Chen et al.

Journal of Orthopaedic
Journal of Orthopaedic Surgery and Research (2023) 18:921
https://doi.org/10.1186/s13018-023-04403-2 Surgery and Research

SYSTEMATIC REVIEW Open Access

Efficacy of acupuncture combined

with active exercise training in improving pain
and function of knee osteoarthritis individuals:
a systematic review and meta‑analysis
Jia Chen1†, Hong Guo2, Juanhong Pan1, Hongpeng Li3, Yongshen Wang1†, Zhixiang Liu1, Yulong Xie1 and
Song Jin2*

Abstract
Objective To conduct a systematic review and meta-analysis to investigate the clinical efficacy of acupuncture com-
bined with active exercise training in improving pain and function of knee osteoarthritis (KOA) individuals.
Data sources PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure,
Wan Fang Data, Technology Periodical Database and China Biology Medicine were searched from their inceptions
to April 5, 2023.
Review methods We analyzed trials of acupuncture combined with active exercise training for KOA. The included
studies were of high quality (Jadad ≥ 4) and RCTs. Study selection, data extraction, risk of bias and quality assessment
were independently performed by two reviewers. We performed systematic analyses based on different outcome
measures, including total efficiency rate, visual analogue scale (VAS), the Western Ontario and Mcmaster Universities
Osteoarthritis Index (WOMAC), the Lysholm Knee Scale (LKS) and range of motion (ROM). We used Review Manager
5.3 and Stata/MP 14.0 to analyze the data. And it was verified by trial sequence analysis (TSA). If I2 > 50% and p < 0.05,
we performed sensitivity analysis and subgroup analysis to find the source of heterogeneity. Publication bias
was studied by funnel plot and Egger’s test was used to verify it.
Results Full 11 high-quality studies (Jadad ≥ 4) including 774 KOA individuals were included in this review for meta-
analysis. The results showed that acupuncture combined with active exercise training (combined group) was superior
to the acupuncture group in improving the total effective rate [RR = 1.13, 95%CI (1.05, 1.22), I2 = 0%, P = 0.70], reducing
the pain level (VAS) [MD = − 0.74, 95%CI (− 1.04, − 0.43), I2 = 68%, P < 0.05], improving knee joint function (WOMAC)
[MD =  − 6.97, 95%CI (− 10.74, − 3.19), I2 = 76%, P < 0.05] and improving joint range of motion (ROM) [MD = 6.25, 95%CI
(2.37, 10.04), I2 = 0%, P = 0.71]. Similarly, the combined group showed significant improvements in the total effective
rate [RR = 1.31, 95% CI (1.18, 1.47), I2 = 48%, P = 0.10], pain (VAS) [MD = 1.42, 95% CI (− 1.85, − 1.00), I2 = 65%, P = 0.02]
and knee function (WOMAC) [MD = 7.05, 95% CI (− 11.43, − 2.66), I2 = 86%, P < 0.05] compared with the non-acupunc-
ture group.

†
Jia Chen and Yongshen Wang have contributed equally to this work and
share first authorship.
*Correspondence:
Song Jin
[email protected]
Full list of author information is available at the end of the article

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
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Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 2 of 21

Conclusion The combined effect of all studies showed significant benefits of acupuncture combined with active
exercise training in improving the total effective rate, reducing pain, promoting recovery of knee function
and expanding range of motion. However, some evaluation indicators are highly subjective and need to be further
confirmed by more objective and evidence-based high-quality RCTs in future.
Systematic Review Registration: [PROSPERO], identifier [No. CRD42023425823].
Keywords Acupuncture, Active exercise training, Knee osteoarthritis, Systematic review, Meta-analysis

