Efficacy and Safety of Pharmacopuncture and Bee venom Acupuncture for Knee Osteoarthritis: A systematic review and meta-analysis

Yeon Jae Lee; Hyo Rim Jo; Seon Hye Kim; Won Suk Sung; Eun Jung Kim; Lee, Yeon Jae; Jo, Hyo Rim; Kim, Seon Hye; Sung, Won Suk; Kim, Eun Jung

doi:10.13048/jkm.20005

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

Original Article

The Journal of Korean Medicine 2020; 41(1): 55-83.

Published online: March 9, 2020

DOI: https://doi.org/10.13048/jkm.20005

Efficacy and Safety of Pharmacopuncture and Bee venom Acupuncture for Knee Osteoarthritis: A systematic review and meta-analysis

Yeon Jae Lee¹

, Hyo Rim Jo²

, Seon Hye Kim²

, Won Suk Sung²

, Eun Jung Kim²^{, *}

¹College of Korean Medicine, Dongguk University

²Dep. of Acupuncture & Moxibustion Medicine, Dongguk University Bundang Oriental Hospital

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: +82-31-710-3751, Fax: +82-31-710-3780, E-mail: hanijjung@naver.com

Received February 13, 2020 Revised February 27, 2020 Accepted February 27, 2020

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.

Keywords: Knee osteoarthritis (knee OA), Pharmacopuncture, Bee venom Acupuncture, Systematic review, Meta-analysis

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

Fig. 2

Risk of bias summary and graph

(+), Low risk of bias; (−), High risk of bias; (?), Unclear of bias.

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)	SF-MPQ VAS PPI sensory affective WOMAC EQ-5D	E>C (p=0.000) E>C (p=0.049) E>C (p=0.004) E=C E>C (p=0.004) 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)	VAS WOMAC KHAQ SF-36	E=C E=C E=C 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)	Lysholm score Nine point scale	E=C 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)	Effective rate Intra bony pressure	E>C (p<0.05) 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)	Effective rate ISOA Serum NO levels	E>C1 (p=0.005) E>C2 (p=0.031) E=C1=C2 (Statistics not mentioned) 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)	VAS Lysholm score Effective rate	E>C (p<0.01) E>C (p<0.05) 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)	VAS WOMAC	E>C (p<0.05) 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)	VAS WOMAC Lequesne scale Inflammatory cells and CRP levels in synovial fluid	E>C (p<0.05) E>C (p<0.05) E>C (p<0.05) 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)	Effective rate	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)	VAS WOMAC Knee circumstance score	E>C (p=0.043) E>C (p=0.045) 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)	VAS Lysholm score Effective rate	E>C (p<0.01) E>C (p<0.01) 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)	Effective rate	E>C (p<0.05)	NR	PA is effective in treating knee osteoarthritis
13	Conrad 201930) USA	367	E: BV (234)	C: Placebo (133)	WOMAC pain fuction VAS PGA, PhGA	E>C (p=0.001) E>C (p=0.0046) E>C (p<=0.0012) 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)	Effective rate Nine-point scale Grade of clinical symptoms	E>C (Statistics not mentioned) E>C (p=0.008) E>C (p=0.04)	NR	BV treatment was more effective than AC
15	Ryu 200432) Korea	51	E: BV (26)	C: AC (25)	VAS WOMAC total pain stiffness function Lequesne’s index	E>C (p=0.003) E>C (p=0.004) E>C (p=0.003) E>C (p=0.195) E>C (p=0.005) 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)	WOMAC	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)	VAS WOMAC pain stiffness function SF-36	E>C (p=0.001) E>C (p=0.001) E>C (p=0.000) E>C (p=0.007) 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)	Subjective Pain Relief Score (Excellent, good, fair, poor) Infrared Thermography	E>C (p<0.01) 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)	HSS total pain function muscle strength mobility total TCM syndrome score	E>C (p=0.093) E>C (p=0.046) E=C (p=0.063) E=C (p=0.096) E=C (p=0.257) 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)	Effective rate Remarkable effective rate	E>C (p<0.05) 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	1
5	ST36
	SP9

Total 23 acupoints

Appendices

Appendix

Pain VAS

WOMAC total

EQ-5D

Effective rate

Pain VAS

WOMAC total

Effective rate

Pain VAS

WOMAC total

Effective rate

VAS

WOMAC total

Effective rate

Pain VAS (walking)

Pain VAS (resting)

WOMAC pain

WOMAC function

VAS

WOMAC total

WOMAC pain

WOMAC stiffness

WOMAC function

SF-36

Effective rate

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