Acupuncture of different treatment frequencies in knee osteoarthritis a pilot randomised controlled Trial

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Research Paper
Acupuncture of different treatment frequencies in
knee osteoarthritis: a pilot randomised
controlled trial
Lu-Lu Lina, Jian-Feng Tub, Li-Qiong Wanga, Jing-Wen Yanga, Guang-Xia Shia, Jin-Ling Lia, Na Zhanga,
Jia-Kai Shaob, Xuan Zoua, Cun-Zhi Liua,*
Abstract
This 16-week randomised controlled trial (8-week treatment followed by 8-week follow-up) evaluated the symptomatic improvement
in patients with knee osteoarthritis on 3 sessions per week of acupuncture (TSWA) compared to 1 session per week of acupuncture
(OSWA). Sixty participants were randomised to either the TSWA or the OSWA group in a 1:1 ratio. The primary outcome was
response rate, defined as the percentage of participants achieving$2 points decrease on the numerical rating scale (NRS) and$6
points decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared
with baseline. Additional outcomes included response rates at weeks 4 and 16, NRS,WOMAC, Patient Global Assessment, 12-item
Short Form Health Survey (SF-12), and treatment credibility and expectancy. No significant difference was seen in response rate
between TSWA and OSWA groups at week 8 (64.7% vs 50.0%; difference, 14.7 percentage points [95% CI, 210.1 to 39.4
percentage points], P 5 0.435). At weeks 4 and 16, the TSWA group had higher response rates than the OSWA group (week-4:
difference, 44.7 percentage points [95%CI, 23.2-66.1 percentage points], P5 0.001; week-16: difference, 46.0 percentage points
[95%CI, 24.4-67.6 percentage points], P, 0.001). Participants in the TSWA group experienced significantly greater improvements
in NRS,WOMAC function, and Patient Global Assessment than those in theOSWAgroup. There were no significant between-group
differences in WOMAC stiffness and SF-12. In summary, TSWA immediately improved knee pain and dysfunction compared with
OSWA. In addition, the benefit of TSWA persists throughout follow-up.
Keywords: Knee osteoarthritis, Acupuncture, Treatment frequency, Clinical trial
1. Introduction
Osteoarthritis is a common musculoskeletal disorder and has
affected 250million people worldwide. Knee osteoarthritis (KOA) is
the most prevalent osteoarthritis and accounts for approximately
85% of the osteoarthritis burden.11 More than 8% of Chinese
adults aged 45 years or older suffer from symptomatic KOA.24 The
costs of KOA greatly surpass the direct healthcare costs, making it
a substantial public health problem.14 In the published osteoar-
thritis guidelines, nonpharmacological therapies are widely recom-
mended.10,17 Recommendations for managing KOA focus on
improving symptoms as important goals. Acupuncture is one of the
most common nonpharmacological therapies for symptoms
associated with musculoskeletal conditions. Studies have shown
that acupuncture is superior to sham as well as no acupuncture in
relieving knee pain and dysfunction23,25; however, others have
reported no differences.8,12,22,30 The inconsistency of these
studies may result from variations in the design characteristics
(eg, frequency of acupuncture treatment, interventions and
cointerventions used).
Doses, such as the frequency of treatment, elicitation of De-Qi (a
sensation including soreness, numbness and heaviness), and the
number of points stimulated, are important for the effect of
acupuncture. Among them, the frequency of acupuncture plays an
important role and is relevant to cumulative effects.5,7,23 We found
that the frequency of acupuncture in trials that showed negative
results8,12 is significantly less than that in other trials that showed
positive results.2,31 In most previous trials, participants with chronic
pain received acupuncture 1 to 2 sessions/week.21 However,
patients with chronic diseases usually receive acupuncture 3 to 5
sessions/week in China.6,20 As we know, effects of different
frequencies of acupuncture for KOA have not been explored in
randomisedcontrolled trials (RCTs). Therefore,weconductedastudy
ofKOA tocompare theeffects of 3 sessionsperweekof acupuncture
(TSWA) with 1 session per week of acupuncture (OSWA).
2. Methods
2.1. Design
This is an exploratory 2-armed RCT. The study duration was 16
weeks: 8-week treatment and 8-week follow-up. This study was
Sponsorships or competing interests that may be relevant to content are disclosed
at the end of this article.
a Acupuncture Research Center, School of Acupuncture-Moxibustion and Tuina,
Beijing University of Chinese Medicine, Beijing, China, b Department of Acupunc-
ture andMoxibustion, BeijingHospital of Traditional ChineseMedicine, affiliated with
Capital Medical University, Beijing, China
*Corresponding author. Address: Acupuncture Research Center, School of
Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No.