Introduction exclusion criteria to further explore the efficacy of acu-

Knee osteoarthritis (KOA) is the most common degen- puncture combined with active exercise training on
erative joint disease that can cause joint pain, swelling, KOA, and whether it is better than acupuncture alone
stiffness, limited mobility and even disability [1]. The or exercise therapy alone, so as to derive a more effective
overall prevalence of primary osteoarthritis in people treatment for KOA.
over 40 years old in China is as high as 46.3% and 62.2%
in people over 60 years old [2], of which KOA accounts Methods
for more than 90% of osteoarthritis. The pathological The meta-analysis was registered on the International
manifestations of KOA are mainly cartilage fibrosis, sof- Prospective Register of Systematic Reviews (PROS-
tening, ulcer formation and deletion, subchondral osteo- PERO registration number: CRD42023425823). We also
sclerosis, osteophyte formation and synovitis [3], which reported conforming to the Preferred Reporting Items
seriously affect people’s quality of life. The prevalence of for Systematic Reviews and Meta-analyses Statement cri-
KOA is increasing year by year, and the medical cost is teria (PRISMA 2020) (Additional file 1).
huge [4], bringing a heavy burden to families and society
[5]. The etiology of KOA is complex, the pathogenesis is Search strategy
still not clear [6], and studies [7, 8] believe that the occur- Two reviewers (J.Ch. and H.G.) independently searched
rence of KOA may be related to age, gender, BMI, hered- PubMed, EMBASE, Web of science, the Cochrane
ity, occupation and other factors. At present, the main Library, China National Knowledge Infrastructure
clinical treatments include surgical treatment, non-ste- (CNKI), Technology Periodical Database (VIP), Wan
roidal drug treatment, physical therapy, exercise therapy, Fang Data and China Biology Medicine (CBM) from
etc. [8]. However, patients have a hard time reconciling the earliest available date until April 5, 2023. Follow-
the high cost of surgical treatment, and anxiety is often ing keywords and their varies were used: acupuncture
witnessed in such cases. And drug treatment often brings (AT), active exercise training (exercise), knee osteoar-
digestive side effects. One study [9] proposed that acu- thritis (KOA) and randomized controlled trials (RCTs).
puncture in the treatment of KOA could play a role in The language was restricted to Chinese and English. The
reducing inflammation and analgesia, promoting blood full search strategies for all databases are shown in Addi-
circulation, improving microcirculation, so as to delay tional file 2.
the progression of the disease. The core of exercise ther-
apy is the active participation of patients. Proper exercise Inclusion criteria
can improve the function of knee joint, reduce pain and After our review of relevant studies, based on the PICOS
improve the quality of life of patients [10]. In addition, frameworks (population, intervention, comparison, out-
exercise therapy can also reduce the loss of bone den- come and study), the inclusion criteria for this review are
sity and prevent osteoporosis that may be secondary to as follows: (1) Population: Patients with knee osteoarthri-
KOA. Therefore, acupuncture and exercise therapy have tis, regardless of gender, age, race, nationality, duration
become important treatment methods for KOA. Studies of disease, excluding patients who had knee surgery. (2)
[11, 12] have reported that commonly used acupuncture Intervention: Treatment measures in the experimental
treatment methods mainly include traditional milliacu- group included only acupuncture + exercise therapy, or
puncture, electroacupuncture, floating acupuncture, etc. acupuncture + exercise therapy in addition to the con-
Exercise therapy includes knee joint activity and function trol group. Here, acupuncture refers to a separate stab-
exercises, and traditional Chinese sports such as “Yijin bing method, which does not include moxibustion. And
Jing” and “Baduan Jin.” Acupuncture and active exercise exercise therapy is active exercise training, not passive
training alone are effective in treating KOA, and there is activities such as massage. (3) Comparison: The control
relevant literature that has been published to confirm it group was treated with acupuncture or exercise therapy
[13–15], so it is necessary to improve the inclusion and or western medicine or exercise therapy combined with
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 3 of 21

western medicine. (4) Outcome: Outcomes must include mean differences (MD) and 95% confidence intervals
total efficiency rate and Visual Analogue Scale (VAS) and (CI) were used when outcomes were assessed by the
either the Western Ontario and Mcmaster Universities same scale. I2 statistical tests were adopted to assess the
Osteoarthritis Index (WOMAC) or Lysholm Knee Scale heterogeneity among studies. A fixed-effects model was
(LKS). Range of motion (ROM) can also be included. (5) applied to combine the data if the I2 < 50% and p > 0.05.
Study: High-quality (Jadad ≥ 4) RCTs, published in Eng- If I2 > 50% and p < 0.05 implies high heterogeneity, a
lish or Chinese. random-effects model was used for meta-analysis and
subgroup analysis or sensitivity analysis was considered
Exclusion criteria to determine the source of heterogeneity. The total effi-
The exclusion criteria for this review are as follows: (1) ciency rate is dichotomous data and categorized into
the experimental group that received treatments other two levels ((1) effective and (2) inefficacious). The total
than acupuncture and exercise therapy, such as moxibus- efficiency rate means the percentage of the total num-
tion and Tuina massage; (2) non-RCTs; (3) low-quality ber of participants categorized in the first two levels.
article (Jadad < 4); and (4) unable to get full text or incom- In addition, we used funnel plot to explore publication
plete article data. bias, and then, Stata/MP 14.0 was used to perform Egg-
er’s test on the funnel plot to verify whether publication
Data extraction bias existed.
Two reviewers (J.Ch. and Y.S.W.) screened the stud-
ies and collected the data independently according to
the inclusion and exclusion criteria. The information of Trial sequential analysis
author, publication year, demographics of participants, Meta-analysis usually requires multiple tests, and ran-
intervention, treatment frequency and times, duration, dom errors that may sometimes lead to false significant
outcomes and Jadad score were recorded. All studies results when data are accumulated, and the increased
were managed with Endnote X9. Disagreements were frequency of statistical tests in a meta-analysis
resolved by discussion or umpired with a third reviewer increases the possibility of reporting such results [16].
(Z.X.L.). However, trial sequential analysis (TSA) overcomes the
shortcomings of classical meta-analysis and corrects
Quality and risk‑of‑bias assessment for the chances of type I error [17].
We assessed the quality of the studies using an improved TSA.0.9.5.10 beta was used for sequential analyses. If
Jadad scale (0–3: low quality, 4–7: high quality), and only the Z-curve exceeds the traditional boundary but does
studies with high quality (Jadad ≥ 4) were included. The not cross the TSA boundary, it suggests that a false
scores were given independently by two reviewers (J.C. positive error may be made. If it intersects the TSA
and Y.S.W.). If the results were inconsistent, they were boundary, it suggests that the meta-analysis results are
discussed with a third reviewer (Z.X.L.). robust, even if the RIS is not reached. The Z-curve did
Two reviewers (J.C. and Y.S.W.) also separately evalu- not intersect with the traditional cut-off value and the
ated the risk of bias. The evaluation was based on the TSA cut-off value, and the positive or negative conclu-
Cochrane Handbook for Systematic Review of Interven- sion could not be drawn. The Z-curve intersects the
tions, edition 5.3. Items include: (1) random sequence null line, indicating no significance [18]. We set a two-
generation (selection bias); (2) allocation concealment sided 5% type I error risk (α) and 20% type II error risk
(selection bias); (3) blinding of participants and person- (β) to calculate the amount of information needed, with
nel (performance bias); (4) blinding of outcome assess- a 20% relative risk (RRR) reduction and a control event
ment (detection bias); (5) incomplete outcome data rate derived from data from the meta-analysis.
(attrition bias); (6) selective reporting (reporting bias);
and (7) other bias. The quality of the included studies was
rated as low/unclear/high risk of bias (low risk of bias as Certainty of the evidence
“yes,” high risk of bias as “no,” otherwise was “unclear”). The Grading of Recommendations Assessment, Devel-
In the case of disagreements, a third reviewer (Z.X.L.) opment and Evaluation (GRADE) system was used to
was involved. assess the certainty of the evidence of each outcome.
Each outcome was evaluated from the following five
Statistical analysis aspects: limitations, inconsistency, indirectness, impre-
We used Review Manager 5.3 software provided by cision and publication bias. The certainty of the evi-
the Cochrane Collaboration for data analyses and pre- dence was categorized as “high,” “moderate,” “low,” or
sented the final result. For the continuous data, the “very low.”
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 4 of 21

