Acupuncture in Patients With Osteoarthritis of The Knee: A Randomised Trial
Acupuncture in Patients With Osteoarthritis of The Knee: A Randomised Trial
Acupuncture in Patients With Osteoarthritis of The Knee: A Randomised Trial
Summary
Lancet 2005; 366: 13643
See Comment page 100
Institute of Social Medicine,
Epidemiology, and Health
Economics (C Witt MD,
B Brinkhaus MD, S Jena MSc,
Prof S N Willich MD) and Centre
for Musculoskeletal Surgery
(H U Walther MD), Charit
University Medical Centre,
Berlin, Germany; Centre for
Complementary Medicine
Research, Department of
Internal Medicine II (K Linde MD,
A Streng PhD, D Melchart MD)
and Institute of Medical
Statistics and Epidemiology
(S Wagenpfeil PhD), Technische
Universitt Mnchen, Munich,
Germany; Division of
Complementary Medicine,
Department of Internal
Medicine, University Hospital
Zurich, Zurich, Switzerland
(D Melchart MD); and
International Society for
Chinese Medicine, Societas
Medicinae Sinensis, Munich,
Germany (J Hummelsberger MD)
Correspondence to:
Dr Claudia Witt, Institute of
Social Medicine, Epidemiology,
and Health Economics, Charit
University Medical Centre,
10098 Berlin, Germany
claudia.witt@charite.de
Background Acupuncture is widely used by patients with chronic pain although there is little evidence of its
effectiveness. We investigated the efcacy of acupuncture compared with minimal acupuncture and with no
acupuncture in patients with osteoarthritis of the knee.
Methods Patients with chronic osteoarthritis of the knee (Kellgren grade 2) were randomly assigned to
acupuncture (n=150), minimal acupuncture (supercial needling at non-acupuncture points; n=76), or a waiting list
control (n=74). Specialised physicians, in 28 outpatient centres, administered acupuncture and minimal
acupuncture in 12 sessions over 8 weeks. Patients completed standard questionnaires at baseline and after 8 weeks,
26 weeks, and 52 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis
(WOMAC) index at the end of week 8 (adjusted for baseline score). All main analyses were by intention to treat.
Results 294 patients were enrolled from March 6, 2002, to January 17, 2003; eight patients were lost to follow-up after
randomisation, but were included in the nal analysis. The mean baseline-adjusted WOMAC index at week 8 was
269 (SE 14) in the acupuncture group, 358 (19) in the minimal acupuncture group, and 496 (20) in the waiting
list group (treatment difference acupuncture vs minimal acupuncture 88, [95% CI 135 to 42], p=00002;
acupuncture vs waiting list 227 [275 to 179], p00001). After 52 weeks the difference between the
acupuncture and minimal acupuncture groups was no longer signicant (p=008).
Interpretation After 8 weeks of treatment, pain and joint function are improved more with acupuncture than with
minimal acupuncture or no acupuncture in patients with osteoarthritis of the knee. However, this benet decreases
over time.
Introduction
Osteoarthritis most frequently affects the knee joint.1
Anti-inammatory drugs used to treat the symptoms of
this disorder are associated with various side-effects.2
Furthermore, for patients for whom these drugs do not
lead to an adequate response, replacement surgery is
often recommended.3 Patients with chronic pain are
increasingly using acupuncture for pain relief.4 There is
some evidence that acupuncture can be effective in
treating pain and dysfunction in patients with
osteoarthritis of the knee. In a systematic review
including seven randomised controlled trials with a total
of 393 patients, acupuncture was more effective than
sham acupuncture in reducing pain, whereas for joint
function the results were inconclusive.5 These previous
studies, however, were based on small sample sizes and
the follow-up period was never longer than 3 months.
We aimed to investigate the efcacy of acupuncture
compared with minimal acupuncture and with no
acupuncture in patients with pain and dysfunction due
to osteoarthritis of the knee.
Methods
Patients
Patients were included in our study if they were aged
5075 years, had been diagnosed with osteoarthritis
according to the American College of Rheumatology
criteria, had documented radiological alterations in the
136
knee joint of grade 2 or more according to KellgrenLawrence criteria,6,7 had an average pain intensity of 40 or
more on a 100 mm visual analogue scale in the 7 days
before baseline assessment, and if they gave written
informed consent. The exclusion criteria were one or
more of the following: pain in the knee caused by
inammatory, malignant, or autoimmune disease; or
other reasons for pain in the knee, such as serious
valgus-defective or varus-defective position. Patients
were also excluded if they had had knee surgery,
arthroscopy of the affected knee in the past year,
chondroprotective or intra-articular injection in the past
4 months, systemic corticoid treatment or beginning of a
new treatment for osteoarthritis in the past 4 weeks, local
antiphlogistic treatment, acupuncture treatment during
the past 12 months, or physiotherapy or other treatments
for osteoarthritis knee pain (with the exception of nonsteroidal anti-inammatory drugs) during the previous
4 weeks. Additional exclusion criteria were application
for pension or disability benets, serious acute or
chronic organic disease or mental disorder, pregnancy or
breastfeeding, and blood coagulation disorders or
coagulation-inhibiting medication other than aspirin.
