By Yoon-Hang Kim, MD, MPH, DABMA, Consulting Physician at the Institute for Health and Healing, California Pacific Medical Center, in San Francisco.
Osteoarthritis is the most common joint disorder in the world. Radiographic evidence of knee osteoarthritis (OA) is found in the majority of people by age 65 and in about 80% of those age 75 and older.1 Approximately 11% of persons age 64 and older have symptomatic OA of the knee.2 In addition to decreased mobility due to pain and emotional suffering, patients with knee OA are at an increased risk for falls.3 With the continued growth of the elderly population in the United States, OA is becoming a major medical and financial concern.
Conventional medical approaches to treating knee OA range from conservative management with nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy modalities to invasive interventions such as steroid injection, arthroscopic procedures, and knee replacement surgery. The safety of NSAIDs has been questioned on many levels. Acute renal failure secondary to NSAID use is well documented. Stiefelhagen reported a case of a patient with acute renal failure caused by NSAIDs and concluded that successful treatment of knee pain had been achieved, but the patient had died.4
Bjordal et al conducted a meta-analysis on the efficacy of NSAID medications for osteoarthritic knee pain and concluded that NSAIDs can reduce short-term pain in OA of the knee slightly better than placebo, but long-term use of NSAIDs for this condition should be avoided.5 As serious adverse effects are associated with oral NSAIDs, only limited short-term use can be recommended.
In 2001, Hochberg called for the re-evaluation of NSAIDs as the first-line OA agent, urging clinicians instead to consider glucosamine sulphate, and expressed hope for the role of COX-2 inhibitors.6 However, in 2004, the FDA issued a Public Health Advisory recommending limited use of COX-2 inhibitors in light of the possible associated increased cardiovascular risk.7
Acupuncture is one of the most popular forms of complementary and alternative medicine and is rapidly gaining acceptance in the United States. In 1997, the National Institutes of Health (NIH) Consensus Panel concluded that acupuncture is effective for adult postoperative and chemotherapy-related nausea and vomiting and probably for the nausea of pregnancy.8 Furthermore, the panel concluded that there are reasonable studies showing relief with acupuncture on such diverse pain conditions as menstrual cramps, tennis elbow, and fibromyalgia. Since then, a number of well-designed, high-quality randomized, controlled trials clarified the efficacy of acupuncture for treating many entities including cocaine dependence, back pain, and osteoarthritic knee pain.
Mechanism of Action
Since the late 1970s, acupuncture analgesia has been demonstrated to activate the endogenous opioid peptide system and influence the body’s pain regulatory mechanism by changing the processing and perception of noxious information at various levels of the central nervous system.7
It is widely believed that acupuncture analgesia is initiated by stimulation of small diameter nerves in muscles, which send impulses to the spinal cord, midbrain, and pituitary gland, resulting in the release of neurotransmitters such as monoamines and endorphins, which in turn block pain signal transduction.9
Two model systems of acupuncture analgesia have been proposed:
Endorphin-dependent system: The discovery of naloxone, an endorphin antagonist, helped elucidate the role of endorphins in acupuncture. Naloxone was shown to block acupuncture analgesia in human volunteers in a randomized, double-blind study.10 A subsequent study produced the same results, fashioned a dose-response curve for naloxone, and found that increasing doses created increasing blockade.11 The endorphin-dependent system can be activated through low-frequency, high-intensity electrical stimulation of acupuncture needles. The pain relief is characterized by a slow onset throughout the body and cumulative effect upon subsequent stimulation.9
Monoamine-dependent system: In addition to endorphins, monoamines such as serotonin and norepinephrine have been shown to be involved in acupuncture analgesia. Microinjections of serotonin antagonists and norepinephrine antagonists have blocked the effect of acupuncture analgesia.12,13 The monoamine-dependent system can be activated through high-frequency, low-intensity electrical stimulation of acupuncture needles. Pain relief is rapid in onset and segmental, and offers no cumulative effect upon subsequent stimulation.9
Systematic Review
Ezzo et al published a systematic review of seven randomized controlled trials (RCTs) and concluded that strong evidence exists that acupuncture is more effective than sham acupuncture for pain relief but not for functional improvement.14 Three studies with sham acupuncture as a control were reviewed; two studies found more significant improvements in pain with acupuncture compared to sham, while the third did not. Ezzo et al noted that in the two studies that showed benefit, the sham acupuncture consisted of needles placed at distal non-acupuncture points, which they refer to as "minimal sham." In the third study, which did not show a benefit for sham acupuncture, the sham acupuncture was at sites one inch adjacent to the real points, which the authors note may have inadvertently elicited an analgesic response.
Clinical Trials
In 2001, Singh et al conducted an RCT with 73 patients with symptomatic OA of the knee.15 Patients self-scored on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Lequesne Algofunctional Index at baseline and at weeks 4, 8, and 12. Results demonstrate that patients’ scores on both indices improved at weeks 4, 8, and 12. Scores were stable regardless of the baseline severity of the OA. However, the group with the least disability and pain rebounded to original levels to a greater degree than did those who initially were more hindered by the condition. The more disabled groups retained the benefits of acupuncture treatment through the 12-week period. Singh et al concluded that acupuncture for patients with OA of the knee may best be used early in the treatment plan, with a decrease in treatment frequency once the acute treatment period is completed to avoid a rebound effect.