11, Bei San Huan Dong Lu, Chaoyang District, Beijing 100029, China. Tel.:186 10
53912201. E-mail address: lcz623780@126.com (C.-Z. Liu).
Supplemental digital content is available for this article. Direct URL citations appear
in the printed text and are provided in the HTML and PDF versions of this article on
the journal’s Web site (www.painjournalonline.com).
PAIN 161 (2020) 2532–2538
© 2020 International Association for the Study of Pain
http://dx.doi.org/10.1097/j.pain.0000000000001940
2532 L.-L. Lin et al.·161 (2020) 2532–2538 PAIN®
Copyright © 2020 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
mailto:lcz623780@126.com
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http://dx.doi.org/10.1097/j.pain.0000000000001940
conducted in accordance with the Declaration of Helsinki and
was approved by the medical ethical review committee of Beijing
Hospital of Traditional Chinese Medicine, affiliated with Capital
Medical University (No 2017BL-076-01). The protocol was
registered (clinicaltrials.gov NCT03359603) and published.18
2.2. Participants
Participants were recruited from Beijing Hospital of Traditional
Chinese Medicine between December 2017 and January 2019
through WeChat (a social networking site), print advertisements,
and signs posted at outpatient units.
Eligible participantsweremenorwomenbetween the ages of 45
and 75 years; met the diagnosis of KOA13; had symptoms related
to KOA for $6 months; met the radiologic confirmation of KOA
(Kellgren–Lawrence grade16 Ⅱ-Ⅲ); had average knee pain $4 on
an 11-point numerical rating scale (NRS)15 in the past week; and
agreed to refrain from the routine use of analgesics. If participants
need rescue medication, they were provided with Tylenol
(Shanghai Johnson Pharmaceutical Co, Ltd, Shanghai, China;
0.65 g/8 hour), except during the 48 hours before evaluation.
The exclusion criteria were: history of knee surgery or waiting for
surgery; knee pain caused by other diseases (eg, joint loose
bodies, severe effusion of the joint cavity, malignant tumors, and
autoimmune diseases); history of arthroscopy in the past year or
intra-articular injection in the past 4 months; acupuncture
treatment in the past 3months; severe organic ormental diseases;
pregnant or lactating women; coagulation disorders; needle
phobia; and involvement in other clinical trials in the past 3months.
2.3. Randomization and blinding
Participants were randomly allocated in a 1:1 ratio to 1 of the 2
groups through a central randomization system using block of 6.
The randomization sequence was generated by an independent
researcher using SAS 9.3 software and was embedded into
Guideline Medicine (Beijing Guide Technology Co, Ltd, Beijing,
China, Website: http://zhinanmed.com/). Allocation was per-
formed by clinical research coordinator (CRC) who was not
involved in treatment or assessment. The CRC inputted each
participant’s name into thewebsiteand then randomnumber and
group assignment were sent to the CRC immediately through
short message. The outcome assessor and statistician were
blinded to group allocation. The acupuncturist and participants
were not blinded because of the nature of intervention.
2.4. Interventions
The acupuncture strategies were developed by a consensus of
acupuncture and orthopedics experts based on the distinguished
Chinese textbook,9 as well as traditional Chinese medicine
meridian theory to treat knee pain, known as the Bi syndrome.
Two (1 female and 1 male) licensed acupuncturists delivered
treatments. They both had $10 years of clinical experience and
attended a 2-hour centralised training before recruitment. Hwato
disposable acupuncture needles (Suzhou, China; 0.30 3 25 or
0.30 3 40 mm) were used.
All participants received acupuncture at 5 obligatory acupoints
(ST 35, EX-LE5, LR 8, GB 33, and an Ahshi point) and 3 adjunct
acupoints. Three adjunct acupoints were chosen from 22
acupoints by the acupuncturists according to meridian theory
(Table 1). Both knees were needled if affected.
Needles were inserted at an angle of 30-45 or 90˚ and a depth
of 10 to 30 mm. The needles were stimulated manually for $10
seconds to achieve De-Qi and then paired electrodes from
HANS-200A acupoint nerve stimulator (Nanjing Jisheng Medical
Co, Ltd, Nanjing, China) were used at LR8-GB33 and 2 adjunct
acupoints by the acupuncturists. The electroacupuncture lasted
for 30 minutes with a dilatational wave of 2/100 Hz and the
intensity of 0.1 to 1 mA depending on the participant’s comfort
level. To ensure the consistency of electrostimulation with the
unilateral KOA, participants with bilateral KOA only received
electrostimulation on 1 knee (the most symptomatic knee at
baseline). The use of other treatments, such as injections of any
kind,moxibustion, ear acupuncture, or cupping, was not allowed.