Most participants were recruited through reports in local
newspapers; a few patients spontaneously contacted trial
centres. All study participants provided written informed
consent and were insured according to the German law
for medical products.
www.thelancet.com Vol 366 July 9, 2005
Articles
Procedures
Figure 1 shows the study design. Patients were
randomly assigned to a treatment group stratied by
centre in a 2: 1: 1 ratio (acupuncture: minimal
acupuncture: waiting list) with a centralised telephone
randomisation procedure (random list generated with
Samp Size 20). The 2: 1: 1 ratio was used to help with
recruitment and increase the compliance of trial
physicians. Minimal acupuncture served as a sham
intervention; the additional no acupuncture waiting list
control was included since minimal acupuncture might
not be a physiologically inert placebo. Patients in the
acupuncture and minimal acupuncture groups were
unaware of their treatment allocation. The total followup study period per patient was 52 weeks. The study was
undertaken according to common guidelines for clinical
trials (Declaration of Helsinki, ICH-GCP including
certication by an external audit). The study protocol
was approved by the appropriate ethics review boards
and has been described in detail elsewhere.8
Study interventions were developed in a consensus
process with acupuncture experts and societies, and
provided by physicians who were trained (at least 140 h)
and experienced in acupuncture. Both the acupuncture
and minimal acupuncture treatments consisted of
12 sessions of 30 min duration, administered over
8 weeks (usually two sessions per week for the rst
4 weeks, followed by one session per week in the
remaining 4 weeks). For patients with bilateral
osteoarthritis in the acupuncture and the minimal
acupuncture groups, both knees were needled with at
least eight out of ten proposed points (at least 16 needles
altogether), whereas for patients with unilateral
osteoarthritis, the physician was able to choose
unilateral or bilateral acupuncture. For unilateral
acupuncture, the treatment had to be done with at least
eight needles. Patients in the waiting list group did not
receive acupuncture treatment for a period of 8 weeks,
after which time they then also received acupuncture.
Acupuncture treatment was semi-standardised: all
patients were treated with a selection of local and distant
points chosen by the acupuncturists according to the
principles of traditional Chinese medicine. Additional
points included body acupuncture points, ear acupuncture
points, and trigger points. Patients were treated by use of
at least six local acupuncture points from the following
selection:9 stomach 34, 35, 36; spleen 9, 10; bladder 40;
kidney 10; gall bladder 33, 34; liver 8; extraordinary points
Heding, Xiyan. Additionally, physicians selected and
needled at least two distant points from the following
selection: spleen 4, 5, 6; stomach 6; bladder 20, 57, 58, 60,
62; kidney 3. Sterile disposable one-time needles had to be
used, but physicians were able to choose the needle length
and diameter. Physicians were instructed to achieve de qi
(an irradiating feeling deemed to indicate effective
needling) if possible, and needles were stimulated
manually at least once during each session.
