Treatment of knee osteoarthritis with acupuncture combined with Chinese herbal medicine: a systematic review and meta-analysis
Original Article

Treatment of knee osteoarthritis with acupuncture combined with Chinese herbal medicine: a systematic review and meta-analysis

Fan Yang, Ying Chen, Zhihui Lu, Wanyi Xie, Shan Yan, Jiao Yang, Yunhai Li

Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China

Contributions: (I) Conception and design: F Yang, Y Li; (II) Administrative support: Y Li; (III) Provision of study materials or patients: F Yang, Y Chen, Z Lu; (IV) Collection and assembly of data: F Yang, W Xie, S Yan; (V) Data analysis and interpretation: F Yang, J Yang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Fan Yang; Yunhai Li. Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan 430061, China. Email: 875350152@qq.com; 155350975@qq.com.

Background: Many studies have demonstrated that acupuncture combined with Chinese herbal medicine (CHM) effectively treats knee osteoarthritis (KOA), with few side effects. However, few systematic reviews have offered evidence-based support. Here we conducted a meta-analysis on the combination of acupuncture with CHM in treating KOA.

Methods: Databases including CNKI, Wanfang, VIP, PubMed, EMBASE, and Cochrane library were systematically searched for articles on the treatment of KOA by acupuncture combined with CHM from the establishment of the database to May 2021. Three researchers independently searched, screened, extracted, and included articles that met the inclusion standards. The primary outcome measure was overall response rate (ORR), and the secondary outcome measures included Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Lysholm score. ORR was a binary variable, while other indicators were continuous variables. The quality of literature was assessed with a modified Jadad scale. The RevMan 5.3 software provided by the Cochrane Collaboration was used for statistical analysis.

Results: Thirty-three randomized controlled trials involving 3,954 patients were included. Meta-analysis showed that ORR [odds ratio (OR) =5.41; 95% confidence interval (CI): (4.38, 6.68); P<0.00001], VAS score [mean difference (MD) =−1.86; 95% CI: (−2.44, −1.29); P<0.00001], WOMAC score [MD =−13.05; 95% CI: (−21.70, −4.41); P=0.003], and Lysholm score [MD =10.47; 95% CI: (5.21, 15.72); P<0.0001] in the combination group were significantly superior to those in the control group.

Discussion: Compared with acupuncture alone or CHM/Western drug alone, acupuncture combined with CHM can effectively alleviate knee pain, improve knee function, and increase the quality of life. Thus, this combination can be used as a conservative treatment for KOA. However, due to the small number of high-quality articles and possible biases in our analysis, our conclusions need to be further verified in more and higher-quality studies.

Keywords: Knee osteoarthritis (KOA); acupuncture; traditional Chinese medicine; randomized controlled trial; meta analysis


Submitted Aug 04, 2021. Accepted for publication Oct 19, 2021.

doi: 10.21037/apm-21-2565


Introduction

Osteoarthritis (OA) is a chronic degenerative disease that affects approximately 10% of men and 18% of women worldwide. The incidence of OA is increasing annually, along with increased aging. About 60–65% of people over 60 years of age suffer from symptomatic OA, of which 80% of patients present with symptoms including joint stiffness and limited range of motion, which seriously affects the quality of life of the victims (1,2). Even worse, an increasing proportion of young adults have also suffered from OA. OA is a heterogeneous disease caused by multiple factors and characterized by progressive decomposition of articular cartilage. It is commonly believed that knee osteoarthritis (KOA) results from a result of multiple pathogenic factors, such as age, sex, body quality, trauma and genetics, abnormal mechanical load, insufficient nutrition supply and genetic inducement, as well as metabolic factors and infrapatellar fat pad. and is characterized by joint pain and dysfunction with progressive intraarticular and subchondral bone injury, synovitis, osteophyte formation and reduced joint cava. As the prevalence of OA is rising, the treatment requirements on this disease also increase (3).

The current treatments of KOA mainly include non-steroidal anti-inflammatory drugs (NSAIDs), chondroitin, hyaluronic acid, surgical therapy, traditional Chinese medicine, acupuncture/massage, and exercise therapy. Weight reduction and muscle strength training around the knee joint may also help. Among them, the combination of acupuncture with Chinese herbal medicine (CHM) is highly effective, with few side effects. Also, it is simple and affordable (4,5).

