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JKM > Volume 41(1); 2020 > Article
Lee, Jo, Kim, Sung, and Kim: Efficacy and Safety of Pharmacopuncture and Bee venom Acupuncture for Knee Osteoarthritis: A systematic review and meta-analysis

Abstract

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.

ACKNOWLEDGMENTS

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).

Fig. 1
Flow chart of the trial selection process
jkm-41-1-55f1.gif
Fig. 2
Risk of bias summary and graph
(+), Low risk of bias; (−), High risk of bias; (?), Unclear of bias.
jkm-41-1-55f2.gif
Table 1
A Characteristics of the Included Studies
No. Study Year
Country
Study Size Intervention (n) Outcomes Results Adverse event (n) Author’s conclusion
1 Shin 201518)
Korea
40 E: PA (20) C: Placebo (20)
  1. SF-MPQ

    1. VAS

    2. PPI

    3. sensory

    4. affective

  2. WOMAC

  3. EQ-5D

    1. E>C (p=0.000)

    2. E>C (p=0.049)

    3. E>C (p=0.004)

    4. E=C

  1. E>C (p=0.004)

  2. E>C (p=0.020)

NR PA therapy can be an effective treatment in knee OA
2 Kim 201019)
Korea
53 E: PA (29) C: Placebo (24)
  1. VAS

  2. WOMAC

  3. KHAQ

  4. SF-36

  1. E=C

  2. E=C

  3. E=C

  4. E=C

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.
3 Park 200620)
Korea
60 E: PA (30) C: AC (30)
  1. Lysholm score

  2. Nine point scale

  1. E=C

  2. E>C (Statistics not mentioned)

NR PA was not more effective than Filiform acupuncture statistically.
4 Yu 200221)
China
60 E: PA (30) C: IA (30)
  1. Effective rate

  2. Intra bony pressure

  1. E>C (p<0.05)

  2. E>C (p<0.05)

NR PA can significantly improve symptoms and sign of knee OA
5 Sun 200922)
China
58 E: PA (20) C1: AC (20)
C2: Medicine (18)
  1. Effective rate

  2. ISOA

  3. Serum NO levels

  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)

NR PA in treating knee OA is safe and effective, the course of treatment no side effects.
6 Cai 201323)
China
60 E: PA+IA (30) C: IA (30)
  1. VAS

  2. Lysholm score

  3. Effective rate

  1. E>C (p<0.01)

  2. E>C (p<0.05)

  3. E>C (p<0.05)

NR PA+IA is an effective method in treating knee OA
7 Hua 201424)
China
60 E: PA+IV (30) C: IV (30)
  1. VAS

  2. WOMAC

  1. E>C (p<0.05)

  2. E>C (p<0.05)

NR PA+IV can be applicable to improve symptoms.
8 Gao 201825)
China
80 E: PA+IA
+Medicine (40)
C: IA
+Medicine (40)
  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)

E : itching (2), rash (2)
C : itching (2), rash (1)
PA+IA improve knee joint function, suppress local inflammatory response. worthy of clinical application
9 Ye 201126)
China
90 E: PA+WN (30) C1: Medicine (30)
C2: WN (30)
  1. Effective rate

  1. E>C1, C2 (p=0.000)

NR PA+WN has more significantly clinical effect in treating Knee OA
10 Zhang 201427)
China
60 E: PA+AC (30) C: AC (30)
  1. VAS

  2. WOMAC

  3. Knee circumstance score

  1. E>C (p=0.043)

  2. E>C (p=0.045)

  3. E>C (p=0.026)

E: Bruise (3)
C: Bruise (3)
PA+AC has shown in terms of overall improvement in symptoms
11 Liu 201528)
China
60 E: PA+EA (30) C: EA (30)
  1. VAS

  2. Lysholm score

  3. Effective rate

  1. E>C (p<0.01)

  2. E>C (p<0.01)

  3. E>C (p<0.05)

NR PA+EA is more effective better than EA only.
12 Li 201629)
China
100 E: PA+HM (50) C: HM (50)
  1. Effective rate

  1. E>C (p<0.05)

NR PA is effective in treating knee osteoarthritis
13 Conrad 201930)
USA
367 E: BV (234) C: Placebo (133)
  1. WOMAC