www.thelancet.com Vol 366 July 9, 2005
Randomisation
Acupuncture
12 sessions
Follow-up
Minimal acupuncture
12 sessions
Follow-up
Acupuncture
12 sessions
Patients
Baseline
assessment
Physicians
Follow-up
assessment
Follow-up
Follow-up
assessment
Follow-up
assessment
Medical status
Treatment documentation
0
26
52
Week
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Articles
Statistical analysis
300 randomised
150 allocated
acupuncture
1 without baseline
and acupuncture
3 lost to follow-up
after randomisation
76 allocated minimal
acupuncture
1 without baseline
and acupuncture
2 lost to follow-up
after randomisation
74 allocated
waiting list
4 without baseline
3 lost to follow-up
after randomisation
146 followed up at
8 weeks
73 followed up at
8 weeks
146 followed up at
26 weeks
73 followed up at
26 weeks
67 followed up at
8 weeks
2 lost to follow-up
after week 26
146 followed up at
52 weeks
71 followed up at
52 weeks
3 lost to follow-up/
missing MOM data
67 in main ITT efficacy analysis
9 violation of
treatment protocol
9 other protocol
deviations
49 in PP analysis
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Articles
Women
Men
Age (years)
Body-mass index
10 years of school
Kellgren criteria
Kellgren 0
Kellgren 1
Kellgren 2
Kellgren 3
Kellgren 4
Duration of disease (years)
Days per month with pain
Osteoarthritis bilateral
Previous treatment
Pharmaceutical intervention
(past 6 months)
Physiotherapy (past 6 months)
Previous acupuncture treatment
Average pain (VAS)
WOMAC Index
Disability (PDI)
Physical health (SF-36)*
Mental health (SF-36)*
Pain affective (SES, t standard scores)
Pain sensoric (SES, t standard scores)
Depression (ADS, t standard scores)
Total (n=294)
Acupuncture (n=149)
195 (66%)
99 (34%)
640 (65)
290 (50)
43 (16%)
105 (70%)
44 (30%)
645 (64)
295 (48)
16 (11%)
49 (65%)
26 (35%)
634 (66)
288 (46)
11 (17%)
41 (59%)
29 (41%)
636 (67)
283 (589)
16 (24%)
1 (03%)
15 (5%)
121 (41%)
120 (41%)
37 (13%)
92 (79)
262 (65)
224 (76%)
0
6 (4%)
52 (35%)
66 (44%)
25 (17%)
91 (85)
262 (65)
110 (74%)
0
5 (7%)
29 (39%)
32 (43%)
9 (12%)
99 (76)
266 (64)
58 (77%)
1 (1%)
4 (6%)
40 (57%)
22 (31%)
3 (4%)
88 (68)
257 (68)
56 (80%)
97 (33%)
43 (29%)
27 (36%)
27 (39%)
45 (15%)
23 (8%)
653 (145)
514 (187)
280 (132)
297 (77)
513 (120)
489 (91)
527 (99)
512 (94)
22 (15%)
14 (9%)
649 (142)
508 (188)
279 (142)
300 (74)
518 (121)
488 (93)
524 (95)
512 (100)
7 (9%)
5 (7%)
685 (144)
525 (186)
278 (132)
292 (82)
511 (116)
492 (87)
541 (108)
513 (79)
16 (23%)
4 (6%)
628 (150)
516 (188)
283 (113)
298 (79)
506 (121)
488 (93)
520 (100)
512 (94)
Data are number (%) or mean (SD). WOMAC=questionnaire for assessing pain, function and stiffness due to osteoarthritis (Western Ontario and McMasters Universities Osteoarthritis
Index); VAS=visual analogue scale; PDI=pain disability index; SF-36=MOS 36-item short-form quality-of-life questionnaire; SES=questionnaire for assessing the emotional aspects of pain
(Schmerzempndungsskala); ADS=depression scale (Allgemeine Depressionsskala). *Higher values indicate better status.
Minimal
p
acupuncture
n=148
52 (11)
55 (10)
50 (13)
56 (09)
n=73
51 (09)
56 (07)
48 (13)
57 (06)
n=146
96 (66%)
9 (6%)
41 (28%)
n=71
40 (56%)
4 (6%)
27 (38%)
0860
0384
0327
0601
Results
Between March 6, 2002, and January 17, 2003, about
1100 patients with osteoarthritis of the knee applied to
100
90
Acupuncture
Minimal acupuncture
Waiting list
80
70
60
50
40
30
20
10
0332
Rating scale based on 0=minimum and 6=maximum agreement; data are number (%)
or mean (SD).
all the data in the study and had nal responsibility for
the decision to submit for publication.
WOMAC index
0
0
26
52
146
72
64
146
71
62
Week
149
Acupuncture
Minimal acupuncture 75
70
Waiting list
145
73
67
Figure 3: Development of the mean WOMAC Index in the three treatment groups
Vertical bars represent standard errors.