A previous meta-analysis had investigated the efficacy and safety of this strategy, but with low literature quality, small sample size, and a limited number of response assessment indicators (6). As more relevant articles have been published in recent years, an updated meta-analysis with high-quality articles is warranted to provide accurate, reliable, and multifaceted evidence to evaluate the clinical efficacy of the combination in treating KOA. We present the following article in accordance with the PRISMA reporting checklist (available at https://dx.doi.org/10.21037/apm-21-2565).


Methods

Literature search strategy

Computer-based search

A computer-based search was performed by three researchers.

Databases

The Chinese databases included CNKI, Wanfang, VIP, and China Biomedical Literature (CBM) database; and English databases included PubMed, EMBASE, and Cochrane Library.

Search words

The search words included, “acupuncture”, “electroacupuncture”, “traditional Chinese medicine treatment”, “knee osteoarthritis”, “osteoarthritis of the knee”, “knee joint osteoarthritis”, and “KOA”, in Chinese and English, respectively.

Time period

The period between searches was from the month the databases were created to May 2021.

Search strategy

The search method of combining subject terms with free-text synonyms was used. An example of searching in PubMed is shown in Table 1.

Table 1

The search strategy for PubMed

No. Search term Search scope
#1 Acupuncture [Title/Abstract]
#2 Electroacupuncture [Title/Abstract]
#3 Traditional Chinese medicine treatment [Title/Abstract]
#4 #1 OR #2 OR #3
#5 Knee osteoarthritis [Title/Abstract]
#6 Osteoarthritis of the knee [Title/Abstract]
#7 Knee joint osteoarthritis [Title/Abstract]
#8 KOA [Title/Abstract]
#9 #5 OR #6 OR #7 OR #8
#10 #4 AND #9

Inclusion and exclusion criteria

Inclusion criteria

The inclusion criteria included: (I) the included patients met the diagnostic criteria of KOA; (II) published randomized controlled trials, with clearly-defined baseline data; (III) whether blinding is used or not; (IV) the combination group included patients who had received the combination of acupuncture with CHM alone, while the control group included patients who had undergone other treatment methods different from the combination of acupuncture and CHM; (V) the outcome measures included any of the following indicators: overall response rate (ORR), Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Lysholm score. All the outcomes measures were reliable.

Exclusion criteria

The exclusion criteria included: (I) articles with poorly-defined diagnostic criteria, efficacy indicators, and/or descriptions; (II) articles with incorrect trial design or statistical methods; (III) reviews, dissertations, conference proceedings, and nursing records; (IV) basic experiments; (V) case reports and anecdotal evidence; (VI) expert experience; (VII) unpublished articles or overlapping publications; (VIII) articles with obvious errors or incomplete data; (IX) the original full-text is not available; and (X) literature where acupuncture and CHM are used as adjuvant therapy.

Data extraction

The search, inclusion, and exclusion of the literature were performed by two well-trained and qualified medical practitioners who had clinical experience in rheumatology and acupuncture, and the initial articles were screened after verification. The data extraction of the initial articles was then performed independently by two investigators and checked by a third investigator. In case of disagreement, the third investigator and the principal investigator negotiated to make a final decision. If there were missing data in the literature, the corresponding author was contacted via email or phone call to obtain such data. The extracted data mainly included: (I) basic information about the included articles: first author and year of publication, etc.; (II) information about the included subjects: number and ages of subjects in the combination group and the control groups, etc.; (III) study designs: types of design, interventions, and details, etc.; and (IV) outcome indicators and outcome measures: ORR, WOMAC score, VAS score, and Lysholm knee function score, etc.

Assessment of literature quality

The bias risk of the included studies was assessed using the Cochrane Bias Risk tool from the Handbook of the Cochrane Collaboration for Systematic Intervention Reviews, version 5.1.0 (https://www.cochrane.org/), which assesses the following seven domains: (I) allocation of the randomization sequence (selection bias); (II) allocation concealment (selection bias); (III) blinding of the participants and the team involved (performance bias); (IV) blinding of outcome evaluators (detection bias); (V) incomplete outcomes (attrition bias); (VI) report of selective outcome (publication bias); and (VII) other sources of bias.

