Effectiveness of Acupuncture as Adjunctive Therapy in Osteoarthritis of the Knee

Context Previous studies of acupuncture for osteoarthritis have had conflicting results. This may have occurred because most studies have included small samples, a limited number of treatment sessions, or other limitations. Contribution This randomized, controlled trial compared 24 acupuncture sessions over 26 weeks with sham acupuncture or arthritis education in 570 patients with osteoarthritis of the knee. Acupuncture led to greater improvements in function but not pain after 8 weeks and in both pain and function after 26 weeks. No adverse effects were associated with acupuncture. Cautions Many participants dropped out of the study, so readers should interpret the findings at 26 weeks with caution. The Editors Osteoarthritis is the most common form of arthritis and is a major cause of morbidity, limitation of activity, and health care utilization, especially in elderly patients (1, 2). Pain and functional limitation are the primary clinical manifestations of osteoarthritis of the knee. Current recommendations for managing osteoarthritis, including guidelines published by the American College of Rheumatology (3) and European League of Associations of Rheumatology (4), focus on relieving pain and stiffness and maintaining or improving physical function as important goals of therapy. No curative therapies exist for osteoarthritis; thus, both pharmacologic and nonpharmacologic management focus on controlling pain and reducing functional limitation (5). Nonpharmacologic therapy, which includes patient education, social support, physical and occupational therapy, aerobic and resistive exercises, and weight loss, is the cornerstone of a multidisciplinary approach to osteoarthritis patient management (3). Pharmacologic therapies include nonopioid analgesics (such as acetaminophen), nonsteroidal anti-inflammatory drugs (NSAIDs) (including cyclooxygenase-2 [COX-2] enzyme selective inhibitors), topical analgesics (capsaicin cream), opioid analgesics, and intra-articular steroid and hyaluronate injections. Often, these agents are used in combination for additive analgesic efficacy (6). Pharmacologic management of osteoarthritis is often ineffective, and agents such as NSAIDs may cause unwanted and dangerous side effects (7, 8). Complementary and alternative medicine is another approach to treating osteoarthritis (9-12), particularly in Asian societies (13). Many U.S. patients with osteoarthritis also use complementary and alternative medical therapies (14). A systematic review of acupuncture and knee osteoarthritis (15) identified 7 small randomized, controlled trials published in English. Within the methodologic limitations of the studies, the evidence suggested that acupuncture seemed to alleviate knee pain and function compared with sham acupuncture controls, although 2 trials comparing acupuncture with an active, nonpharmacologic treatment (physical therapy) did not indicate such an effect (16, 17). Before conducting our large-scale trial, we completed both a pilot study (18) and a randomized, single-blind trial (19) of the effect of acupuncture on osteoarthritis of the knee. Participants in the uncontrolled pilot study (n= 12) showed statistically significant improvement in both self-reported pain and physical function, as well as performance measures of physical function after 8 weeks of acupuncture treatment and at 12-week follow-up as compared with their baseline (18). In our larger randomized, single-blind trial (n= 73), which examined the benefit of acupuncture added to standard management with NSAIDs, the acupuncture treatment group experienced statistically significant improvements in self-reported pain and disability scores compared with a standard-care control group as late as 4 weeks after the end of treatment (19). However, this effect diminished within 18 weeks (26 weeks after the beginning of the trial) after the final acupuncture treatment. Together, however, the previously conducted trials (both our preliminary studies [18, 19] and those referenced in the systematic review [15]) have 3 methodologic limitations: lack of credible controls for the placebo effect, inadequate assessment of long-term treatment benefits, and insufficient sample sizes. We tested the hypothesis that an 8-week intensive acupuncture treatment regimen, followed by an 18-week tapering regimen, reduces pain and improves function among patients with knee osteoarthritis as compared with both sham acupuncture and education control groups. Methods Patient Recruitment We recruited patients for this multisite, placebo-controlled trial from March 2000 through December 2003, primarily through print and radio advertisements. The 3 sites were the Integrative Medicine Clinic of the University of Maryland School of Medicine, Baltimore, Maryland; the Innovative Medical Research Center (a private research firm), Towson, Maryland; and the Hospital for Special Surgery, New York City, New York. The