All participants received 24 sessions (3 sessions/week) or 8
sessions (1 session/week) of electroacupuncture treatments over
8 weeks. Procedures and other treatment parameters were
identical in the 2 groups.
2.5. Outcomes
2.5.1. Primary outcomes
The primary outcome was response rate—the percentage of
participants achieving $2 points decrease on the NRS (0 “no
pain” to 10 “worst pain possible”) and $6 points decrease in
Western Ontario and McMaster Universities Osteoarthritis Index
(WOMAC)1 function (0 “no dysfunction” to 68 “maximum
dysfunction”) at week 8 compared with baseline.
2.5.2. Secondary outcomes
Secondary outcomes included response ratesmeasured at 4 and
16 weeks, NRS, 3 WOMAC subscales, Patient Global Assess-
ment (PGA) (0 “worst outcome” to 4 “best outcome”), and 12-
item Short Form Health Survey (SF-12)28 at 4, 8, and 16 weeks.
We assessed participants’ credibility and expectancy using the
Credibility of treatment scale26 after the first treatment. The
number of adverse events and the usage of Tylenol were
documented according to the reporting of participants and
acupuncturists from baseline to week 16. Feasibility outcomes
included recruitment rate, randomization rate, treatment compli-
ance, and participant retention rates. Compliance was calculated
as the proportion of acupuncture sessions received from the
expected sessions; this took into account participant adherence
to the treatment protocol.
2.6. Sample size
The pilot study aimed to explore symptomatic improvement in
patients with KOA on TSWA compared to OSWA. Based on
clinical experience, sample size was calculated to provide 80%
power if 70% of the TSWA group achieved response at 8 weeks,
compared with 30% of the OSWA group, at a two-tailed alpha
level of 0.05. This requires 60 participants, allowing for 20%
dropout.
2.7. Statistical analysis
The baseline characteristics and response rates described were
based on the modified intention-to-treat population, which
included participants who had $1 treatment. Missing data were
imputed using multiple imputations. Continuous variables are
presented as the mean (SD) or median (interquartile range).
Categorical variables are shown as the number and percent.
Response rates were evaluated with the x2 test. For secondary
outcomes with baseline data (3 WOMAC subscales, NRS, SF-
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12), a comparison between groups was assessed by a mixed-
effect model with repeated measurement analysis using corre-
sponding scale scores at all time-points as dependent variable,
treatment as the main factor, the baseline value as a covariate,
and a random intercept to model within-subject correlation. PGA
and the Credibility of treatment scale without baseline data were
compared between groups using Wilcoxon rank-sum test with
observed data. Mean changes from baseline for each outcome at
each time were compared within groups using paired t-tests.
Analyses were performed with SPSS (IBM SPSS Statistics,
New York), version 21.0 with 2-sided P , 0.05 considered
significant.
3. Results
Ninety-five participants were screened, and 60 were recruited
(recruitment rate of 63.2%) and randomly assigned (30 TSWA
group, 30 OSWA group) (randomization rate of 100%). A total of
50 (participant retention rate of 83.3%) participants completed
the follow-up assessment (Fig. 1). All 60 participants received$1
treatment sessions and were included in the intention-to-treat
analysis. Treatment groupswere similar at baseline (Table 2). The
mean number of sessions received was 22.1 (compliance was
92.1%) in the TSWA group and 7.2 (compliance was 90.0%) in
the OSWA group.
For the week-8 response rates, there was no between-group
difference (TSWA group 64.7% vs OSWA group 50.0%,
difference: 14.7 percentage points [95% CI, 210.1 to 39.4
percentage points], P 5 0.435). However, response rates were
significantly higher for the TSWA group than OSWA at weeks 4
and 16 (week-4: 58.0% vs 13.3%, difference: 44.7 percentage
points [95% CI, 23.2-66.1 percentage points], P5 0.001; week-
16: 60.7% vs 14.7%, difference: 46.0 percentage points [95%CI,
24.4-67.6 percentage points], P , 0.001) (Fig. 2 and Table 3;
Appendix Table 1, available as supplemental digital content at
http://links.lww.com/PAIN/B60).
Table 4 presents continuous outcomes over time. We found
no difference of Credibility of treatment scale between TSWA and
OSWA groups (19.0 (16.0, 23.5) vs 19.0 (17.8, 25.0), P5 0.716).