The methodological quality of the literature was evaluated according to the Jadad score by two independent researchers with a valid Good Clinical Practice (GCP) certificate, and checked by a third investigator. In case of disagreement, the third investigator and the principal investigator negotiated to make a final decision. Points were awarded as follows: (I) randomization: 1 point was given if randomization was mentioned; additional 1 point was given if appropriate randomization was used; (II) double blinding: 1 point was given if double blinding was mentioned; additional 1 point was given if the method of double blinding was appropriate; and (III) withdrawals and dropouts: 1 point was given for a clear description of withdrawals and dropouts. Articles were rated as low-quality if scored 0–2 points, and as high-quality if scored 3–5 points.

Outcome measures

The primary outcome measure was ORR, and the secondary outcome measures included VAS score, WOMAC score, and Lysholm score.

Statistical analysis

Meta-analysis was performed using RevMan software (version 5.3; Cochrane Collaboration). Both fixed- and random-effects models were used. Heterogeneity was quantified by I2 statistics. I2<50% suggested no heterogeneity, and the data were pooled using the fixed-effects model; I2>50% suggested the presence of heterogeneity among the studies, and the random-effects meta-analysis was employed. If more than 10 studies were included for a specific outcome measure, the presence of morbidity bias was analyzed using inverted funnel plots. The odds ratio (OR) was used as the effect measure for binary variables, and the mean difference (MD) was used for measures with the same unit and measurement method. A 95% confidence interval (CI) was given, and a P value of <0.05 was considered statistically significant.


Results

Literature search and screening

A flow chart of the study selection process is shown in Figure 1.

Figure 1 Literature search & screening flowchart.

Basic features of the included studies

The basic features of the included 33 studies are summarized in Table 2. There is no English literature.