Result retrieved, and 198 studies were excluded with reasons

Selection and inclusion of studies listed as the following: not RCT (n = 22), unavailable
A total of 1,124 studies were initially screened (Pub- data(n = 13), incorrect outcome measures (n = 73), low
Med = 171, EMBASE = 92, The Cochrane Library = 155, quality (n = 28) and others (n = 62). In the end, 11 RCTs
Web of Science = 116, CNKI = 154, Wan Fang Data = 179, were included, and 9 were written by Chinese in Chinese
Vip = 69, CBM = 182, other = 6). After primary searches [9, 19–26], 2 of which were written by Chinese in English
from the databases, 1124 studies were screened. After [27, 28]. The detailed screening process is shown in Fig. 1.
duplicates removed, reading the titles and abstracts, And the list of excluded records with reasons is provided
915 studies were excluded. Full texts of 209 studies were in Additional file 3.

Fig. 1 Flowchart of the selection process

Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 5 of 21

Characteristics of included studies publication bias. The Egger’s test of VAS score obtained
A total of 11 RCTs (one three-arm trial) involving 12 p = 0.838 > 0.05, indicating no publication bias.
datasets with 774 KOA individuals were included. All
of the studies were published between 2011 and 2022 Trial sequential analysis
in English or Chinese. The sample size ranged from 56 Twelve RCTs reported the total efficiency rate, which
to 77. All experimental groups received acupuncture were analyzed sequentially, with a type I error of 5% and
combined with active exercise training. Among them, a statistical power of 80%. The information axis was set
acupuncture included traditional milliacupuncture, as the cumulative sample size, and the sample size was
electroacupuncture and floating acupuncture, while used as the expected information value (RIS). Figure 4
active exercise training included Yijin Jing, Baduan Jin, [9, 19, 21, 23, 25–27] shows that the Z-curve crossed
walking, functional training around the knee joint. The the conventional boundary value and the TSA boundary
control groups underwent acupuncture, active exercise value, indicating that the results obtained from this meta-
training, oral western medicine or exercise combined analysis were robust and the efficacy of acupuncture
with western medicine. Characteristics of these studies combined with active exercise training in the treatment
are shown in Tables 1 and 2. of KOA was positive. Meantime, the penalty curve also
exceeded the traditional boundary value and reached the
RIS value, which made the meta-analysis result more sta-
Methodological quality of included studies ble. In Fig. 5 [19, 20, 22, 24, 28], the Z-curve also crossed
The methodological quality of most included RCTs was the conventional boundary value and the TSA boundary
generally “high” (Jadad ≥ 4), according to the quality value, indicating that the results obtained from this meta-
assessment criteria with improved Jadad scale (Table 1). analysis were robust. The penalty curve exceeded the tra-
All the trials mentioned the randomized allocation of ditional boundary value but did not reach the RIS value.
participants. Selective reporting was generally uncer- So it needs further research in future.
tain in the trials due to the inaccessibility of the trial
protocol.
Meta‑analysis results
Based on various outcome measures (the total efficiency
Risk of bias in studies rate, VAS, WOMAC, LKS, ROM), different pooled data
The plot of the risk of bias for each included study is from 12 trials were used. The data were divided into
shown in Fig. 2. The 12 trials (one three-arm trial) were stratified analyses according to different interventions of
at low risk. All of 11 studies reported random sequence control groups.
generation and were assessed as low risk. Ten studies [9,
19, 20, 22, 24–28] were assessed as unclear risk, and two Combination group versus acupuncture group
[21, 23] were assessed as low risk in the aspect of allo- Result of the total efficiency rate
cation concealment. In blinding of participants and per- A total of seven studies [9, 19, 21, 23, 25–27] involving
sonnel, two studies [19, 23] were assessed as unclear risk, 441 KOA individuals compared the total efficiency rate
one study [21] was assessed as low risk, and eight studies of acupuncture combined with active exercise training
[9, 20, 22, 24–28] were assessed as high risk. Also, seven and acupuncture for KOA. The results demonstrated
studies [9, 20, 22, 24–27] were assessed as unclear risk that combined treatment was superior to acupuncture
and four studies [19, 21, 23, 28] were assessed as low risk in the total efficiency rate [RR = 1.13, 95%CI (1.05, 1.22),
in the blinding of the outcome assessment. Of all these 11 I2 = 0%, P = 0.70] (Fig. 6).
studies were judged to be low risk in incomplete outcome
data and selective reporting. Finally, 11 studies were Result of the VAS
assessed as unclear risk in other bias. A total of seven studies [9, 19, 21, 23, 25–27] reported
the VAS score in 441 KOA individuals. The results
showed that the combined group was better at reducing
Publication bias pain than the acupuncture group [MD =  − 0.74, 95%CI
We first made funnel plots of total efficiency rate and (− 1.04, − 0.43), I2 = 68%, P < 0.05] (Fig. 7A). By exploring
VAS score using Review Manager 5.3, but could not heterogeneity, we found the risk of bias in two trials [9,
determine whether the funnel plots were symmetrical 27] was high. After removing the two trials (the duration
(Fig. 3A, B). Therefore, we used Stata/MP 14.0 to ana- of treatment in these two trials was not 4 weeks, while the
lyze the publication bias of total efficiency rate and VAS other trials were all 4 weeks), sensitivity analysis showed
score by Egger’s test. The results showed that the Egger’s that the overall effects did not change [MD =  − 0.72,
test with total effective rate was p < 0.05, which may have 95%CI (− 0.88, − 0.56), I2 = 30%, P = 0.22] (Fig. 7B).
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 6 of 21