For NRS andWOMAC function, the TSWA group showed greater
improvement than the OSWA group (each P , 0.001) (Figs. 3
and 4). Although TSWA improvedmoreWOMAC pain and SF-12
Physical health scores compared with OSWA, these between-
group differences were not statistically significant (PWOMAC pain 5
0.061; PPhysical health 5 0.078) (Fig. 5). For WOMAC stiffness and
SF-12 Mental health scores, there were no between-group
differences (each P . 0.05). Although there was no significant
between-group difference in PGA at week 8 (P 5 0.801), there
were significant between-group differences at weeks 4 and 16
favouring the TSWA group (each P , 0.001). There were
significant within-group differences for change in all secondary
outcomes except for SF-12 at every time-point favouring TSWA
or OSWA group (Appendix Table 2, available as supplemental
digital content at http://links.lww.com/PAIN/B60). No participant
used the provided pain rescue medication (Tylenol).
In the TSWA group, 13.8% participants (4/29) reported
acupuncture-associated adverse events compared with 11.5%
participants (3/26) in the OSWA group. These adverse events
could remit within 2 weeks without treatment. The adverse effect
rates were higher than other studies that reported 0.13% to
0.14%.3,19,29 It may be that the definitions of adverse events in
those studies are more serious than our study. Furthermore, the
Table 1
Selection of 3 adjunct acupoints.
The locationof pain in the knee joint Affected meridian Alternative adjunct acupoints
Anterior Stomach meridian of foot-yangming ST32, ST34, ST36, ST40, EX-LE2
Posterior Bladder meridian of foot-taiyang BL39, BL40, BL57, BL60
Lateral Gallbladder meridian of foot-shaoyang GB31, GB34, GB36, GB39, GB41
Medial Foot three-yin meridian* SP4, SP6, SP9, SP10, KI3, KI10, LR3, LR7
* Foot 3 Yin Meridian consisted of Spleen Meridian of Foot-Taiyin, Kidney Meridian of Foot-Shaoyin, and Liver Meridian of Foot-Jueyin. If pain occurred in only one location of the affected knee joint, 3 adjunct acupoints were
chosen from those for the affected meridian. If more than 2 locations were affected, 3 adjunct acupoints were chosen from those for the relevant meridians.
Table 2
Participant demographic and baseline characteristics.
Variable TSWA group (n 5 30) OSWA group (n 5 30) P
Women, N (%) 25 (83.3) 20 (66.7) 0.136
Age, y, median (IQR) 61.5 (58.0, 67.0) 62.5 (55.7, 66.0) 0.347
Duration of disease, mo, median (IQR) 51.0 (36.0, 120.0) 30.0 (12.0, 102.0) 0.053
BMI, kg/m2, mean (SD) 25.4 (2.7) 25.8 (3.4) 0.600
NRS score (0-10), median (IQR) 7.0 (5.8, 7.0) 6.0 (5.0, 7.0) 0.131
WOMAC pain subscale (0-20), median (IQR) 7.5 (6.0, 10.0) 7.0 (6.0, 8.0) 0.161
WOMAC function subscale (0-68), mean (SD) 26.6 (6.6) 26.7 (5.7) 0.950
WOMAC stiffness subscale (0-8), median (IQR) 3.0 (2.0, 4.0) 3.0 (2.0, 4.0) 0.807
Physical health, SF-12* (0-100), median (IQR) 29.1 (23.2, 35.2) 30.6 (23.3, 33.8) 0.859
Mental health, SF-12* (0-100), median (IQR) 53.8 (38.5, 63.0) 56.3 (45.9, 58.9) 0.615
* Higher values indicate better status.
BMI, body mass index; IQR, interquartile range; NRS, numerical rating scale; OSWA, 1 session per week of acupuncture; SF-12, Medical Outcomes Study 12-item Short-Form Health Survey; TSWA, 3 sessions per week of
acupuncture; WOMAC, Western Ontario and McMasters Universities Osteoarthritis Index.
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2534 L.-L. Lin et al.·161 (2020) 2532–2538 PAIN®
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small sample size makes the adverse effect rate vulnerable by
chance and the site of needle stimulation maybe attributed to the
inconsistency. There were 2 serious adverse events not
associated with acupuncture (Appendix Table 3, available as
supplemental digital content at http://links.lww.com/PAIN/B60).