Table 2

Information of the included studies

Articles Group Pooled sample size (n) Gender (male/female) Age (years) Disease course (years) Interventions Treatment course Response evaluation criteria
Mo LL, 2013 (7) Combination group 320 160 (63/97) 72.40±3.50 4.50±2.52 Acupuncture + CHM 2 months VAS score, LKSS score, Lysholm score, response rate
Control group 160 (76/84) 71.50±3.25 4.60±2.60 Acupuncture
Zhang BY, 2017 (8) Combination group 80 40 (9/31) 53±7 2.2 Acupuncture + CHM 4 weeks ORR
Control group 40 (12/28) 52±9 2.4 CHM
Guo PF, 2010 (9) Combination group 93 55 (16/39) 38–65 15 days–11 years Acupuncture + CHM 25 days ORR
Control group 38 (12/26) 40–68 16 days–14 years Indomethacin
Chen HL, 2011 (10) Combination group 92 48 (19/29) 45–71 20 days–15 years Acupuncture + CHM 25 days ORR
Control group 44 (16/28) 41–76 18 days–13 years Acupuncture
Li HT, 2020 (11) Combination group 80 40 (12/28) 55±5 7.24±1.46 Acupuncture + CHM 8 weeks ORR, WOMAC score, and VAS score
Control group 40 (15/25) 53±7 7.69±2.01 CHM
Sun J, 2014 (12) Combination group 60 (16/44) 30 56.85 23.7 months Acupuncture + CHM 4 weeks Recovery of joint function and WOMAC score
Control group 30 Acupuncture
Zhang H, 2015 (13) Combination group 200 100 (41/59) 58.58±10.57 Acupuncture + CHM 10 days ORR
Control group 100 (39/61) 59.21±10.54 CHM
Ma X, 2009 (14) Combination group 140 70 (–/–) CHM + acupuncture + topical washing + ultrashort wave therapy + computerized medium frequency therapy + direct current induction therapy 15 days ORR
Control group 70 (–/–) Ibuprofen extended-release capsules
Feng Z, 2014 (15) Combination group 100 50 (22/28) 56±9.8 CHM + acupuncture + topical application 14 days ORR and HSS
Control group 50 (19/31) 54±10.1 CHM
Liu XM, 2016 (16) Combination group 80 (42/38) 40 55±6.7 1.2±0.5 CHM + acupuncture + massage 3 weeks ORR
Control group 40 Nobumetone capsules 6 weeks
Gui HQ, 2019 (17) Combination group 100 50 (32/18) 53.89±2.56 4.01±0.45 Acupuncture + CHM 10 days ORR, functional improvement time, inflammatory factors, and joint function score
Control group 50 (31/19) 53.25±2.24 4.03±0.42 CHM
Ma YH, 2017 (18) Combination group 81 (30/51) 45 49–75 Acupuncture + CHM 28 days ORR
Control group 36 52–69 CHM
Chen LS, 2017 (19) Combination group 168 84 (35/49) 54.2 7.3 Acupuncture + CHM 5 weeks ORR
Control group 84 (38/46) 53.8 7.1 Diclofenac sodium dual release enteric coated capsules (orally administered) + diclofenac sodium (topically applied) 30 days
Ou ZL, 2017 (20) Combination group 92 46 (19/27) 61.34±3.46 3.56±1.03 Acupuncture + CHM 4 weeks ORR, joint swelling index, joint pressure pain index, and ESR
Control group 46 (17/29) 60.57±3.71 3.60±1.08 Compound ossotide injection + CHM decoction
Ma P, 2011 (21) Combination group 166 83 (42/41) 51.2 7.5 months CHM + acupuncture + ibuprofen extended-release capsules 30 days ORR
Control group 83 (44/39) 52.5 7.2 months Ibuprofen extended-release capsules
Ge XT, 2009 (22) Combination group 200 150 (49/101) 55.8 (39/ 85) 30 days–12 years CHM + acupuncture + medium-frequency electrotherapy 60 days ORR
Control group 50 (25/25) 41–82 29 days–13 years Diclofanac sodium sustained-release tablets + huoxue zhitong capsules
Sun ZJ, 2013 (23) Combination group 280 140 CHM + acupuncture + massage 2 weeks ORR and pain scale scores
Control group 140 Nobumetone capsules 3 weeks
Zhu LY, 2020 (24) Combination group 60 30 (15/15) 61.50±6.85 1.29±0.26 CHM + acupuncture/massage + meloxicam + sodium hyaluronate 4 weeks ORR and Lysholm score
Control group 30 (14/16) 62.11±7.11 1.34±0.25 Oral meloxicam capsule + intra-articular injection of sodium hyaluronate
Wang RJ, 2019 (25) Combination group 100 50 (30/20) 49.7±5.2 8.3±4.3 CHM + acupuncture + sparrow-pecking moxibustion ORR, degree of knee joint motion, and knee pain score
Control group 50 (27/23) 50.8±6.2 9.3±3.3 CHM
Zhu JH, 2010 (26) Combination group 100 50 65.13 6 months–10 years Acupuncture + CHM + functional rehabilitation 4 weeks Lysholm score
Control group 50 Acupuncture + CHM
Lai ZS, 2011 (27) Combination group 40 20 56.2±2.5 3.1 CHM (orally and topically) + acupuncture 4 weeks ORR
Control group 20 Intra-articular injection of sodium hyaluronate
Li ZH, 2010 (28) Combination group 100 50 (13/37) 48–75 3 months–5 years Acupuncture + CHM 1 month ORR
Control group 50 (14/36) 47–72 4 months–4 years Intra-articular injection of sodium hyaluronate
Wu DP, 2008 (29) Combination group 60 30 (14/16) 64.1 5.7 Acupuncture + CHM 1 month ORR
Control group 30 (13/17) 61.8 5.5 Diclofenac
Sun Y, 2013 (30) Combination group 120 (69/51) 40 50.4 3.4 CHM + acupuncture + sparrow-pecking moxibustion 2 months ORR
Control group 40 CHM
Two control groups 40 Acupuncture
Yin QD, 2009 (31) Combination group 120 60 (31/29) 57 15 CHM + acupuncture + topical application 4 weeks ORR and VAS
Control group 60 (32/28) 56 16 Topical application with diclofenac-diethylamine gel
Ding WM, 2013 (32) Combination group 50 (26/24) 25 51.46±13.26 CHM + acupuncture + topical application (topical) ORR
Control group 25 Ibuprofen
Qiu YQ, 2013 (33) Combination group 146 (84/62) 112 67.3±3.1 CHM (oral + topical) + acupuncture/massage 6 months ORR, knee function score, pain level, and functional recovery time
Control group 34 Glucosamine hydrochloride capsules + diclofenac (topical)
Jiao FD, 2017 (34) Combination group 140 70 (33/37) 58.8±1.6 5.1±0.7 CHM + acupuncture/massage + teng therapy (heat spreading therapy) + akupotomye 1.5 months ORR and WOMAC
Control group 70 (34/36) 58.7±1.8 5.2±0.6 Intra-articular injection of sodium hyaluronate + oral administration of glucosamine hydrochloride
Huang XW, 2018 (35) Combination group 80 40 (17/23) 57.3±7.61 CHM + acupuncture + massage 2 months ORR + joint pressure and pain sensation score, joint swelling score, and arthritis index
Control group 40 (14/24) 58.1±7.62 Acupuncture + massage
Bai Y, 2017 (36) Combination group 104 52 (27/25) 63.2±5.1 7.1±3.2 Intra-articular injection of sodium hyaluronate + CHM + acupuncture 1 month ORR
Control group 52 (23/29) 65.5±4.7 6.3±3.1 Sodium hyaluronate
Yu ZX, 2017 (37) Combination group 112 56 (30/26) 59.7±7.2 22.7±11.9 CHM + acupuncture + massage ORR
Control group 56 (32/24) 58.2±6.5 23.5±12.5 Acupuncture + massage
Chen SY, 2015 (38) Combination group 210 120 (74/46) 62 9.8 CHM decoctions, fumigation and soaking therapy, massage, small akupotomye, acupuncture, symptomatic pain relief, and intra-articular injection of sodium hyaluronate ORR
Control group 90 (51/39) 61.50±6.85 10.1 Intra-articular injection of sodium hyaluronate + oral administration of NSAIDs
Niu GY, 2011 (39) Combination group 80 (33/47) 40 51.2 4.6 Acupuncture + CHM 30 days ORR
Control group 40 Meloxicam

