Although there are several lines of evidence from many controlled and uncontrolled studies for the short-term and long-term effectiveness of acupuncture in relieving clinical pain [23
], the scientific data concerning the efficacy of acupuncture in OA are rare [19
]. In addition, there are several systemic flaws [29
] among these studies due to inadequate statistical power, inadequate sessions of acupuncture treatment, failure to control concomitant therapies, or no sham/placebo acupuncture controlled group. In this study, we minimized the methodological limitations of previous studies by using the randomized, single-blind, placebo controlled design with a larger sample size of OA patients coupled with standard outcome assessments. By using the percentage of the responders as the main efficacy criterion, the comparison between true and sham acupuncture needs at least 61 patients per group, whereas, only 35 patients per group are needed to compare between true and placebo acupuncture performed by not puncturing the skin [23
]. In order to increase the ability of differentiating true from placebo effects and minimize the sample size, we selected the procedure of attaching the acupuncture points with the patch electrodes as placebo EA, and at least 45 completers per group were treated in this trial. In this study, a double-blind design was considered inappropriate, since we used patch electrodes as placebo EA and our patients might have recognized the difference between true and placebo EA. A single blind was, therefore, a reasonable alternative.
The acupuncture points used were selected because we intended to determine only the effects of local points around the affected knee. This applied especially to the medial aspect, which related to the knee compartment that was frequently involved in OA. Using these local points coupled with the needling technique (developed by Chawal Kanchanakul, acupuncturist of Dhammanamai Foundation, Chiang Mai, Thailand) demonstrated a rather simple, convenient, less painful, and more acceptable method for Thai patients, and it was effective in our pilot study. The points selected here were therefore different from other trials [24
], which also included the distal points at medial and lateral aspects of the leg. Low-frequency (2 Hz) EA was selected because it produces an analgesia of long duration, which outlasts the 20-min stimulation session by 30 min to many hours. In addition, its effects are cumulative after several sessions of treatment given either daily or less frequently (2–3 times a week) [30
]. For these reasons, the low-frequency EA in this study was therefore given 3 times a week for 4 weeks, as commonly recommended in EA practice. However, to balance the acupuncture point stimulation by positive and negative polarities, each point was stimulated 6 times with positive and negative polarities in an alternate sequence during 12 sessions of treatment. In addition, each pair of electrodes was connected to each pair of adjacent points in order to obtain equal electrical sensation in each point during stimulation.
In this study, the clinical responses observed in the placebo group might result from, 1) the placebo effect or natural fluctuations in the symptoms of OA that are unrelated to the analgesic effect of paracetamol, because some patients demonstrated reductions in these scores without or with minimal analgesic need, or 2) the direct effects of paracetamol as a rescue analgesic. The latter reason made the placebo group not absolutely inert because paracetamol is also the first-line drug in the treatment of OA of the knee. However, the use of a rescue analgesic could not be avoided due to ethical reasons.
At week 4, the improvement of symptom scores (except change in WOMAC pain index and WOMAC total score) and the number of responders/patients with the opinion of "much better" were greatest in the EA group. These data indicate the great potential of EA in the symptomatic treatment of OA of the knee. This study also demonstrated that EA was significantly more effective than placebo with respect to changes in VAS and Lequesne's functional index, and significantly more effective than diclofenac with respect to the changes in VAS. This superiority of EA indicates its genuine efficacy [17
], which was more effective than placebo (or diclofenac) in this study. A previous trial revealed 34% and 14% reductions in the mean values of WOMAC total score and Lequesne's index, respectively after 4 weeks of acupuncture treatment [28
], whereas, our study demonstrated a 50% and 45% reduction, respectively. These discrepancies might be due to differences in acupuncture point selection, number of points and the electrical stimulation technique used, or electrical stimulation parameters.
The clinical responses in the combined group were slightly superior to the diclofenac group, but not to the EA group (except for the tendency of being superior with respect to a change in the subscale of the standardized WOMAC: pain index). These responses indicate that EA may exert an adequate analgesic effect, a combination with diclofenac may not be of further benefit. Although a combination was not more efficacious than EA alone, it was significantly more so compared to placebo in terms of improvement in the WOMAC pain index, while EA was not. However, the nonsignificant change in clinical scores between the diclofenac and placebo group indirectly suggests that diclofenac may be as effective as paracetamol (as needed) in symptomatic treatment of OA of the knee.
The nonsignificant change in paracetamol consumption among the four groups during treatment might result from the unnecessary use of paracetamol in a great majority of active treatment groups, despite a significant improvement in some parameters of the EA and combined group, and a tendency to improve parameters in the diclofenac group. Another possibility might be the large variation in paracetamol consumption in each group that contributed to a false negative result. The nonsignificant change in the 50 feet-walk time among the four groups suggests that this parameter may not be sensitive enough to demonstrate existing differences. Walk time determined during stair climbing should thus be a better alternative [31
]. The failure to demonstrate the differences in other parameters (i.e. change in WOMAC stiffness, disability, and total scores) between the active treatment and placebo group may be due mainly to the rescue analgesic and partly to inadequacy of the sample size.
This study demonstrated that EA treatment was safe and free from serious adverse effects. However, the indifference in adverse events between the diclofenac and placebo group might be due to the exclusion of patients who were at high risk to the adverse effects of NSAIDs during the screening visit or short-term trial. In this study, the rescue analgesic paracetamol contributed to several confounding effects. Therefore, the randomized placebo controlled trial without using rescue analgesic should be investigated further to confirm the effectiveness of this range of active treatment, especially in EA and its combination with NSAIDs.
In summary, EA was significantly more effective than placebo regarding reductions in 100 mm VAS and Lequesne's functional index, but was significantly more effective than diclofenac in only the reduction of 100 mm VAS. The combination of EA and diclofenac treatment was more effective than placebo with respect to the reduction in the subscale of standardized WOMAC (pain index), but not more effective than EA treatment alone. Local contusions were minor adverse effects commonly found in the EA and combined group. The positive effects far outweigh the serious adverse ones of EA, which make this procedure an attractive alternative treatment for patients with OA of the knee.