4. Discussion
We found that TSWA did not provide better responses at week-8
for people with KOA compared with OSWA. However, at 4 or 16
weeks, compared with the OSWA group, response rates in the
TSWA group were significantly higher. These results indicated
that TSWA acted quickly (,4 weeks) and its benefits persisted
$8 weeks after treatment. Interestingly, the effects of OSWA
seemed to be accumulative at week-8. Thus, TSWA might be
recommended for acute, short-term pain or dysfunction relief for
KOA. OSWA might be recommended for chronic, longer-term
treatment effect because it is associated with symptom
improvement beyond 8 weeks and is safe. For NRS, WOMAC
function and PGA, observed patterns were similar to those of
response rates, with better outcomes in the TSWA group.
WOMAC pain and Physical health scores were observed with
more favorable changes in the TSWA group but no significant
between-group differences (PWOMAC pain 5 0.061; PPhysical health
5 0.078). Overall, the therapeutic effects of TSWA occurred
earlier and lasted longer. The results corroborate those of Sun
et al.,23 who reported that the effect of acupuncturemay be dose-
dependent, with a higher dosage related to better outcomes.
To the best of our knowledge, no prior RCT has evaluated the
effect of different frequency acupuncture on KOA. Our results of
the TSWA group were congruent with the findings of our previous
trial27 that investigated the response rate of TSWA for KOA. Two
published trials have used response rates to assess the effect of
acupuncture on KOA.22,31 One study by Witt C et al.31 reported
that 52% of participants achieved $50% decrease in WOMAC
score after 8-week acupuncture (2 sessions per week for 4
weeks, weekly in the remaining 4 weeks). In our study, similar
result (46.7%, cutoff: 50%decrease inWOMAC score) was found
Figure 1. Trial flow chart (consolidated standards of reporting trials diagram). OSWA, 1 session per week of acupuncture; TSWA, 3 sessions per week of
acupuncture.
Table 3
Response rates during the entire study*.
Variable TSWA group (n 5 30) OSWA group (n 5 30) Difference (95% CI) P†
Response rate, %
Week 4 58.0 13.3 44.7 (23.2 to 66.1) 0.001
Week 8 64.7 50.0 14.7 (210.1 to 39.4) 0.435
Week 16 60.7 14.7 46.0 (24.4 to 67.6) ,0.001
* Missing data were imputed using multiple imputations.
† Calculated using the x2 test. Appendix Table 1, http://links.lww.com/PAIN/B60 shows detailed information on imputed data sets.
OSWA, 1 session per week of acupuncture; TSWA, 3 sessions per week of acupuncture.
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in the TSWA group. Of note, the frequency in our study is higher
than that of Witt C’s. This did not mean the higher frequency did
not achieve better effect. It may be that, inWitt C’s trial, the routine
use of analgesics was permitted and themean dayswith intake of
analgesics ranged from 0.9 to 1.4 days per week. However, our
study reported that no participant used analgesics and drug-
related adverse events were avoidable. Another study by Scharf
et al. of acupuncture 1 or 2 session/week for 11 weeks reported
that 51.5% of participants achieved$36% decrease in WOMAC
score after treatment.22 The result was incongruent with our
study, which showed 63.3% responders (cutoff: 36%decrease in
Figure 2. Response rates during the study. Vertical bars represent 95%
confidence interval. *P , 0.05. OSWA, 1 session per week of acupuncture;
TSWA, 3 sessions per week of acupuncture.
Table 4
Outcomes and differences between groups using nonimputed data.