Tillu examined the effects of acupuncture on patients with advanced OA of the knee awaiting total knee joint replacement.16 Forty-four patients were randomly assigned to two groups. The first group received acupuncture to the most affected knee only and the other group received acupuncture to both knees. A blinded observer assessed knee function before starting treatment, and at months 2 and 6. Analysis showed a significant reduction in symptoms in both groups, and this improvement was sustained for six months. However, there was no statistically significant difference between the groups. The author concluded that unilateral acupuncture is as effective as bilateral acupuncture in increasing function and reducing the pain associated with OA of the knee. However, this research design did not control for nonspecific effects of needling.
In 2003, Ng et al performed an RCT of the effectiveness of electro-acupuncture (EA) vs. transcutaneous electrical nerve stimulation (TENS) in alleviating OA-induced knee pain.17 Twenty-four subjects were assigned to EA, TENS, or a control education group. After eight sessions of treatment, there was significant reduction of knee pain in the EA and TENS groups compared to the control group. The results obtained by Ng et al are consistent with the conclusion of a Cochrane Database System Review prepared by Osiri et al,18 in which TENS and EA were shown to be more effective in pain control than placebo.
In 2004, four trials were conducted investigating the effectiveness of acupuncture for treating OA of the knee. Tukmachi et al conducted an RCT in which subjects were assigned to one of three groups.19 The first group received acupuncture alone, the second group received acupuncture plus medication, and the third group used medication for the first five weeks and then added a course of acupuncture to the medication. Repeated measure analyses revealed a highly significant improvement in pain (VAS) after the courses of acupuncture in patients receiving acupuncture alone (P = 0.012) and patients receiving medication and acupuncture (P = 0.001) vs. the wait-list control group. There was no change in the control group until after the course of acupuncture was added to the medication; the improvement was significant (P = 0.001). These benefits were maintained for one month after the course of acupuncture. The authors concluded that manual acupuncture and EA cause a significant improvement in the symptoms of OA of the knee, either on their own or as adjunct therapy, with no loss of benefit after one month.
Vas et al completed two studies in 2004. The first was a large case series consisting of 563 patients treated with acupuncture as an adjunctive treatment for OA.20 Their results showed that 75% of the patients achieved a reduction in pain of 45% or more with the addition of acupuncture. In the second study, an RCT, 97 patients were randomly assigned to two groups, the first group receiving acupuncture plus diclofenac (n = 48) and the second receiving placebo acupuncture plus diclofenac (n = 49).21 Patients in the intervention group experienced a greater reduction in pain than did the control group (mean difference 23.9; 95% confidence interval [CI] 15.0-32.8) using the WOMAC scale. The same result was observed in the pain visual analog scale, with a reduction of 26.6 (95% CI 18.5-34.8). Vas et al concluded that acupuncture plus diclofenac is more effective than placebo acupuncture plus diclofenac for the symptomatic treatment of OA of the knee.
Perhaps the most significant study assessing the effect of acupuncture to treat OA of the knee was conducted by Berman et al in 2004.22 The study was the largest randomized, controlled phase III clinical trial of acupuncture ever conducted. Five hundred seventy patients with OA of the knee were divided into two groups: a true acupuncture group and a sham acupuncture group. Primary outcomes were changes in pain and function scores (assessed using WOMAC) at weeks 8 and 26. Participants in the true acupuncture group experienced greater improvement in WOMAC function scores than the sham acupuncture group at week 8, but not in WOMAC pain score. However, at week 26, the true acupuncture group not only experienced significantly greater improvement than the sham group in the WOMAC function score, but also in WOMAC pain score and patient global assessment. The authors concluded that acupuncture provided improvement in function and pain relief as an adjunctive therapy for OA of the knee when compared with credible sham acupuncture and control education groups. This trial seems to infer that acupuncture treatment may need to continue longer than eight weeks.
The impact of Berman’s study is best described by Stephen E. Straus, MD, Director, National Center for Complementary and Alternative Medicine, NIH:23
"For the first time, a clinical trial with sufficient rigor, size, and duration has shown that acupuncture reduces the pain and functional impairment of osteoarthritis of the knee. These results also indicate that acupuncture can serve as an effective addition to a standard regimen of care and improve quality of life for knee osteoarthritis sufferers."
In 2003, Centers for Medicare and Medicaid Services (CMS) commissioned a Technology Assessment to review evidence regarding the use of acupuncture for OA. The results of Berman et al lend support to the decision to provide greater access to acupuncture and to include acupuncture as a covered benefit through CMS.
Adverse Effects/Safety Trials
The safety of acupuncture is well documented. Ernst and White conducted a systematic review to determine the incidence of adverse events associated with acupuncture.24 The most common adverse events were needle pain, tiredness, and bleeding. Feelings of faintness and syncope were uncommon. Pneumothorax was rare, occurring only twice in nearly a quarter of a million treatments. However, the use of non-sterile needles may cause infections. One overview identified 126 documented cases of hepatitis associated with acupuncture.25
Conclusion
A significant amount of data exists supporting the effectiveness of acupuncture for treating OA of the knee. The recently completed phase III trial strongly supports the role of acupuncture for treating knee OA.
Recommendation
Knee OA is a prevalent medical problem with huge social, economic, and medical implications. Given the risk of currently available medical therapy, physicians may choose to employ a trial of acupuncture for their patients with OA, especially for those most at risk for adverse drug events associated with NSAID use.
References
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