, 대조군대비약침및봉독요법의유효성을확인함으로써그사용의당위성도갖추었다는점에큰의의가있다. 하지만선별연구표본수가부족하고, 발행국가가다양하지못한점은본연구의한계이다. 또한향후연구에서는많은대상자수와장기간의치료및추적관찰기간, 그리고거짓대조군설정 등을통해약침및봉독요법활용에대한보다체계적인연구설계가필요할것으로사료된다. 감사의글 This study was supported by the Traditional Korean Medicine R&D Program funded by the Ministry of Health & Welfare through the Korea Health Industry Development Institute (KHIDI) (grant No.: HB17C0003). 결론 Knee OA에대한약침및봉독요법의효과를객관적으로평가하기위해체계적문헌고찰을진행한결과다음과같은결론을얻었다. 1. 체계적문헌고찰에포함된 20편중국내에서발간된논문은 7편이었으며, 단삼과당귀를사용한논문이각 4편과 2편이었고, 당귀와태반혼합액, 구판, 자하거, 천궁, 은행잎, 유근피를사용한논문이각각 1편이었다. 봉독약침을활용한방법은건조봉독을생리식염수에희석하여사용한논문이 5편, 살아있는벌을사용한논문이 3편이었다. 2. 약침 ( 봉독 ) 의치료기간은 4주, 치료횟수는주당 2~3회, 치료혈위는犢鼻 (= 外膝眼, ST35), 陽陵泉 (GB34), 內膝眼 (EX-LE4), 血海 (SP10) 가가장많았다. 3. 본연구의메타분석결과약침및봉독치료는 knee OA 치료에있어기존의치료보다슬관절통증감소, 기능개선, 강직감감소등과같이임상적으로유의미한결과를나타내었다. 안전성측 78

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