Variable TSWA group OSWA group Mean difference (95% CI) P
NRS (0-10)
Week 4 4.3 (1.5) 5.2 (1.3) 20.8 (21.6 to 20.1) ,0.001
Week 8 3.8 (1.5) 4.1 (1.6) 20.3 (21.2 to 0.6)
Week 16 3.6 (1.7) 5.1 (1.3) 21.5 (22.4 to 20.7)
WOMAC pain (0-20)
Week 4 5.0 (2.8) 5.1 (1.8) 20.1 (21.4 to 1.1) 0.061
Week 8 4.0 (2.4) 3.5 (1.5) 0.5 (20.7 to 1.7)
Week 16 4.0 (2.6) 5.7 (1.6) 21.6 (22.8 to 20.4)
WOMAC function (0-68)
Week 4 17.6 (7.6) 22.3 (6.2) 24.7 (28.5 to 20.9) ,0.001
Week 8 14.5 (8.3) 17.5 (6.9) 23.0 (27.4 to 1.4)
Week 16 14.5 (8.5) 23.8 (5.4) 29.3 (213.3 to 25.2)
WOMAC stiffness (0-8)
Week 4 2.1 (1.1) 2.4 (1.1) 20.3 (20.9 to 0.3) 0.101
Week 8 1.8 (1.2) 2.0 (1.1) 20.2 (20.9 to 0.4)
Week 16 1.8 (0.9) 2.5 (1.1) 20.7 (21.3 to 20.1)
Physical health (SF-12)* (0-100)
Week 4 32.6 (8.4) 30.0 (6.2) 2.6 (21.5 to 6.6) 0.078
Week 8 32.2 (8.2) 35.2 (8.7) 23.0 (27.8 to 1.8)
Week 16 37.8 (9.7) 29.4 (6.2) 8.4 (3.8 to 13.0)
Mental health (SF-12)* (0-100)
Week 4 50.0 (11.0) 52.9 (8.0) 22.9 (28.1 to 2.3) 0.609
Week 8 53 (10.6) 54.8 (5.7) 21.8 (26.6 to 3.0)
Week 16 55.5 (7.3) 53.3 (8.0) 2.3 (22.0 to 6.6)
Patient global assessment (0-4)*, median (IQR)
Week 4 2.0 (1.0, 2.0) 1.0 (1.0, 1.0) — ,0.001†
Week 8 1.5 (1.0, 2.3) 2.0 (1.0, 2.0) — 0.801†
Week 16 2.0 (1.0, 3.0) 1.0 (1.0, 1.0) — ,0.001†
Credibility of treatment rating scale (3-37)*,
median (IQR)
After the first treatment 19.0 (16.0, 23.5) 19.0 (17.8, 25.0) — 0.716†
Values are mean values (SDs) unless stated otherwise.
* Higher values indicate better status.
† Calculated using the Wilcoxon rank-sum test.
CI, confidence interval; IQR, interquartile range; NRS, numerical rating scale; OSWA, 1 session per week of acupuncture; SF-12, Medical Outcomes Study 12-item Short-Form Health Survey; TSWA, 3 sessions perweek of
acupuncture; WOMAC, Western Ontario and McMasters Universities Osteoarthritis Index.
Figure 3. NRS scores during the study. Vertical bars represent SD. NRS,
numerical rating scale; OSWA, 1 session per week of acupuncture; TSWA, 3
sessions per week of acupuncture.
Copyright © 2020 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
2536 L.-L. Lin et al.·161 (2020) 2532–2538 PAIN®
WOMAC score) in the OSWA group. We speculate that the
inconsistency was attributed to the use of electrostimulation. A
manual acupuncture was used in Scharf’s study; however,
electroacupuncture—a more continuous and powerful
approach4—was used in this study.
Our study has several limitations. First, the participants were
not blinded. It is difficult to exclude the placebo effects from the
participants who received TSWA comparing to those who only
received OSWA. In the future, participants in the OSWA group
could receive the same 3 treatments per week but only one of
them is a real acupuncture treatment and the other 2 are sham
acupuncture treatments. This will blind the participants and
minimize the placebo effect. Second, although semistandard
prescription is the distinguishing feature of traditional acupunc-
ture treatment and often used in many large trials,12,22,31 it might
be a confounder and makes the outcome difficult to control.
Third, longer-term follow-up has not been assessed. Further
research should measure longer-term outcomes for different
treatment frequencies. Finally, we only use 2 frequencies, which
seem not enough to explore the relationship between frequency
and effect. Future studies may need $3 frequencies to
investigate the optimal frequency of acupuncture for KOA.
In conclusions, compared with the OSWA group, the TSWA
group manifested persisting superiority for $16 weeks in KOA
treatment, including relieving pain and dysfunction. It is feasible to
conduct a large trial of different acupuncture treatment frequency
for patients with KOA and the data of the study can lead to an
estimate of the sample size. A future trial will aim to definitely
investigate the optimal frequency of acupuncture for KOA to
produce the evidence to facilitate clinical choice in routine
practice.
Conflict of interest statement
All authors have completed the ICMJE uniform disclosure and
declare support for the submitted work. The authors have
declared no conflicts of interest.
Acknowledgements
The authors thank the researcher Y. Wang who contributed by
designing the randomization sequence andBeijingGuide Technology
Company for its technical support.ThisworkwassupportedbyBeijing
Municipal Administration of Hospitals Clinical Medicine Development
of Special Funding Support [XMLX201607] and Beijing Municipal
Science & Technology Commission [D171100003217003]. The
funders had no role in the study other than to provide funding.
Beijing Hospital of Traditional Chinese Medicine is affiliated with
Capital Medical University. Patient informed consent will be
obtained.