Table 1 Characteristics summary of included studies

References Age(E/C) Sample Intervention Frequency and times Duration Outcomes Jadad
size(E/C)
E C E C
abc
Ding [27] 51.7 ± 12.9/59.7 ± 10.4 26/30 Electroa- Electroacu- EA:2/w,10 EA:2/w,10 5 weeks 4
cupunc- puncture Exercise:3/w,15
ture + Yijinjing
abc
Jin [19] 59.77 ± 8.64/62.67 ± 8.24 30/30 Electroa- Electroacu- EA:3/w,12 Exercise: EA:3/w,12 4 weeks 6
cupunc- puncture 3/d,60
ture + Quadri-
ceps function
exercises
abc
Jin [19] 59.77 ± 8.64/60.40 ± 9.67 30/30 Electroa- Quadriceps EA:3/w,12 Exercise: Exercise: 4 weeks 6
cupunc- function 3/d,60 3/d,60
ture + Quadri- exercises
ceps function
exercises
abd
Li [28] 57.3 ± 11.6/56.2 ± 12.4 32/32 Acupunc- Isokinetic AT:5/w,20 Exercise: Exercise: 4 weeks 4
ture + Isoki- eccentric 1/d,28 1/d,28
netic eccentric exer-
exercise cise + West-
ern
medicine
abc
Lin [20] 49.63 ± 2.72/49.07 ± 3.06 30/30 Acupunc- Western AT:1/d,14 Exercise: 1/d,14 14 days 4
ture + Knee medicine 1/d,14
function
exercises
abc
Liu [21] 57.9 ± 8.1/56.0 ± 7.7 38/38 Acupunc- Acupunc- AT:1/d,20 Exercise: AT:1/d,20 4 weeks 7
ture + Isomet- ture 3/d,60
ric exercise
abc
Liu [22] 60.10 ± 6.77/61.15 ± 7.08 39/38 Floating Knee joint FA:1/2d,12 Exer- Exercise: 4 weeks 4
acupunc- strength cise: 1/2d,12 1/2d,12
ture + Knee train-
joint strength ing + West-
training ern
medicine
abce
Wang [23] 58.67 ± 5.72/57.17 ± 7.78 30/30 Acupunc- Acupunc- AT:1/d,20 AT:1/d,20 4 weeks 6
ture + Guided ture Exercise:2/d,40
training
abc
Wang [24] 56.80 ± 6.45/59.53 ± 7.11 30/30 Acupunc- Western AT:1/d,20 Exercise: 2/d,40 20 days 4
ture + Knee medicine 1/d,20
flexion
and extension
exercises
abcd
Wang [9] 57.77 ± 8.32/57.54 ± 8.20 35/35 Acupunc- Acupunc- AT:1/d,15 Exercise: AT:1/d,15 3 weeks 4
ture + Walking ture 1/d,15
and squatting
abc
Wu [25] 53.79 ± 7.13/53.81 ± 6.15 36/36 Acupunc- Electroacu- AT EA: 3/w,12 4 weeks 4
ture + Squat- puncture and Exercise:1/w,4
ting
abce
Zheng [26] 57.01 ± 5.59/58.63 ± 5.07 29/30 Acupunc- Acupunc- AT:5/w,20 Exercise: AT:5/w,20 4 weeks 4
ture + Badu- ture 5/w,20
anjin
a
Total efficiency rate; bVAS: Visual analogue scale; cWOMAC: The Western Ontario and Mcmaster Universities Osteoarthritis Index; dLKS: Lysholm Knee Scale; eROM:
Range of motion; E/C: Experimental group/control group; EA: Electroacupuncture; AT: Acupuncture treatment; FA: Floating acupuncture; d: day; w: week;

Because of the heterogeneity of the VAS score, a P = 0.08], [MD =  − 1.15, 95%CI (− 1.46, − 0.83), I2 = 0%,
subgroup analysis of active exercise training after P = 0.33] (Fig. 7C). The results of the subgroup analysis
acupuncture and active exercise training with nee- also suggested that exercise during acupuncture might
dles showed that heterogeneity was reduced in both be more effective than exercise after acupuncture in
groups [MD =  − 0.55, 95%CI (− 0.84, − 0.25), I2 = 52%, reducing pain.
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 7 of 21