institutional review boards of the 3 sites approved the study. We determined the sample size (n= 570) by a power analysis based on our randomized pilot study (19), adjusted by the estimated decrease in effect size resulting from the inclusion of a sham acupuncture group designed to control for placebo effects. Patients met the following inclusion criteria: age 50 years or older, a diagnosis of osteoarthritis of the knee, radiographic evidence of at least 1 osteophyte at the tibiofemoral joint (KellgrenLawrence grade 2), moderate or greater clinically significant knee pain on most days during the past month, and willingness to be randomly assigned. Exclusion criteria were the presence of serious medical conditions that precluded participation in study, bleeding disorders that might contraindicate acupuncture, intra-articular corticosteroid or hyaluronate injections (as well as any knee surgeries or concomitant use of topical capsaicin cream) during the past 6 months, previous experience with acupuncture, or any planned events (including total knee replacement) that would interfere with participation in the study during the following 26 weeks. After a brief telephone screening, patients were scheduled to visit 1 of the 3 participating sites to sign an informed consent statement and undergo a brief rheumatologic examination (including radiographic examination of affected knees) by a physician or a nurse practitioner. Because the education course was a group activity, patients were recruited until a cohort of 12 to 21 patients was formed, at which point each cohort at each site was randomly assigned to 1 of 3 groups by a computer-generated process using randomly selected blocks of 3, 6, and 9. We assured allocation concealment by using disguised letter codes that were generated and sent to the site coordinators by a central statistical core. We used this procedure to ensure that approximately equal numbers of participants were in each treatment group across the course of the study, to ensure that each cohort would have participants assigned to all 3 treatment groups, and to make the breaking of the group assignment process more difficult. The research assistants who collected assessments from participants, the participants themselves (in the true acupuncture and sham acupuncture groups), and the statistician were blinded to group assignment. Assessments were conducted at baseline and 4, 8, 14, and 26 weeks after randomization. Study Interventions We developed and modified the acupuncture treatment and sham control protocols from previously reported and validated procedures (18-21). During the trial, 7 acupuncturists were used: 3 at the Integrative Medicine Clinic, 3 at the Innovative Medical Research Center, and 1 at the Hospital for Special Surgery. In general, acupuncturists were assigned to the same participants throughout the 26-week treatment schedule, except for vacation conflicts and staff turnover, and provided approximately the same proportions of true versus sham procedures. All acupuncturists were state-licensed and had at least 2 years of clinical experience. The study's principal acupuncturist trained and supervised the acupuncturists in performing true or sham procedures and avoiding interactions that could inadvertently communicate group assignment. True Acupuncture The true acupuncture (experimental) group underwent 26 weeks of gradually tapering treatment according to the following schedule: 8 weeks of 2 treatments per week followed by 2 weeks of 1 treatment per week, 4 weeks of 1 treatment every other week, and 12 weeks of 1 treatment per month. We based the acupuncture point selections on Traditional Chinese Medicine meridian theory to treat knee joint pain, known as the Bi syndrome. These points consisted of 5 local points (Yanglinquan [gall bladder meridian point 34], Yinlinquan [spleen meridian point 9], Zhusanli [stomach meridian point 36], Dubi [stomach meridian point 35], and extra point Xiyan) and 4 distal points (Kunlun [urinarybladder, meridian point 60], Xuanzhong [gall bladder meridian point 39], Sanyinjiao [spleen meridian point 6], and Taixi [kidney meridian point 3]) on meridians that traverse the area of pain (22, 23). The same points were treated for each affected leg. If both knees were affected, 9 needles were inserted in each leg. (The outcome measures were not specifically targeted to whether the patient had osteoarthritis in 1 or both knees, and we observed no differential effects on the basis of the number of knees treated.) The acupuncturists inserted 1.5-inch (for local points) and 1-inch (for distal points) 32-gauge (0.25-mm diameter) acupuncture needles to a conventional depth of approximately 0.3 to 1.0 inch, depending on point location. All participants in the treatment group achieved the De-Qi sensation, a local sensation of heaviness, numbness, soreness, or paresthesia that accompanies the insertion and manipulation of needles during acupuncture, at these 9 points. Acupuncturists applied electrical stimulati