CHM, Chinese herbal medicine; NSAID, non-steroidal anti-inflammatory drugs; VAS, Visual Analogue Scale; LKSS, Lysholm knee score; ORR, overall response rate; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; HSS, hospital for special surgery knee score; ESR, erythrocyte sedimentation rate.

Quality of the included articles

The included articles’ biases were assessed using the relevant tools in the Cochrane Handbook for Systematic Reviews of Interventions. A bar graph showing the assessment results is shown in Figure 2, and a pooled graph is shown in Figure 3.

Figure 2 Bar chart for bias risks of the included studies.
Figure 3 Bias risk assessment of the included studies. +, low risk; ?, unknown; −, high-risk.

Outcome measures

ORR

ORR was calculated in 31 articles (Figure 4). The heterogeneity among studies was low (P=0.03; I2=36%), so the fixed-effects model was used [OR =5.41 and its 95% CI was (4.38, 6.68); Z=15.66; P<0.00001]. Meta-analysis showed that the combination group had a higher ORR than the control group. In particular, acupuncture combined with orally administered CHM had significantly higher clinical efficacy compared with other treatment methods. The funnel plot is shown in Figure 5. The plot shows only slight asymmetry, indicating a possible minor publication bias.

Figure 4 Forest plot of the meta-analysis of ORR. ORR, overall response rate.
Figure 5 Funnel plot of the meta-analysis of ORR. ORR, overall response rate; OR, odds ratio; SE, standard error.

VAS score after treatment

VAS score was mentioned in 3 articles (Figure 6). The heterogeneity among studies was high (P<0.00001; I2=98%), so the random-effects model was used [MD =−1.86 and its 95% CI was (−2.44, −1.29); Z=6.37; P<0.00001]. Meta-analysis showed that the combination group had a larger decrease in VAS score after treatment than the control group. In particular, acupuncture combined with orally administered CHM had significantly higher VAS score improvement than other treatment methods. Thus, the combination could dramatically alleviate the pain symptoms.

Figure 6 Forest plot of meta-analysis of VAS score after treatment. VAS, Visual Analogue Scale.