Author contributions: Study concept and design: C.-Z. Liu, L.-L. Lin,
and J.-F. Tu. Acquisition, analysis, or interpretation of data: C.-Z. Liu,
L.-Q. Wang, L.-L. Lin, J.-F. Tu, G.-X. Shi, J.-K. Shao, J.-L. Li, and
N. Zhang. Drafting of the manuscript: L.-L. Lin, J.-W. Yang,
L.-Q. Wang, and X. Zou. Critical revision of the manuscript for
important intellectual content: J.-W. Yang and L.-Q. Wang.
Obtaining of funding: C.-Z. Liu. Study supervision: C.-Z. Liu.
Appendix A. Supplemental digital content
Supplemental digital content associated with this article can be
found online at http://links.lww.com/PAIN/B60.
Article history:
Received 5 January 2020
Received in revised form 21 May 2020
Accepted 22 May 2020
Available online 29 May 2020
References
[1] Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW.
Validation study of WOMAC: a health status instrument for measuring
clinically important patient relevant outcomes to antirheumatic drug
therapy in patients with osteoarthritis of the hip or knee. J Rheumatol
1988;15:1833–40.
[2] Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC.
Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the
knee: a randomized, controlled trial. Ann Intern Med 2004;141:901–10.
[3] Chen L, Michalsen A. Management of chronic pain using complementary
and integrative medicine. BMJ 2017;357:j1284.
[4] Chen N, Wang J, Mucelli A, Zhang X, Wang C. Electro-acupuncture is
beneficial for knee osteoarthritis: the evidence from meta-analysis of
randomized controlled trials. Am J Chin Med 2017;45:965–85.
[5] Chen YJ, Chen CT, Liu JY, Shimizu Bassi G, Yang YQ. What is the
appropriate acupuncture treatment schedule for chronic pain? Review
and analysis of randomized controlled trials. Evid Based Complement
Alternat Med 2019;2019:5281039.
[6] Dai Z, Liu HS, Wang SJ, Bai W, Yang JY, Li H, Sun Y, Liu Q. Efficacy
analysis on patients with knee osteoarthritis accepting acupuncture
treatment with different frequencies. Liaoning J Traditional Chin Med
2014;41:1496–8.
[7] Ezzo J, Berman B, Hadhazy VA, Jadad AR, Lao L, Singh BB. Is
acupuncture effective for the treatment of chronic pain? A systematic
review. PAIN 2000;86:217–25.
Figure 4. WOMAC function scores during the study. Vertical bars represent
SD.OSWA, 1 session per week of acupuncture; TSWA, 3 sessions per week of
acupuncture; WOMAC, Western Ontario and McMasters Universities Oste-
oarthritis Index.
Figure 5. WOMAC pain scores during study. Vertical bars represent SD.
OSWA, 1 session per week of acupuncture; TSWA, 3 sessions per week of
acupuncture; WOMAC, Western Ontario and McMasters Universities Oste-
oarthritis Index.
Copyright © 2020 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
November 2020·Volume 161·Number 11 www.painjournalonline.com 2537
http://links.lww.com/PAIN/B60
www.painjournalonline.com
[8] Foster NE, Thomas E, Barlas P, Hill JC, Young J, Mason E, Hay EM.
Acupuncture as an adjunct to exercise based physiotherapy for
osteoarthritis of the knee: randomised controlled trial. BMJ 2007;335:
436.
[9] Gao SZ. Science of acupuncture and moxibustion therapy. Shanghai:
Shanghai Scientific and Technical Publishers, 2009.
[10] Geenen R, Overman CL, Christensen R, Asenlof P, Capela S,
Huisinga KL, Husebo MEP, Koke AJA, Paskins Z, Pitsillidou IA,
Savel C, Austin J, Hassett AL, Severijns G, Stoffer-Marx M, Vlaeyen
JWS, Fernandez-de-Las-Penas C, Ryan SJ, Bergman S. EULAR
recommendations for the health professional’s approach to pain
management in inflammatory arthritis and osteoarthritis. Ann Rheum
Dis 2018;77:797–807.
[11] Global, regional, and national incidence, prevalence, and years lived with
disability for 310 diseases and injuries, 1990-2015: a systematic analysis
for the Global Burden of Disease Study 2015. Lancet 2016;388:
1545–602.
[12] Hinman RS, McCrory P, Pirotta M, Relf I, Forbes A, Crossley KM,
Williamson E, Kyriakides M, Novy K, Metcalf BR, Harris A, Reddy P,
Conaghan PG, Bennell KL. Acupuncture for chronic knee pain:
a randomized clinical trial. JAMA 2014;312:1313–22.
[13] Hochberg MC, Altman RD, Brandt KD, Clark BM, Dieppe PA, Griffin MR,
Moskowitz RW, Schnitzer TJ. Guidelines for the medical management of
osteoarthritis. Part II. Osteoarthritis of the knee. American College of
Rheumatology. Arthritis Rheum 1995;38:1541–6.