    1. pain

    2. fuction

  2. VAS

  3. PGA, PhGA

    1. E>C (p=0.001)

    2. E>C (p=0.0046)

  1. E>C (p<=0.0012)

  2. E>C (p=0.0015)

E: higher incidence of injection site reactions (<5%) BV biotherapy resulted in significant improvements in knee OA pain and physical function.
14 Lee 200331)
Korea
50 E: BV (25) C: AC (25)
  1. Effective rate

  2. Nine-point scale

  3. Grade of clinical symptoms

  1. E>C (Statistics not mentioned)

  2. E>C (p=0.008)

  3. E>C (p=0.04)

NR BV treatment was more effective than AC
15 Ryu 200432)
Korea
51 E: BV (26) C: AC (25)
  1. VAS

  2. WOMAC

    1. total

    2. pain

    3. stiffness

    4. function

  3. Lequesne’s index

  1. E>C (p=0.003)

    1. E>C (p=0.004)

    2. E>C (p=0.003)

    3. E>C (p=0.195)

    4. E>C (p=0.005)

  2. E>C (p=0.013)

NR BV therapy was more effective than AC therapy alone.
16 An 200633)
Korea
30 E: BV (17) C: AC (13)
  1. WOMAC

  1. E>C (p=0.048)

NR BV treatment should be more effective in knee OA
17 Yang 201334)
China
60 E: BV live (30) C: WN (30)
  1. VAS

  2. WOMAC

    1. pain

    2. stiffness

    3. function

  3. SF-36

  1. E>C (p=0.001)

    1. E>C (p=0.001)

    2. E>C (p=0.000)

    3. E>C (p=0.007)

  2. E>C (p=0.005)

E: Treatment site redness, edema, itching (9) BV has the most positive effect in improving symptoms of knee OA
18 Kwon 200135)
Korea
60 E: BV (40) C: AC (20)
  1. Subjective Pain Relief Score (Excellent, good, fair, poor)

  2. Infrared Thermography

  1. E>C (p<0.01)

  2. E>C (Statistics not mentioned)

NR BV was found to have improved therapeutic efficacy as compared to traditional needle acupuncture
19 Li 201436)
China
57 E: BV live (28) C: AC (29)
  1. HSS

    1. total

    2. pain

    3. function

    4. muscle strength

    5. mobility total

  2. TCM syndrome score

    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)

  1. E=C (p=0.572)

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
20 Liu 201437)
China
80 E: BV live (40) C: ET (40)
  1. Effective rate