WOMAC score after treatment

WOMAC score was mentioned in 3 articles (Figure 7). The heterogeneity among studies was high (P<0.00001; I2=100%), so the random-effects model was used [MD =−13.05 and its 95% CI was (−21.70, −4.41); Z=2.96; P=0.003]. Meta-analysis showed that the combination group had a larger decrease in WOMAC score after treatment than the control group. In particular, acupuncture combined with orally administered CHM had a significantly higher decrease in WOMAC score compared with other treatment methods. Thus, the combination could effectively relieve knee pain and stiffness in KOA patients and improve their daily living difficulties.

Figure 7 Forest plot of meta-analysis of WOMAC score after treatment. WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Lysholm score after treatment

Lysholm score was mentioned in 2 articles (Figure 8). The heterogeneity among studies was high (P=0.007; I2=86%), so the random-effects model was used [MD =10.47 and its 95% CI was (5.21, 15.72); Z=3.91; P<0.0001]. Meta-analysis showed that the combination group had a higher Lysholm score after treatment than the control group. In particular, acupuncture combined with orally administered CHM significantly increased the Lysholm score compared with other treatment methods. Thus, the combination could effectively relieve knee pain, stiffness, and swelling in KOA patients, and improve the quality of life.

Figure 8 Forest plot of meta-analysis of Lysholm score after treatment.

Adverse reactions

Adverse reactions were mentioned in two studies (Figure 9). In one study, the incidence of adverse reactions was 1.92% (mild swelling of the lower extremities in one case) and 3.85% (diarrhea in one case and dizziness in one case), respectively, in the control group and the combination group, showing no significant difference (P>0.05). In another study, two patients in the combination group experienced mild gastrointestinal discomfort and abdominal distension, which disappeared after stopping the CHM. Three patients showed gastrointestinal reactions in the control group, manifested as nausea, vomiting, abdominal pain, and constipation, which resolved after stopping the CHM. There were no significant changes in the findings of routine blood tests, routine urine tests, and liver/kidney function tests before and after treatment in both groups.

Figure 9 Forest plot of adverse reactions.

Discussion

KOA is a common degenerative disease of the knee joint, with the main symptoms being knee stiffness, pain, and movement disorders. Currently, the commonly used Western medical treatments, including Western drugs or surgery, still cannot cure KOA and are often associated with adverse effects (40). Therefore, the role of TCM in treating KOA has been increasingly recognized, particularly the combination of acupuncture with orally administered CHM. The clinical efficacy of acupuncture has long been demonstrated. When used in combination with liver- and kidney-tonifying drugs, wind-, cold-, and dampness-dispelling drugs, and blood circulation-activating drugs, acupuncture can alleviate KOA and reduce its recurrence. It also helps increase the patient’s quality of life and improve the economic/psychological burden of patients and their families.

The acupuncture points mentioned in the literature included neixiyan, waixiyan, zusanli, xuehai, liangqiu, yinlingquan, yanglingquan, weizhong, and ashi point, which are around the knee joint. Acupuncture at these points helps alleviate knee pain and regulate qi and blood. Acupuncture can enhance muscle strength, adjust soft tissue tension around the knee, improve joint stress, eliminate swelling and relieve pain. And promote local blood circulation, accelerate metabolism, benefit the absorption of inflammatory substances in the joint, enable the damaged tissue to repair, relieve the resting pain of the knee joint, swelling, pain from up and down stairs, stiffness and the improvement of joint mobility. The TCM orally administered Radix Angelicae Pubescentis, parasite scurrula, Radix Cyathulae, Poria, Radix Saposhnikoviae, Rhizoma Ligustici Chuanxiong, Radix Codonopsis, Radix Angelicae Sinensis, Radix Paeoniae Alba, Radix Rehmanniae Preparata, Radix Aconiti Preparata, and Eupolyphaga Seu Steleophaga. They were mainly liver- and kidney-tonifying drugs and blood circulation-activating drugs. It has modern pharmacological effects such as anti-inflammatory, analgesia, expanding blood vessels, improving circulation and regulating immune functions. The Chinese herbs with the actions of activating blood flow and removing blood stasis, and strengthening the muscles and bones were applied to the affected sites and irradiation by the spectrograp can promote the local absorption of medicines. Herbs with the effects of activating blood flow and removing blood stasis can ameliorate hemodynamical state, promote the microcirculation and improve the hypercoagulability to relieve blood stasis. Moreover, the herbs effective to nourish the kidney and strengthen effective to bones, activate blood flow and remove blood stasis can inhibit chrondral degeneration and promote the auto-reparation of the cartilagines TCM. Thus, they can exert very well effects in treating and preventing the KOA. The combination treats the disease via both oral and topical approaches, and from local and systemic perspectives. Strengthening the tendons, bones, and joints relieves knee pain and improve the quality of life in KOA patients.