Table2 Acupuncture method, selected acupuncture points and exercise mode

References Acupuncture, acupoints and exercise

Ding [27] Electroacupuncture, 5 main points,Yanglingquan(GB34),Liangqiu(ST34),

Zusanli(ST36), Neixiyan(EX-LE4) and Dubi(ST35) + Yijinjing
Jin [19] Electroacupuncture, 7 main points, Dubi(ST35), Neixiyan(EX-LE4),Xuehai(SP10), Liangqiu(ST34), Yanglingquan(GB34), Zusanli(ST36)
and Yinlingquan(SP9) +
Quadriceps function exercises
Li [28] Acupuncture, 5 points, Heding (EX-LE2), Dubi (ST35), Neixiyan (EX-LE4), Yinlingquan (SP9) and Yanglingquan (GB34) + Isokinetic eccentric
exercise
Lin [20] Acupuncture, 1 point, Chize(LU5) + Knee function exercises
Liu [21] Acupuncture, 2 points, Neixiyan(EX-LE4) and Waixiyan(ST35) + Isometric exercise
Liu [22] Floating acupuncture, Ashi points, + Knee joint strength training
Wang [23] Acupuncture, 12 points, bilateral Pishu(BL20), bilateral Shenshu(BL23),
Guanyuan(RN4), Zusanli(ST36), Neixiyan(EX-LE4), Dubi(ST35), Xuehai(SP10), Liangqiu(ST34), Yanglingquan(GB34)
and Yinlingquan(SP9) + Guided training
Wang [24] Acupuncture, 9 points, Neixiyan(EX-LE4), Waixiyan(ST35),Heding(EX-LE2), Liangqiu(ST34), Xuehai(SP10), Yinlingquan (SP9), Yanglingquan
(GB34), Zusanli(ST36) and Dazhu(BL11) + Knee flexion and extension exercises
Wang [9] Acupuncture, 20 points, Dubi (ST35), Neixiyan (EX-LE4),Xiyangguan(GB33),
Ququan(LR8),Liangqiu(ST34), Xuehai(SP10), Yinlingquan (SP9), Heding(EX-LE2),
Yanglingquan (GB34),Xiyan(EX-LE5) (All acupuncture points are bilateral) + Walking and squatting
Wu [25] Acupuncture, 4 points, Xuehai(SP10), Liangqiu(ST34), Yanglingquan(GB34) and Yinlingquan(SP9) + Squatting
Zheng [26] Acupuncture, 4 points, Xuehai(SP10), Liangqiu(ST34), Neixiyan(EX-LE4), Waixiyan(ST35), Yanglingquan (GB34) and Zusanli(ST36) + Badu-
anjin

Result of the WOMAC total score combined group could better improve the functional sta-
A total of seven studies [9, 19, 21, 23, 25–27] reported tus of KOA patients[MD =  − 7.69, 95%CI (− 18.34, 2.96),
the WOMAC total score in 441 KOA individuals. The I2 = 92%, P < 0.05] (Fig. 9A1).
results showed that the combined group was better at By analyzing the sources of WOMAC-dysfunction het-
relieving knee symptoms and improving knee func- erogeneity, we performed a sensitivity analysis. We found
tion than the acupuncture group [MD =  − 6.97, 95%CI that the heterogeneity decreased after excluding one trial
(− 10.74, − 3.19), I2 = 76%, P < 0.05] (Fig. 8A). By analyz- [27] with the duration of treatment for 5 weeks and fre-
ing the sources of WOMAC heterogeneity, we found that quency of treatment twice a week [MD =  − 1.66, 95%CI
after excluding one trial [22] (duration of treatment for (− 6.70, 3.38), I2 = 60%, P = 0.11] (Fig. 9A2).
5 weeks, frequency of treatment twice a week), heteroge- Result of the WOMAC-stiffness A total of three tri-
neity was reduced[MD =  − 5.21, 95%CI (− 7.91, − 2.52), als [9, 19, 27] reported WOMAC-stiffness in 186 KOA
I2 = 52%, P = 0.06] (Fig. 8B). individuals. The results showed that the combined
Due to the heterogeneity of the results, we also per- group was better at relieving knee stiffness than the
formed a subgroup analysis based on the time of acupuncture group[MD =  − 1.08, 95%CI (− 2.19, 0.02),
exercise intervention (active exercise training after acu- I2 = 87%, P < 0.05] (Fig. 9B1). By analyzing the sources of
puncture or active exercise training with needles), which WOMAC-stiffness heterogeneity, we found that hetero-
showed that knee function improved in both groups geneity was reduced after excluding a three-arm study
[MD =  − 7.09, 95%CI (− 12.16, − 2.01), I2 = 83%, P < 0.05], [19] [MD =  − 1.60, 95%CI (− 2.36, − 0.84), I2 = 60%,
[MD =  − 7.27, 95%CI (− 11.35, − 3.28), I2 = 0%, P = 0.7] P = 0.11] (Fig. 9B2).
(Fig. 8C). The results of the subgroup analysis also sug- Result of the WOMAC-pain A total of three trials [9, 19,
gested that exercise during acupuncture might be more 27] reported WOMAC-pain in 186 KOA individuals. The
effective in improving knee joint function than exercise results showed that the combined group was better at
after acupuncture. relieving pain than the acupuncture group[MD =  − 1.08,
Result of the WOMAC-dysfunction A total of three tri- 95%CI (− 2.57, 0.40), I2 = 58%, P = 0.09] (Fig. 9C1). By
als [9, 19, 27] reported WOMAC-dysfunction in 186 analyzing the sources of WOMAC-pain heterogene-
KOA individuals. The results showed that the dysfunc- ity, we found that heterogeneity was reduced after
tion score of the combined group was significantly lower excluding a three-arm study [19] [MD =  − 1.95, 95%CI
than that of the acupuncture group, indicating that the (− 3.39, − 0.51), I2 = 0%, P = 0.72] (Fig. 9C2).
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 8 of 21