[14] Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet 2019;393:1745–59.
[15] Jensen MP, Karoly P, Braver S. The measurement of clinical pain
intensity: a comparison of six methods. PAIN 1986;27:117–26.
[16] Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis.
Ann Rheum Dis 1957;16:494–502.
[17] Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J,
Callahan L, Copenhaver C, Dodge C, Felson D, Gellar K, Harvey WF,
HawkerG, Herzig E, KwohCK, Nelson AE, Samuels J, Scanzello C,White
D, Wise B, Altman RD, DiRenzo D, Fontanarosa J, GiradiG, Ishimori M,
Misra D, Shah AA, Shmagel AK, Thoma LM, Turgunbaev M, Turner AS,
Reston J. 2019 American college of rheumatology/arthritis foundation
guideline for the management of osteoarthritis of the hand, hip, and knee.
Arthritis Rheumatol 2020;72:220–33.
[18] Lin LL, Tu JF, Shao JK, Zou X, Wang TQ, Wang LQ, Yang JW, Sun N, Liu
CZ. Acupuncture of different treatment frequency in knee osteoarthritis:
a protocol for a pilot randomized clinical trial. Trials 2019;20:423.
[19] MacPherson H, Thomas K, Walters S, Fitter M. A prospective survey of
adverse events and treatment reactions following 34,000 consultations
with professional acupuncturists. Acupunct Med 2001;19:93–102.
[20] MacPherson H, Maschino AC, Lewith G, Foster NE, Witt CM, Vickers AJ.
Characteristics of acupuncture treatment associated with outcome: an
individual patient meta-analysis of 17,922 patients with chronic pain in
randomised controlled trials. PloS one 2013;8:e77438.
[21] MacPherson H, Vertosick EA, Foster NE, Lewith G, Linde K, Sherman KJ,
Witt CM, Vickers AJ. The persistence of the effects of acupuncture after
a course of treatment: a meta-analysis of patients with chronic pain. PAIN
2017;158:784–93.
[22] Scharf HP, Mansmann U, Streitberger K, Witte S, Kramer J, Maier C,
Trampisch HJ, Victor N. Acupuncture and knee osteoarthritis: a three-
armed randomized trial. Ann Intern Med 2006;145:12–20.
[23] Sun N, Tu JF, Lin LL, Li YT, Yang JW, Shi GX, Lao LX, Liu CZ. Correlation
between acupuncture dose and effectiveness in the treatment of knee
osteoarthritis: a systematic review. Acupunct Med 2019;37:261–7.
[24] Tang X, Wang S, Zhan S, Niu J, Tao K, Zhang Y, Lin J. The prevalence of
symptomatic knee osteoarthritis in China: results from the China health
and retirement longitudinal study. Arthritis Rheumatol 2016;68:648–53.
[25] Vickers AJ, Vertosick EA, Lewith G, MacPherson H, Foster NE, Sherman
KJ, Irnich D,Witt CM, Linde K. Acupuncture for chronic pain: update of an
individual patient data meta-analysis. J Pain 2018;19:455–74.
[26] Vincent C, Lewith G. Placebo controls for acupuncture studies. J R Soc
Med 1995;88:199–202.
[27] WangTQ, Li YT,Wang LQ,ShiGX, TuJF, YangJW,HouYQ, Lin LL, SunN,
Zhao JJ, Hou HK, Liu CZ. Electroacupuncture versus manual acupuncture
for knee osteoarthritis: a randomized controlled pilot trial. Acupunct Med
2020. doi: 10.1177/0964528419900781 [epub ahead of print].
[28] Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey:
construction of scales and preliminary tests of reliability and validity. Med
Care 1996;34:220–33.
[29] White A, Hayhoe S, Hart A, Ernst E. Adverse events following
acupuncture: prospective survey of 32 000 consultations with doctors
and physiotherapists. BMJ 2001;323:485–6.
[30] White P, Bishop FL, Prescott P, Scott C, Little P, Lewith G. Practice,
practitioner, or placebo? A multifactorial, mixed-methods randomized
controlled trial of acupuncture. PAIN 2012;153:455–62.
[31] Witt C, Brinkhaus B, Jena S, Linde K, Streng A,Wagenpfeil S, Hummelsberger
J, Walther HU, Melchart D, Willich SN. Acupuncture in patients with
osteoarthritis of the knee: a randomised trial. Lancet 2005;366:136–43.
Copyright © 2020 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
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