Complementary & Alternative Therapies For Arthritis
by Joan Bathon, M.D. and Andrew Bilderback
Introduction
Interest in complementary and alternative medicine (CAM) in general has exploded in recent years. A recent survey of patients in rheumatological practicesref 1 indicated that over half of patients were using various CAM modalities and 90% have used them in the past. Multivariate analyses demonstrated that persons that used CAM regularly were more likely to have osteoarthritis and severe pain. Arthritis is a common problem and a chronic disabling condition. For many patients conventional therapies are not effective and are limited by side effects. This leads to ongoing pain and frustration and hence toward seeking alternative therapies. CAM therapies are defined as being outside scientific mainstream medicine. These non-pharmaceutical treatments are generally unproven in efficacy but perceived as safe. The American College of Rheumatology (ACR) believes practitioners should be informed about CAM therapies and be able to discuss them knowledgably with patients. Meanwhile scientific studies are underway to test the efficacy of these modalities.
Although a broad spectrum of treatment modalities is found under the umbrella of CAM, this discussion will be limited to the therapies listed below. It is imperative that practitioners familiarize themselves with these treatment methods to help guide their patients.
Acupunture Manipulation
Acupuncture has become one of the most popular unconventional therapies within the United States. It is gaining acceptance, and is even covered by some insurers and managed health organizations. The World Health Organization (WHO) recommends it for chronic pain and the Food and Drug Administration (FDA) regulates acupuncture needles as medical devices. The general theory of acupuncture is based on the premise in Chinese medicine, that there are patterns of energy flow (meridians) in the body that are essential to health. Acupuncture is believed to correct imbalances in this energy flow, by targeting acupuncture points distributed along the meridians. Although puncturing the skin with thin long needles is the standard approach, there are many variations including the use of heat, pressure, friction, suction, or electrical stimulation.
Osteoarthritis (OA)
A number of controlled trials have been conducted during the past several decades suggesting that acupuncture is effective for the pain associated with osteoarthritis. Although multiple studies have suggested the effectiveness of acupuncture for osteoarthritis, these studies have lacked sufficient power to detect a significant difference between placebo and acupuncture treated groups. Berman et alref 2 recently completed a pilot study and a follow up of a larger, single blind randomized trial on the effect of acupuncture on OA of the knee in an elderly population. Patients in the pilot study (N=12) showed significant improvement in pain scores and self-reported function, and in performance measures of function after 8 weeks of acupuncture treatment. Scores of the outcome measures at 12 weeks showed improvement over baseline scores. In the larger (N=58) follow up trial, which examined the effect of acupuncture added to NSAID oral medication management, the acupuncture treated group had significant improvement in self reported pain and disability scores compared with controls.
Rheumatoid Arthritis (RA)
There have been a number of studies in the literature reporting that acupuncture is effective in treating rheumatoid arthritis. Only one of these was a true randomized controlled trial, however. This study used 10 patients with symmetric joint involvement and treated one knee with sham acupuncture and one knee with real acupuncture. The investigators reported that there was a significant improvement in pain relief in the knee treated with real acupuncture compared with the knee treated with sham acupuncture. Perhaps the most important finding of this study is that the average pain-free duration in the acupuncture-treated knee was 1 to 3 months versus less than 10 hours in the sham acupuncture-treated knew. This is a small group of patients and more studies assessing the effectiveness of acupuncture for rheumatoid arthritis are warranted.
Summary
Although there is not yet definitive evidence from a large scale randomized controlled trial (RCT) that acupuncture is effective for treating rheumatological conditions, there is moderately strong evidence from the above studies to support the use of acupuncture as an adjunctive therapy for osteoarthritis. On the other hand, the only RCT of acupuncture for rheumatoid arthritis employed too small a sample size for any statistically significant result to emerge. Physicians should be willing to discuss with their patients the potential use of acupuncture as a means of pain management. Also the NIH consensus panel on acupuncture stated that the occurrence of adverse events during needle manipulation has been documented to be extremely low.
Dietary Supplementation
Glucosamine
Glucosamine has been studied as a therapeutic agent for decades, but only recently has become popular for treating osteoarthritis. This is in part due to the 1994 Dietary Supplement and Health Education Act and the reaction to the book The Arthritis Cure. Glucosamine is an aminomonosaccharide found in articular cartilage. In vitro studies using human chondrocytes showed that glucosamine also stimulated proteoglycan synthesisref 3. This potential mechanism is attractive as treatment for osteoarthritis because in OA proteoglycan production does not keep pace with its loss, resulting in a net loss of cartilage matrix. High doses of oral glucosamine administered to rats had a mild anti-inflammatory effect in adjuvant-induced arthritis.