Fig. 2 Risk of bias of included studies

Result of the ROM rate [RR = 1.31, 95% CI (1.18, 1.47), I2 = 48%, P = 0.10]
A total of two studies [23, 26] reported the ROM in 119 (Fig. 11).
KOA individuals. The results showed that the combined
group was better at improving joint range of motion than Result of the VAS
the acupuncture group [MD = 6.25, 95%CI (2.37, 10.04), A total of five studies [19, 20, 22, 24, 28] reported the
I2 = 0%, P = 0.71] (Fig. 10). VAS in 321 KOA individuals. The results showed that
the combined group was better at reducing pain than
the control group [MD = 1.42, 95% CI (− 1.85, − 1.00),
Combination group versus exercise or western medicine I2 = 65%, P = 0.02] (Fig. 12A). By exploring heterogeneity,
or exercise medicine group we found that the heterogeneity decreased after exclud-
Result of the total efficiency rate ing a three-arm trial [19] with only exercise and no other
A total of five studies [19, 20, 22, 24, 28] involving 321 treatment[MD =  − 1.24, 95%CI (− 1.57, − 0.91), I2 = 0%,
KOA individuals compared the total efficiency rate of P = 0.41] (Fig. 12B).
acupuncture combined with active exercise training with Due to the heterogeneity of the results, we further
exercise or western medicine or exercise medicine on performed a subgroup analysis of the duration of treat-
KOA. The results demonstrated that combination group ment. The results showed that heterogeneity was reduced
was superior to control group in the total efficiency in both groups [MD =  − 1.07, 95%CI (− 1.67, − 0.46),
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 9 of 21

Fig. 3 Publication bias of included studies. (A) total efficiency rate. (B) VAS
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 10 of 21

Fig. 4 TSA on comparison of combination group versus acupuncture in total efficiency rate. The straight black line represents the conventional
statistical boundary of P = 0.05. The blue line indicates the cumulative z-score of the meta-analysis. The red line indicates the TSA boundary. The
green line represents the Z-curve after the penalty statistic. RIS represents the required size of information
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 11 of 21

Fig. 5 TSA on comparison of combination group versus exercise or western medicine or exercise medicine group in total efficiency rate. The
straight black line represents the conventional statistical boundary of P = 0.05. The blue line indicates the cumulative z-score of the meta-analysis.
The red line indicates the TSA boundary. The green line represents the Z-curve after the penalty statistic. RIS represents the required size
of information
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 12 of 21

Fig. 6 Forest plot of total efficiency rate in comparison with combination group versus acupuncture group

Fig. 7 Forest plot of VAS in comparison with combination group versus acupuncture group. (A) All studies. (B) After sensitivity analysis. (C) After
subgroup analysis
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 13 of 21

Fig. 8 Forest plot of WOMAC total score in comparison with combination group versus acupuncture group. (A) All studies. (B) After sensitivity
analysis. (C) After subgroup analysis

I2 = 46%, P = 0.17], [MD =  − 1.75, 95%CI (− 2.03, − 1.48), results showed that the combined group was better at
I2 = 10%, P = 0.33] (Fig. 12C). The results of the subgroup relieving knee symptoms and improving knee func-
analysis also indicated that the longer the treatment tion than the control group [MD =  − 7.05, 95%CI
period, the more pain reduction in KOA individuals. (− 11.43, − 2.66), I2 = 86%, P < 0.05] (Fig. 13A). By ana-
lyzing the sources of WOMAC heterogeneity, we found
that after excluding one trial [24] with exercise dur-
Result of the WOMAC total score ing acupuncture and treatment duration of 20 days,
A total of four studies [19, 20, 22, 24] reported the heterogeneity was reduced [MD =  − 5.36, 95%CI
WOMAC total score in 257 KOA individuals. The (− 9.26, − 1.46), I2 = 62%, P = 0.07] (Fig. 13B).
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 14 of 21

Fig. 9 Forest plot of WOMAC-dysfunction (A), WOMAC-stiffness (B), WOMAC-pain (C) in comparison with combination group versus acupuncture
group. (1) All studies. (2) After sensitivity analysis
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 15 of 21

Fig. 10 Forest plot of ROM in comparison with combination group versus acupuncture group

Fig. 11 Forest plot of total efficiency rate in comparison with combination group versus exercise or western medicine or exercise medicine group

