One-hundred and sixteen patients (mean age 62.4 years, range = 40–83, 33% males) with chronic osteoarthritis of the knee completed the study between April 2004 and May 2005. displays the patient recruitment, allocation, losses to followup, and exclusions. Randomisation resulted in a similar distribution of gender, premedication, and disease severity across the allocation for the first treatment modality ().
Patient recruitment, randomisation and followup.
Knee flexibility improved by 10 degrees or more immediately after the acupuncture procedure in 75 of 116 classical acupuncture sessions, giving rise to a number needed to treat (NNT) of 1.5 (95% confidence interval 1.4 to 1.8); this compared to 41 of 116 modern acupuncture sessions (NNT = 2.9, 95% CI 2.2 to 3.8) and to 6 of 116 non-specific needling sessions (NNT = 19, 95% CI 9.2 to 53, P < 0.001). Classical acupuncture resulted in a significantly larger improvement immediately after the treatment (, mean change = 10.3 degrees, 95% CI 8.9 to 12) compared to modern acupuncture (4.7 degrees, 95% CI 3.6 to 5.8), while no effect was observed for non-specific needling (0.34 degrees, 95% CI—0.61 to 1.3; F = 27.3; df = 3.1, 358; P < 0.001). Adjusting for the Kellgren classification revealed that the difference between classical acupuncture and modern acupuncture was even larger in patients with more severe illness (P = 0.02).
Figure 2 Knee flexion before and after acupuncture. The figure compares the maximum possible knee movement until further flexion was blocked by pain for classical acupuncture, semistandardised modern acupuncture, and non-specific needling. Flexion was assessed (more ...)
The analysis of the change scores employing multilevel modelling revealed significant carry-over effects from the first to the second and from the second to the third treatment. When the first treatment consisted of classical acupuncture (estimated mean change = 9.1 degrees, 95% CI 6.2 to 13), the effects from modern acupuncture (mean change = 0.7 degrees, 95% CI—1.3 to 2.7) were negligible. However, when the first treatment consisted of modern acupuncture (mean change = 5.5 degrees, 95% CI 3.1 to 7.9), subsequent classical acupuncture resulted in a further flexibility gain (mean change = 4.3 degrees, 95% CI 2.0 to 6.6). The small differences from the values reported in the preceding paragraph arise from the adjustment for carry-over effects.
The multilevel model also suggests that the substantial variation between patients in the effects of classical acupuncture is relatively independent of the variation in the effect of modern acupuncture—in other words, the extent of improvement after classical acupuncture is not correlated with the extent of improvement after modern acupuncture (P = 0.43 for the covariance in the random part of the model).
In contrast to the differences in efficacy for knee mobility, all three treatment forms resulted in some immediate improvement of pain scores (). Classical acupuncture showed a significantly larger improvement immediately after treatment than non-specific needling did (post-hoc contrast, F = 5.4, df = 1, P = 0.022). Success rates defined as a WOMAC reduction by 50% were the largest immediately after classical acupuncture (85 of 116, NNT 1.4, 95% CI 1.23–1.56) as compared to modern acupuncture (74 of 116, NNT 1.56, 95% CI 1.38 to 1.84, nonsignificant difference) and non-specific needling (56 of 116, NNT 2.1, 95% CI 1.68–2.46, P = 0.02). The pain relieving effect of any needling rapidly declined. At the 7-day follow-up visit, pain scores were similar across the three methods ().
Figure 3 WOMAC pain scores before and after acupuncture. The figure compares the WOMAC pain scores for classical acupuncture, semistandardised modern acupuncture, and non-specific needling. Pain was assessed immediately prior to acupuncture, directly thereafter, (more ...)
3.1. Strengths and Weaknesses
The strength of the present study is its use of a novel study design for acupuncture which establishes blinding of both patients and the treating physicians. This design overcame major shortcomings of previous studies which failed to achieve adequate blinding and in which sham treatment usually differed substantially from acupuncture. The results of the present study offer an answer to the basic question of whether the effects in acupuncture are specific or caused by mere skin penetration. In our study, the needle location remained the only difference between the three treatment modalities, approximating for the first time the principles of randomised and double-blinded, controlled trials in acupuncture studies.