Reicheltref 4) reported a large multicentric, randomized, double blind, placebo-controlled trial of glucosamine sulfate in osteoarthritis of the knee in 1994. Diagnosis was made based on the clinical and radiological criteria of Lequesne. All patients were symptomatic with pain at rest or on movement and had functional limitations. One hundred fifty-five patients were randomized to receive either 400 mg of glucosamine sulfate or placebo intramuscularly twice weekly for 6 weeks. Assessment occurred on days 3 and 7 each week during the study period and at 2 weeks following the conclusion of the study. A positive response to drug therapy was defined as a decrease in the Lequesne index of 3 points and the investigator's judgment of good or moderate effects. All patients in the study were symptomatic for at least 6 months prior to the study. Nonsteroidal anti-inflammatory drugs, corticosteroids, or other arthritis therapies were not allowed to be used by the subjects, except for acetaminophen as a rescue medication. Subjects needing acetaminophen for pain control were automatically classified as non-responders. Seventy-nine subjects were placed in the glucosamine group and 76 in the placebo group. There were 6 and 7 dropouts, respectively, but they were included in the intent to treat analysis.
Two subjects receiving glucosamine and six receiving placebo-required acetaminophen and were considered to be nonresponers. Fifty-five percent of the glucosamine group was responders compared with 33 % of the group-receiving placebo, which is a statistically significant difference. Intent to treat analysis resulted in similar findings. The subjects receiving active therapy had significantly better improvement in the Lequesne index at 5 and 6 weeks than the placebo group, and the improvement was sustained at the 2- week post-treatment assessment. In both groups, there was a progressive improvement in symptom scores during the 6-week trial. This particular study was well designed. Unfortunately, an intramuscular formulation was used and extrapolation of the results and may not be valid.
A double-blind trial in 178 Chinese patients with osteoarthritis of the knee was reported by Qiu in 1994ref 5. Eighty-eight subjects were randomized to receive 500 mg of glucosamine sulfate and one ibuprofen placebo capsule tree times daily, and the other 90 subjects received 400 mg of ibuprofen and glucosamine placebo capsules three times daily. The duration of therapy was 4 weeks, followed by a 2-week drug-free interval. Pain scores were assessed for tenderness and for pain at rest and during movement using a 0 to 3 scale. Knee swelling was also assessed using a 0 to 3 scale. Physician evaluation of improvement was rated as worsened, unchanged, improved, or definitely improved (almost completely free of symptoms). No diagnostic criteria for osteoarthritis were given.
Both groups showed statistically significant improvement in composite pain scores at 2 and 4 weeks of therapy. Decrease in pain scores progressed throughout the study period and were sustained after a 2-week washout period at week 4. Glucosamine decreased pain scores by 57% and ibuprofen lowered these scores by 51%. Overall, the physician rating at 4 weeks identified 45% of subjects as symptom-free and 39% as improved in the glucosamine group, compared to 32% of subjects symptom-free and 45% as improved in the ibuprofen group. At the end of the 2-week wash-out period, however, the glucosamine group had a significantly better improvement rating than did the ibuprofen group, with 55% of the glucosamine-treated subjects being symptom-free compared with 36% in the ibuprofen group.
Reginster et alref 6 conducted a randomized, double-blind placebo controlled trial examining the effects of glucosamine on the long-term progression of osteoarthritis. Two-hundred twelve patients with knee osteoarthritis were randomized to receive either 1500 mg glucosamine sulfate or placebo once-a-day for three years.
Radiographs of each knee were taken at enrollment and after one and three years. The patients on placebo had a mean joint-space loss of -.31 mm. Patients who had received glucosamine sulfate had a mean joint-space loss of -.06 mm, a statistically significant finding. This indicates glucosamine sulfate may be able to slow the natural progression of osteoarthritis of the knee. Of note, there were no differences in safety or early withdrawal between the placebo and treatment groups.
All of the published reports on clinical trials of glucosamine in OA have resulted in favorable outcomes. Unfortunately, many of these studies have significant flaws in experimental design. Nevertheless, the data from a few quality studies discussed above are suggestive that glucosamine is effective in the control of pain symptoms and is potentially a disease-modifying agent in the treatment of knee OA. When taken orally, it is safe but there are few long-term data. Glucosamine may thus be effective in decreasing the symptoms of OA; however it should be recommended to patients with the attitude that additional long-term efficacy studies need to be performed.