Due to the heterogeneity of the results, we also per- mainly attributed to the risk of bias of included studies
formed a subgroup analysis based on the type of exercise and imprecision and publication bias generated by small
(isometric strength training + isotonic strength train- sample sizes.
ing or not), which showed that knee function improved
in both groups [MD =  − 3.41, 95%CI (− 6.49, − 0.32), Discussion
I2 = 0%, P = 0.32], [MD =  − 10.44, 95%CI (− 12.81, − 8.07), This systematic review and meta-analysis of 11 studies
I2 = 40%, P = 0.20] (Fig. 13C). involving 774 KOA individuals aimed at assessing the
Result of the WOMAC-dysfunction A total of two tri- effectiveness of acupuncture combined with active exer-
als [19, 22] reported WOMAC-dysfunction in 137 KOA cise training on KOA and improvement in knee pain and
individuals. The results showed that the dysfunction function. Ultimately, the results of our study indicated
score of the combined group was significantly lower that acupuncture combined with active exercise training
than that of the control group, indicating that the com- might be an effective treatment for KOA individuals.
bined group could better improve the functional status The results of the meta-analysis were generally stable,
of KOA individuals [MD =  − 5.34, 95%CI (− 7.81, − 2.87), but the analysis of the WOMAC score required more dis-
I2 = 20%, P = 0.26] (Fig. 14A). cussion. The WOMAC was mainly composed of dysfunc-
Result of the WOMAC-stiffness A total of two trials tion, stiffness and pain. In addition to statistical analysis
[19, 22] reported WOMAC-stiffness in 137 KOA indi- of the WOMAC total score, we also combined the effect
viduals. The results showed that the combined group was size of dysfunction, stiffness and pain, respectively. How-
better at relieving knee stiffness than the control group ever, when comparing the combined group with the
[MD =  − 0.39, 95%CI (− 0.73, − 0.06), I2 = 0%, P = 0.47] acupuncture group, we found statistical heterogeneity
(Fig. 14B). in WOMAC-dysfunction (I2 = 92%, P < 0.05), WOMAC-
Result of the WOMAC-pain A total of two trials [19, stiffness (I2 = 87%, P < 0.05) and WOMAC-pain (I2 = 58%,
22] reported WOMAC-pain in 137 KOA individuals. P = 0.09) after combined effect size, respectively. There-
The results showed that the combined group was better fore, we conducted sensitivity analysis to find the source
at relieving pain than the control group [MD =  − 1.43, of heterogeneity, and only the heterogeneity of pain indi-
95%CI (− 2.13, 0.73), I2 = 0%, P = 0.50] (Fig. 14C). cators was significantly reduced (I2 = 0%, P = 0.72), while
the heterogeneity of dysfunction ­(I2 = 60%, P = 0.11) and
Certainty of the evidence stiffness (I2 = 60%, P = 0.11) decreased after sensitivity
The results of the GRADE are shown in Additional file 4. analysis, but it was still more than 50%, which was not
The certainty of the evidence of total efficiency rate (com- suitable for subgroup analysis and other analyses due to
bination group versus acupuncture group) was graded as the limitation of the number of included studies. When
“moderate,” and the rest outcomes were considered as the combined group was compared with the non-acu-
“low” or “very low.” The reasons for downgrading were puncture group, there was no statistical heterogeneity
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 16 of 21

Fig. 12 Forest plot of VAS in comparison with combination group versus exercise or western medicine or exercise medicine group. (A) All studies.
(B) After sensitivity analysis. (C) After subgroup analysis

in dysfunction (I2 = 20%, P = 0.26), stiffness (I2 = 0%, exercise therapy and other conservative treatment and
P = 0.47) and pain (I2 = 0%, P = 0.50), and the results were surgical treatment [35]. In recent years, complemen-
stable. Anyhow, almost all results showed that the com- tary and alternative medicine (CAM) has been widely
bination therapy significantly improved functional activ- accepted and applied in clinical practice. As comple-
ity, alleviated joint stiffness and reduced pain in KOA mentary alternative therapies, acupuncture and exer-
individuals. cise therapy have obvious clinical effects on KOA,
At present, the etiology and pathophysiological and there are no obvious side effects compared with
mechanism of KOA are not clear. And some studies surgical and western drugs, and patients have a high
[29–34] believed that the factors leading to the occur- degree of acceptance. According to Chinese medicine,
rence of KOA included age, obesity, environmental KOA belongs to the category of “paralysis” and “bone
and genetic factors, malnutrition, joint ligament injury, paralysis,” which are generally caused by insufficient
meniscal injury, knee fracture and knee instability. Cur- qi and blood, liver and kidney deficiency and external
rently, the main clinical measures for the treatment of evil invasion and damage to the knee joint [36]. Com-
KOA include NSAIDs, intra-articular injection, physi- monly used acupuncture tools for clinical knee joint
cal therapy, traditional Chinese medicine treatment, treatment include millineedle, electroacupuncture,
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 17 of 21

Fig. 13 Forest plot of WOMAC total score in comparison with combination group versus exercise or western medicine or exercise medicine group.
(A) All studies. (B) After sensitivity analysis. (C) After subgroup analysis

floating needle, etc. [37]. Relevant studies have shown muscle function and acupuncture can improve early
that acupuncture can significantly reduce pain, improve KOA muscle atrophy, significantly increase the expres-
dysfunction and improve the quality of life of KOA indi- sion of Pax7, MyoD, MyoG, MyHC1 and other mus-
viduals [15, 38]. The mechanism of action of acupunc- cle-generating molecular markers and Wnt/β-catenin
ture in the treatment of KOA includes: (1) Acupuncture pathway-related gene proteins, promote the prolifera-
can scavenge free radicals [39], inhibit the expression tion and differentiation of skeletal muscle stem cells to
of osteopontin (OPN), matrix metalloproteinase-3 achieve the regeneration and repair of damaged skeletal
(MMP-3), transforming growth factor-β1 (TGF-β1) muscle and have a protective effect on early KOA joint
and insulin-like growth factor I (IGF-I) and serum chondrocytes and type II collagen metabolism [43, 44].
nitric oxidein peripheral blood and synovial fluid of (3) One study [1] has shown that compared with other
joints, promote the repair of joint cartilage, relieve and acupuncture, electroacupuncture has a better analgesic
improve local inflammatory symptoms of knee joint and anti-inflammatory mechanism for KOA [45, 46],
and play a role in the treatment of KOA [40–42]. (2) and electroacupuncture on local acupuncture points
KOA individuals are often accompanied by abnormal of the knee joint can not only repair knee cartilage, but
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 18 of 21