116 patients with osteoarthritis of the knee received three treatments in a random order: acupuncture according to an individualised diagnosis of Chinese medicine (classical acupuncture), a semistandardised modern version of acupuncture usually employed in acupuncture trials (modern acupuncture) and non-specific needling. The main findings were a twice as large improvement in knee flexibility immediately after classical acupuncture (10.3 degrees) as compared to modern acupuncture (4.7 degrees) and no change after non-specific needling (0.3 degrees). The largest improvements in pain were also seen immediately after classical acupuncture (a WOMAC score reduction by 50% or more in 85 of 116 patients); however, non-specific needling also achieved considerable effects (core reduction by 50% in 56 of 116 patients, approaching two-thirds of the maximum effect observed after classical acupuncture. Therefore, the present data suggest substantial non-specific effects in subjective pain relief. In contrast to subjective pain relief, however, improvements in knee flexibility as objective outcome measure were only seen after the needling of specifically selected points and not after non-specific sham needling. To our understanding, this is the first study to prove specific effects of acupuncture and the first to exclude bias caused by differences in the control arms.
With respect to pain relief, the present study corroborates earlier findings. The measure of effect observed for the sham acupuncture as well as for the semistandardised modern acupuncture was similar to those previously observed in multicentre trials. Pain relief of comparable effect can also be achieved by other methods such as transcutaneous electrical nerve stimulation, supporting the notion that neurogenic pain contributes to the symptoms in patients with degenerative changes in joints [32
]. However, the non-specific effects of acupuncture may exceed those of mere placebo effects [34
], for reasons as yet unexplained.
Interestingly after seven days, no relevant difference in pain scale was reported, although we found the significant changes in knee motility to be persistent among the three treatment groups. This gain in function (knee flexibility) may be considered an indirect measure of pain relief as pain is the main limiting factor for knee motility.
Moreover, we observed a rapid improvement of knee flexibility immediately after classical acupuncture, which was twice the effect observed after modern acupuncture and absent after non-specific needling. Elucidating the physiological mechanisms [35
] underlying this method-specific difference in effect was beyond the scope of the present study. Experimental data, however, offer some possible explanations: while the immediate effects on pain and knee flexibility exclude structural changes in the affected joints as the underlying mechanism of acupuncture in this experimental setting, they do, however, indicate an underlying neural mechanism [36
]. It remains speculative as to whether this reflex-like effect involves functional changes within higher regions of the central nervous system or whether regional effects on musculoskeletal dynamics and connective tissue structures may be the dominant mechanism. The observed immediate effects, however, make a primarily systemic or humoral effect rather unlikely. As the systematic search for acupuncture points with altered perception is an integral part of history taking and work-up for the Chinese diagnosis, it is conceivable that the individualised diagnostic approach may enhance the chance to effectively identify needling points with the potential for reducing functional limitations. The present study suggests that the methodology of arriving at acupuncture points may matter. In the present study, classical acupuncture outperformed modern acupuncture. Future acupuncture studies should, therefore, consider potential differences arising from the modality of acupuncture techniques in the study design.
Several caveats of the present investigation require consideration. Firstly, we studied each acupuncture technique only once in each patient, and treatments were usually one week apart. Thus, we are unable to infer the long-term or cumulative effects of repeated applications; the study should, therefore, be considered a proof of concept study.
The available data from the present study corroborate a rapid decline, particularly of the non-specific pain relief effect, within one week. Secondly, the present data suggest that effects on knee mobility are somewhat retained. However, the imperfect retest reliability of repeated knee-flexion measures after one week suggests viewing this result with caution and encourages repetition in other studies. Thirdly, crossover designs are prone to carry-over effects. We cannot rule out residual carry-over effects beyond those explicitly modelled within the multilevel statistical method. Finally, while the data support the notion that the choice of needling points matters, the relevant aspects of the Chinese diagnosis still remain to be elucidated. This, however, cannot be addressed in this work.