  2. Remarkable effective rate

  1. E>C (p<0.05)

  2. E>C (p<0.05)

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

Table 2
Intervention, Acupoints, and Duration of the Included Studies
No. Study Year Experimental group Control group Acupoints Treatment N°/Total Period
1 Shin 201518) PA : Chinemys reevesii gray (4ml) IJ: 5% dextrose (4ml) ST35, ST34, SP9, SP10, GB34, LR8, EX-LE4, EX-LE2 6X/3 weeks
2 Kim 201019) PA : Root Bark of Ulmus davidiana Planch IJ: Normal saline ST35, EX-LE4, EX-LE2, Ashi point 12X/6 weeks
3 Park 200620) PA : Homnis placenta (0.1ml each point) AC: Stainless steel needle (0.30*40mm) BL24, EX-LE4, ST35, GB34, SP10, ST34, Ashi point 6~9X/3 weeks
4 Yu 200221) PA: Cnidium officinale (2ml) IJ: Triamcinolone
+lidocaine
EX-LE2, EX-LE4, ST35 18X/4 weeks
5 Sun 200922) PA: Compound Angelica (0.5~1ml each point) AC: Stainless steel needle (0.25*40mm)
M: Medicine (celecoxib 0.2g bid)
ST34, SP10, SP9, GB34 12X/4 weeks
6 Cai 201323) PA: Salvia miltiorrhiza (3~5ml)
+IA: sodium hyaluronate
IA : Sodium hyaluronate SP10, ST34, GB34, SP9, EX-LE4, ST35 5X/5 weeks
7 Hua 201424) PA: Shuxuening 舒血宁 2ml)
+lidocaine (0.5ml)
+IV: 鹿瓜多肽 (16mg) +血栓通 (150mg*2)
IV: 鹿瓜多肽 (16mg) +血栓通 (150mg*2) Ashi point (around the knee) 4X/2 weeks
8 Gao 201825) PA: Salvia miltiorrhiza (1ml)
+M: Celecoxib (0.2g)
+IA: Sodium hyaluronate (2ml)
M: Celecoxib (0.2g)
+IA: Sodium hyaluronate (2ml)
SP10, BL17, ST36, GB39, GB33, KI3 30X/10 weeks
9 Ye 201126) PA: Angelica (2ml)
+WN: Stainless steel needle (0.30*40mm)
+Moxibustion
M: Diclofenac sodium (25mg tid)
+WN: Stainless steel needle (0.30*40mm)
+Moxibustion
PA: ST35, ST34, ST36, GB34
WN: EX-LE4, ST35, EX-LE2, ST34, SP10, LR8, LR7, GB33, SP9, GB34, ST36
28X/4 weeks
10 Zhang 201427) PA : Salvia miltiorrhiza (2ml)
+AC: Stainless steel needle (0.30*40mm)
AC: Stainless steel needle (0.30*40mm) PA: SP10, GB34
AC: EX-LE4, ST35, SP10, ST34, GB34, SP9
6X/2 weeks
11 Liu 201528) PA: Salvia miltiorrhiza (2ml)
+EA: Stainless steel needle (0.30*40mm)
EA: Stainless steel needle (0.30*40mm) PA: GB34, BL11
EA: GB34, ST34, SP10, EX-LE4, ST35, SP9
18X/6 weeks
12 Li 201629) PA: Angelica (2ml) +placenta (2ml)
+HM: Dokwhalgisaengwhan
HM: Dokwhalgisaengwhan ST36, SP10, BL40, GB34, SP9 7X/2 weeks
13 Conrad 201930) BV: Honey bee venom (HBV) biotherapy (100 μg each) IJ: Histamine phosphate dermal injection (2.75 μg each) Knee top, EX-LE4, ST35, ST34, BL40, BL19, BL21, BL24, BL25, BL27 15X/15 weeks
14 Lee 200331) BV: Dry bee venom dissolved in saline (3000:1/0.05–0.25cc) AC: Stainless steel needle (0.25*30mm) BV: EX-LE4, ST35, Ashi point
AC: EX-LE2, EX-LE4, ST35, ST36, LR3, ST34, SP10
NR/NR
15 Ryu 200432) BV: Dry bee venom dissolved in saline (0.005%/0.01–0.4cc) AC: Stainless steel needle (0.25*50mm) BV: IA, Ashi point
AC: EX-LE2, ST35, EX-LE4, ST34, ST36, GB34
12X/4 weeks
16 An 200633) BV: Dry bee venom dissolved in saline (3000:11/0.05–0.25cc) AC: Stainless steel needle (0.25*40mm) BV: IA, Ashi point
AC: EX-LE2, EX-LE4, ST35, GB34, LR3, ST34, SP10
NR/NR
17 Yang 201334) 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
10X/5 weeks
18 Kwon 200135) 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 8X/4 weeks
19 Li 201436) BV: Pick live bees AC: Stainless steel needle (0.30*40mm) BV: Ashi point, EX-LE4, ST35, GB34
AC: Ashi point, EX-LE4, ST35, GB34, SP10, SP9
5X/2 weeks
20 Liu 201437) BV: Pick live bees ET: Electrotherapy Ashi point, EX-LE4, ST35, SP10, ST36, ST32, ST34, BL40, GB34, SP9, LR8, BL24 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.

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 ST34 1 LR3, BL11, BL17, BL19, BL21, BL25, BL27, GB33, GB39, KI1, ST32
8 Ashi point
5 ST36
SP9

Total 23 acupoints

Appendices

Appendix

Pain VAS

jkm-41-1-55f3.gif

WOMAC total

jkm-41-1-55f4.gif

EQ-5D

jkm-41-1-55f5.gif

Effective rate

jkm-41-1-55f6.gif

Pain VAS

jkm-41-1-55f7.gif

WOMAC total

jkm-41-1-55f8.gif

Effective rate

jkm-41-1-55f9.gif

Pain VAS

jkm-41-1-55f10.gif

WOMAC total

jkm-41-1-55f11.gif

Effective rate

jkm-41-1-55f12.gif

VAS

jkm-41-1-55f13.gif

WOMAC total

jkm-41-1-55f14.gif

Effective rate

jkm-41-1-55f15.gif

Effective rate

jkm-41-1-55f16.gif

Pain VAS (walking)

jkm-41-1-55f17.gif

Pain VAS (resting)