Here we systematically evaluated the efficacy of the combination in treating KOA. A meta-analysis was conducted on the retrieved studies. Data were extracted from studies without significant heterogeneity and pooled with appropriate statistical methods to draw comprehensive conclusions, which to a certain extent can yield more reliable clinical data. The results suggested that the combination could effectively increase the ORR and reduce disease recurrence. However, most of the included articles were of low quality, as they failed to strictly follow the requirements of randomized control trials (e.g., blinding), and some of them were biased. The limitations of our current analysis are summarized as follows: (I) due to insufficient relevant foreign language literature, the included articles were all small-sample, single-center randomized controlled trials published in China, which could lead to selection bias; (II) most of the studies did not mention allocation concealment and blinding, which may have some influence on the results due to the risk of bias; (III) the duration of treatment, follow-up time, and specific acupuncture points/CHM varied among different studies, so there was statistical heterogeneity; (IV) while the vast majority of randomized controlled trials focusing on the combination of acupuncture and CHM in treating KOA were included in our current analysis, only a few studies on the combinations with warm acupuncture, small needle knife, and Western medicine were retrieved for comparisons, which may result in a certain risk of bias; and (V) the three indicators, including WOMAC score, VAS score, and Lysholm score, were adopted in only a small number of studies used, and were highly heterogeneous among these studies due to differences in treatment course, interventions in control group, and grouping protocols, which undermined the reliability of the results (41,42).

Limitations and heterogeneity

The limitations of meta-analysis: 33 studies were included, mostly randomized methods and random assignment, some had only overall efficiency, too-old or self-contained efficacy criteria; most literature lacked long-term follow-up data to evaluate patients’ disease recurrence, long-term survival quality and specific adverse effects. Evaluation indicators were limited, the outcome indicators only analyzed efficiency, VAS, WOMAC score and Lysholm joint function score, such as HSS score, Inflammatory factor and adverse events were not included in the analysis. On systematic review, the article has some bias in systematic review, selection bias, incomplete or not objective; in research level, there may be publication bias, positive results are easy to publish, negative results are not acceptable, in outcome level, researchers have reporting bias, Selective reports of favorable results.

The article on the source of heterogeneity to consider the following points: acupuncture selected acupoints are different: far away Near selection points, with the evidence selection points, meridian syndrome differentiation selection points and viscera syndrome differentiation selection points, etc.

The oral CHMs selected in the literature are also different, including tonifying the liver and kidney, strengthening tendons and bones, promoting blood circulation and dredging collaterals, regulating qi and so on, which will also cause some heterogeneity.

In conclusion, the combination of acupuncture with CHM has significant efficacy in treating KOA, with remarkable therapeutic effects in improving ORR, increasing Lysholm score, and lowering VAS score and WOMAC score. With a high clinical value, it may be a preferred treatment for KOA. However, as the currently available studies still had many limitations, the conclusions of our analysis still need to be further validated in more multicenter, large-sample randomized controlled trials at home and abroad. Based on our findings, future studies may increase their quality by optimizing research protocols and increasing sample sizes. In addition, the clinical value of the combination of acupuncture with CHM in treating KOA has been demonstrated, and the underlying mechanism may be a research priority (43).


Acknowledgments

Funding: This study was supported by Hubei University of Chinese Medicine “Youth Program” (2020ZZX029) and Hubei University of Chinese Medicine Doctoral Research Start-Up Fund.


Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://dx.doi.org/10.21037/apm-21-2565

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/apm-21-2565). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


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(English Language Editor: J. Chapnick)

Cite this article as: Yang F, Chen Y, Lu Z, Xie W, Yan S, Yang J, Li Y. Treatment of knee osteoarthritis with acupuncture combined with Chinese herbal medicine: a systematic review and meta-analysis. Ann Palliat Med 2021;10(11):11430-11444. doi: 10.21037/apm-21-2565

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