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Articles
Acupuncture
WOMAC at baseline
100
Minimal acupuncture
100
90
90
90
80
80
80
70
70
70
60
60
60
50
50
50
40
40
40
30
30
30
20
20
20
10
10
10
0
0
10 20 30 40 50 60 70 80 90 100
Waiting list
100
0
0
10 20 30 40 50 60 70 80 90 100
WOMAC at week 8
WOMAC at week 8
10 20 30 40 50 60 70 80 90 100
WOMAC at week 8
Waiting list
mean (SE)
Acupuncture vs
waiting list * (95%CI)
0001
0001
0003
0001
0001
0003
0137
0134
0494
0725
0059
0001
0001
0001
0001
0001
0001
0016
0003
0044
0250
0001
21 (28 to 14)
13 (30 to 03)
0001
0110
269 (14)
244 (14)
327 (19)
270 (14)
164 (09)
362 (06)
536 (07)
424 (07)
473 (07)
479 (08)
163 (15)
358 (19)
332 (20)
423 (27)
358 (20)
222 (12)
331 (08)
519 (10)
441 (09)
481 (10)
483 (11)
213 (21)
496 (20)
449 (21)
550 (28)
504 (21)
274 (13)
318 (09)
507 (10)
459 (10)
498 (10)
494 (11)
274 (22)
88 (135 to 42)
88 (137 to 39)
96 (160 to 32)
89 (137 to 40)
58 (88 to 28)
31 (11 to 51)
17 (06 to 40)
17 (39 to 05)
08 (32 to 16)
05 (31 to 21)
49 (101 to 02)
44 (02)
45 (05)
53 (03)
46 (06)
64 (03)
58 (07)
10 (16 to 03)
01 (16 to 15)
0005
0922
WOMAC=questionnaire for assessing pain, function, and stiffness due to osteoarthritis (Western Ontario and McMasters Universities Osteoarthritis Index); PDI=pain disability index; SF-36=MOS 36-item short-form quality-oflife questionnaire; SES=questionnaire for assessing the emotional aspects of pain (Schmerzempndungsskala); ADS=depression scale (Allgemeine Depressionsskala). *Mean baseline-adjusted treatment difference between
groups. Higher values indicate better status
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Articles
At 26 weeks
Questionnaire
WOMAC Index
WOMAC Pain
WOMAC Stiffness
WOMAC Physical function
Disability (PDI)
Physical health (SF36)
Mental health (SF36)
Pain affective (SES, t standard scores)
Pain sensoric (SES, t standard scores)
Depression (ADS, t standard scores)
Days with limited function
At 52 weeks
Acupuncture
mean (SD)
Minimal acupuncture
mean (SD)
Acupuncture vs minimal
acupuncture* (95%CI)
Acupuncture
mean (SD)
304 (213)
289 (227)
347 (253)
304 (214)
186 (130)
351 (88)
526 (115)
413 (93)
460 (92)
482 (99)
418 (456)
363 (223)
338 (223)
403 (261)
365 (232)
228 (153)
330 (100)
517 (112)
434 (94)
480 (93)
487 (93)
611 (617)
58 (120 to 03)
48 (112 to 16)
56 (128 to 17)
62 (124 to 01)
42 (83 to 00)
21 (05 to 48)
09 (23 to 42)
21 (48 to 06)
20 (46 to 06)
05 (36 to 25)
194 (355 to 32)
0063
0137
0131
0053
0048
0111
0580
0120
0138
0730
0019
327 (224)
300 (235)
374 (252)
330 (230)
200 (140)
350 (100)
529 (110)
425 (102)
477 (113)
486 (102)
411 (565)
384 (226)
335 (213)
471 (280)
389 (238)
236 (150)
328 (95)
511 (117)
441 (104)
484 (105)
498 (101)
678 (717)
0080
0285
0011
0081
0089
0120
0254
0291
0643
0430
0007
57 (121 to 07)
35 (100 to 30)
97 (171 to 22)
59 (125 to 07)
36 (77 to 05)
22 (06 to 51)
19 (13 to 51)
16 (46 to 14)
07 (39 to 24)
12 (43 to 18)
267 (460 to 75)
WOMAC=Western Ontario and McMasters Universities Osteoarthritis Index; PDI=pain disability index; SF-36=MOS 36-item short-form quality-of-life questionnaire; SES=Schmerzempndungsskala; ADS=Allgemeine
Depressionsskala. *Mean difference between groups; minor discrepancies between differences calculated from group means presented in the table are due to rounding. Higher values indicate better status.
Discussion
In this study, patients with osteoarthritis of the knee
who received acupuncture had signicantly less pain
and better function after 8 weeks than did patients who
received minimal acupuncture or no acupuncture. After
26 and 52 weeks, exploratory analysis indicated that the
differences between acupuncture and minimal
acupuncture were no longer signicant.
The present study is, to date, one of the largest and
most rigorous trials of the efcacy of acupuncture
available. Its strengths include a prepublished protocol,8
interventions based on expert consensus by qualied
and experienced medical acupuncturists, assessment of
the credibility of interventions, outcome measurements
as recommended in guidelines for trials on
osteoarthritis,20,21 and very high follow-up rates. One
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