jkm-41-1-55f18.gif

WOMAC pain

jkm-41-1-55f19.gif

WOMAC function

jkm-41-1-55f20.gif

VAS

jkm-41-1-55f21.gif

WOMAC total

jkm-41-1-55f22.gif

WOMAC pain

jkm-41-1-55f23.gif

WOMAC stiffness

jkm-41-1-55f24.gif

WOMAC function

jkm-41-1-55f25.gif

SF-36

jkm-41-1-55f26.gif

Effective rate

jkm-41-1-55f27.gif

Effective rate

jkm-41-1-55f28.gif

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47 Gu JH, Kim ES, Park YC, Jung IC, Lee EJ. A Systematic Review of Bee Venom Acupuncture for Knee Osteoarthritis. Journal of Korean Medicine Rehabilitation. 2017; 27:3. 47–60.
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48 Park J, Lee H, Shin BC, Lee MS, Kim B, Kim JI. Pharmacopuncture in Korea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Evid Based Complement Alternat Med. 2016; 2016:4683121.
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49 Kim DY. Effect of testudinis carapax on expression of cyclooxygenase-2 in L929 fibroblast cell line. Kyunghee University. 2003.


50 Lim JH, Park YM, Jeong HJ, Seo EW. Effect of Cnidium officinale Mixture on Recovery Capability of DNCB-induced Allergic Contact Dermatitis in Rat. Journal of Experimental & Biomedical Sciences. 2011; 17:1. 47–53.


51 FANG L, Xiao XF, Liu CX, HE X. Recent advance in studies on Angelica sinensis. Chinese Herbal Medicines. 2012; 4:1. 12–25.


52 Park KB, Baek ST, Lee SD, Kim KH, Kim KS. The Effect of Homnis Placenta Herbal Acupuncture on Reducing Expression of LPS-induced Arthritis Model as an Anti-inflammatory Agent. Journal of Acupuncture Research. 2006; 23:6. 103–115.


53 Huang GY. The effect of Shuxuening intra-articular injection in the treatment of osteoarthritis and its influence on cyto-kines in synovial fluid. Chinese Journal of Primary Medicine and Pharmacy. 2014; 15. 2319–2320.


54 Kil SY, Kim KH, Lee SD, Kim KS, Yoon JH. Suppressive effects of a water extract of Ulmus davidiana Planch (Ulmaceae) on collagen-induced arthritis in mice. Journal of Acupuncture Research. 2005; 22:2. 43–53.


55 Kocyigit A, Guler EM, Kaleli S. Anti-inflammatory and antioxidative properties of honey bee venom on Freund’s Complete Adjuvant-induced arthritis model in rats. Tocxicon. 2019; 161:4–11.
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56 Han SH, Youn YS, Kim SS, Chung WS. A Case Report on Bee Venom Acupuncture for Patient with Osteo-Arthritis of Knee Joint, Diabetic Mellitus, and No Response for Steroid Injection. The Journal of Korea CHUNA Manual Medicine for Spine & Nerves. 2003; 4:1. 17–28.


57 Baek SH, Kim SY. Pharmacologic treatment of osteoarthritis. Journal of the Korean Medical Association. 2013; 6:12. 1123–1131.
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58 Witt C, Brinkhaus B, Jena S, Linde K, Streng A, Wagenpfeil S, et al. Acupuncture in Patients With Osteoarthritis of the Knee: A Randomized Trial. Lancet. 2005; 366:9480. 136–143.
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59 The Korean Acupuncture & Moxibustion Medicine Society. Acupunctural Clinical Guideline for Knee Pain. The Korean Acupuncture & Moxibustion Medicine Society.[serial online];2013. [cited 2013 Aug 9]. 1:1. Available from: http://kamms.org/html_2016/kamms_guide/sub04_03.html


60 Rezasoltani Z, Taheri M, Mofrad MK, Mohajeran SA. Periarticular Dextrose Prolotherapy Instead of Intra-Articular Injection for Pain and Functional Improvement in Knee Osteoarthritis. J Pain Res. 2017; 10:1179–1187.
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61 Noh SS, Lee JJ, Hwang SM, Lim SY, Chung IY, Choi YR. Efficacy of Intra-articular Sodium Hyaluronate in Patients with Osteoarthritis of the Knee. The Korean Journal of Pain. 2004; 17:2. 170–174.
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62 Jung CY, Kim EJ, Hwang MS, CHo HS, Kim KH, Lee SD, et al. The Research of Pain and Functional Disability Assessment Scales for Knee Joint Disease. Journal of Acupuncture Research. 2010; 27:2. 123–142.


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