Chondroitin Sulfate
Frequently sold in combination with glucosamine, chondroitin sulfate is a proteoglycan and a major component of articular cartilage. It is hypothesized to work by increasing levels of chondroitin sulfate in the blood and subsequent incorporation into the cartilage. Additionally, in vitro studies have demonstrated that chondroitin sulfate can stimulate production of other important cartilage proteoglycans.ref 4 & 7 A number of clinical studies have now demonstrated that chondroitin sulfate therapy does indeed produce clinical benefits.
Bourgeois et alref 8 conducted a multicenter, randomized, double-blind, controlled study which compared 1200 mg/day chondroitin sulfate to placebo. One hundred twenty-seven patients were randomized to receive either placebo, chondroitin sulfate 1200 mg/day, or chondroitin sulfate 3x400 mg/day. In the chondroitin sulfate groups, the Lequesne’s Index, and the patient and physician overall assessments were significantly improved compared to baseline (P<0.01 for both assessments). In contrast, there was only a slight improvement observed in the placebo group. Both the physician’s and patient’s overall efficacy assessments were significantly better in the chondroitin sulfate group than in the placebo group (P<0.01). Of note, there was no difference in efficacy between the single dose of 1200mg chondroitin sulfate and the 3x400mg daily doses of chondroitin sulfate for any of the clinical parameters studied.
Morreale, et alref 9 conducted a randomized, multicenter, double blind, double dummy study comparing the efficacy of chondroitin sulfate with diclofenac sodium, a commonly used anti-inflammatory drug. One hundred forty-six patients with OA of the knee were randomized to receive either chondroitin sulfate or diclofenac sodium for six months. Patients who had received diclofenac sodium had a quick decrease in pain symptoms which, however, reappeared after the end of treatment. A clinical reduction in symptoms was observed later in time in patients who had received chondroitin sulfate, but the symptoms did not reappear for up to 3 months after the end of treatment.
A recent metaanalysisref 10 of seven studies including the two discussed above concluded that chondroitin sulfate may be useful in decreasing pain and improving function in osteoarthritis. Pooled data showed at least a 50% improvement in VAS pain scores and the Lequesne functional index. The pool consisted of 372 patients with OA of the hip or knee who had received chondroitin sulfate and 331 who had received placebo. Patients were followed 120 or more days. In all of the studies, chondroitin sulfate was safe and there was no higher incidence of adverse events when compared to placebo. However, the metaanalysis was only comprised of seven studies, each of which examined a small number of patients. Thus, it is not possible to conclude anything more than that chondroitin sulfate may be useful in the treatment of osteoarthritis. Larger studies are needed to further examine the usefulness of chondroitin sulfate in osteoarthritis. No long-term studies examining the effect of chondroitin sulfate on radiographic progression are available.
Magnetic Therapy
A foundation of in vitro and clinical studies has demonstrated that electric and magnetic energy favorably affects disorders of dense connective tissue. These signals have become a fertile area of research in orthopedics and rheumatology. Surprisingly modern pulsed electromagnetic fields (PEMF) have been available for over 20 years, although only now are they becoming a standard of care for delayed union fracture. Bassett et alref 11 published some interesting results showing PEMF therapy healed a nonunion fracture in four months. This fracture had previously failed several operations over a 10-year interval and the alternative treatment being offered was amputation of the limb. This finding inspired much research that culminated in the development of bone growth stimulators that were approved by US FDA IN 1979. Currently it is well known that PEMF stimulation has become an effective alternative therapy to orthopedic surgery, with success rates as high as 80%. In 1990 Lippiello et alref 12 showed that PEMF application, stimulated chondrocytic proliferation in 37 New Zealand white rabbits.
Electromagnetic fields can be delivered to biological systems by using direct placement of an electrode or noninvasively by capacitive coupling (opposing electrodes placed on skin across the target area) or inductive coupling (PEMF induce an electric current in the target area without skin contact altogether).
In a randomized trial, Zizic et alref 13 studied a pulsed electric device used to treat 78 patients with chronic knee osteoarthritis via skin surface electrodes. The active treatment was superior to placebo in symptom reduction and was proved to be effective for symptom reduction and cost effective. The application of PEMF stimulation for osteoarthritis is a relatively new area, which has been supported by additional work by Trock et al inref 14 1994. In their experiment 86 patients with knee osteoarthritis were exposed to 9 hours of PEMF stimulation over a 1-month period using a noncontact device. Up to 36% of the patients noticed improvement in pain and function. Perrot et al reported similar finding in his 1998 experiment. PEMF therapy is considered safe but should be avoided in those who are pregnant, with permanent pacemakers and patients with known cancer. Due to their safety, cost effectiveness coupled with their proven effectiveness as a treatment tool for delayed fractures, interest is directed towards osteoarthrits, osteonecrosis and osteoporosis by way of large independent studies currently in progress.
References
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