Fig. 14 Forest plot of WOMAC-dysfunction (A), WOMAC-stiffness (B), WOMAC-pain (C) in comparison with combination group versus exercise
or western medicine or exercise medicine group

also regulate knee microcirculation, increase endog- joint during active exercise can regulate the expression of
enous opioid levels and significantly reduce plasma cor- TNF-α, MMP-13 and integrin-α1β1, inhibit the apoptosis
tisol levels [47–49]. of chondrocytes and then delay the degeneration of joint
At the same time, many clinical guidelines [50–53] rec- cartilage [61, 63].
ommend exercise therapy as the main measure to prevent Both acupuncture and active exercise therapy have
and treat KOA. Exercise therapy can not only delay the good effects on KOA, and relevant studies [64–66] have
degeneration of cartilage tissue, improve muscle strength shown that combining the two treatment modalities
and restore the normal function of musculoskeletal, but shows more excellent results than acupuncture alone or
also relieve pain, improve joint mobility, protect soft tis- active exercise training alone or only oral western medi-
sues, promote blood circulation, improve their quality of cine or exercise combined with western medicine.
life and achieve the purpose of improving comprehen- Our review was conducted by developing strict inclu-
sive curative effect [54–58]. The mechanism of exercise sion/exclusion criteria and controlling for methodologi-
therapy in the treatment of KOA can be summarized as cal quality. This meta-analysis searched eight electronic
follows: (1) Inhibit the expression of inflammatory fac- databases to provide a comprehensive study. Moreover,
tors such as IL-1β, IL-6, IL-8 and TNF-α, thereby reduc- all the included studies were of high quality (Jadad ≥ 4),
ing the inflammatory response of patients, improving the and the conclusions were relatively reliable. In addition,
immune related indexes such as Tim-3 and PD-1 in KOA we conducted a group comparison (combined treatment
individuals and inhibiting their autoimmune response versus acupuncture alone, combined treatment versus
[59]. (2) KOA individuals often have knee stress imbal- non-acupuncture) to more fully illustrate the effective-
ance and lower extremity mechanical axis abnormalities ness of acupuncture combined active exercise training
[60]. Exercise therapy can correct the stress imbalance of for pain and dysfunction in KOA individuals. However,
the lower limb joints of KOA individuals, adjust the state there are several potential limitations in our study. Firstly,
of soft tissue dysfunction around the joints of the lower some of the studies included in our review had methodo-
limbs, reduce the angle of the joint space and improve logical flaws. The most common methodological deficit
the biomechanical indexes [61, 62]. (3) The mechani- was lack of blinding of participants, therapists and asses-
cal signals generated by the squeezing effect on the knee sors. Secondly, most of the included studies had small
Chen et al. Journal of Orthopaedic Surgery and Research (2023) 18:921 Page 19 of 21

sample sizes (n < 50). And larger, high-quality studies are responsible for extracting data and quality assessment. All authors made
substantial contributions to conception and design and interpretation of the
needed for further analysis in future. Thirdly, the types data, drafted the manuscript and gave final approval of the final version. SJ
of acupuncture in the included studies had different acu- is responsible for the overall content. All authors read and approved the final
puncture points and the number of acupuncture points manuscript.
selected during treatment, as well as certain differences Funding
in the mode and intensity of exercise, which might be The author(s) disclosed receipt of the following financial support for the
the reason for the large heterogeneity. Therefore, a more research, authorship and/or publication of this article: This review was sup-
ported by Sichuan Administration of Traditional Chinese Medicine (Project No.
detailed meta-analysis is needed as a next step. Finally, 2020lc0080).
there were differences in follow-up time for the studies
included in this review. Most outcomes were measured Availability of data and materials
The original contributions presented in the study are included in the article/
after treatment, and only six studies reported follow-up Supplementary material. Further inquiries can be directed to the correspond-
outcomes. The effect of follow-up time on the effect of ing authors.
acupuncture combined with active exercise training on
KOA needs to be further explored. Declarations
Ethics approval and consent to participate
Conclusion Not applicable.
Meta-analysis showed that acupuncture combined with
active exercise training had significant efficacy and few Consent for publication
Not applicable.
side effects in reducing pain, improving knee function,
increasing joint range of motion and overall effective rate Competing interests
in KOA individuals, and deserved further promotion. The authors declare that they have no competing interests.

However, due to some shortcomings in this meta-analy- Author details

sis, further trials and analyses are needed to confirm this. 1
School of Health Preservation and Rehabilitation, Chengdu University of Tra-
ditional Chinese Medicine, Chengdu, Sichuan, China. 2 Rehabilitation Depart-
ment, Hospital of Chengdu University of Traditional Chinese Medicine, No.39,
Abbreviations 12 Bridge Road, Jinniu District, Chengdu 610000, Sichuan, China. 3 School
KOA Knee osteoarthritis of Medical and Life Sciences, Chengdu University of Traditional Chinese Medi-
RCTs Randomized controlled trials cine, Chengdu, Sichuan, China.
VAS Visual analogue scale
WOMAC Western Ontario and Mcmaster Universities Osteoarthritis Index Received: 6 August 2023 Accepted: 22 November 2023
LKS Lysholm Knee Scale
ROM Range of motion
MD Mean difference
SD Standard deviation
CI Confidence interval References
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