Osteoarthritis (OA) is characterized by degradation of both proteoglycans within the cartilage and subchondral bone in the joint. Continued breakdown of proteoglycans and loss of glycosaminoglycans leads to abrasion of the articular cartilage and functional deterioration of the joint. This deformity and ongoing turnover of the cartilage matrix leads to pain, stiffness, joint swelling, and crepitus.

As many as 90% of individuals over age 40 show degenerative changes radiographically, although not all of these individuals have symptoms. OA is the most common form of arthritis and frequently affects hands knees, hips, and spine. OA is characterized as primary if there is no apparent predisposing cause or secondary if it is associated with an underlying medical condition. Primary OA can be localized to one or two joints or generalized to three or more joints. It often manifests when individuals are in their 50s and 60s.

Primary (idiopathic) OA is the most common form of the condition; risk factors for this from of OA are described below. Secondary OA follows the same pathology as primary. It is associated with trauma to or near the joint (acute or chronic), mechanical factors (e.g., unequal lower limb lengths), or an underlying metabolic or endocrine disorder (e.g., Wilson's disease, acromegaly, hemochromatosis, hypoparathyroidism), calcium deposition disease, neuropathic arthropathy (Charcot's joints), or other bone and joint diseases (Brandt 1998).

• Increasing age
• Genetic predisposition
• Obesity
• Trauma
• History of inflammatory joint disease
• Metabolic or endocrine disorders (e.g., hemochromatosis, acromegaly, calcium pyrophosphate deposition disease [CPPD])
• Congenital bone and joint disorders
• Repetitive stressful joint use, such as that associated with certain occupations (e.g., professional baseball, ballet dancing, factory and construction work)
• Crystalline deposition

• Morning stiffness or stiffness after inactivity for more than 15 minutes
• Localized joint pain (often described as a deep ache) (Brandt 1998), worsened by movement and improved with rest (in severe cases, constant pain); although night time pain is associated with advanced disease
• Soft tissue swelling
• Warmth to palpation
• Bony crepitus
• Synovial fluid
• Limited range of motion
• Muscle atrophy
• Subluxation
• Bony hypertrophy causing gross deformities (e.g., Heberden's nodules of distal interphalangeal joints)

Symptom relief, maintenance of mobility, and minimization of disability are the aims of treatment. A combination of conventional and complementary and alternative medicine (CAM) treatment modalities, including exercise, may provide the most effective outcomes.

Nonpharmacologic management should be the mainstay of treatment for OA. Palliative use of analgesics and anti-inflammatories are used adjunctively. In light of reactions to drug therapies, lifestyle approaches and many alternative medical therapies offering safe and effective options are being used. Various surveys conducted in 1997 showed that anywhere from 26% to 100% of patients with rheumatologic disorders had tried some form of CAM (Ernst and Chrubasik 2000). Several natural agents are at least as effective for symptom relief, and some show evidence of disease modification (Gaby 1999).

Some of the most promising nonpharmacologic and treatments for OA are as follows:

• Measures that reduce the load on the joint, such as posture modification and weight loss in obese individuals
• Lifestyle changes (exercise, in particular, but also the use of mobility aids and self-management education)
• Capsaicin cream 
• S-adenosylmethionine (SAMe)
• Glucosamine and/or chondroitin sulfates
• Antioxidants
• Phyto–anti-inflammatories
• Chiropractic
• Physical therapy and magnet therapy 
• Acupuncture
• Yoga
• Tai chi

Primary prevention strategies to lessen the likelihood of developing OA include the following (da Camara and Dowless 1998):

• Patient education
• Protection of an injured joint from further damage
• Exercise
• Weight reduction; in obese individuals, loss of 5 kg was associated with a 50% reduction in the odds of developing OA
• Avoidance of excessive repetitive motions

In one or more studies, S-adenosylmethionine (SAMe) prevented surgically-induced experimental OA in rabbits (di Pavoda 1987). The prophylactic use of SAMe in humans is unknown at this time.

Exercise

Exercise to stretch and relax muscles surrounding osteoarthritic joints as well as strength training for the same muscle groups is almost invariably included in the regimen for treating OA; however, strong evidence regarding the effectiveness of exercise for this condition is lacking (O'Reilly et al. 1999). O'Reilly et al. (1999) evaluated a home exercise program aimed at strengthening quadriceps to reduce pain and disability associated with OA of the knee. Those receiving the treatment of initial education followed by carrying out the assigned exercises at home were compared to a control group not receiving the exercise treatment:

• Western Ontario McMaster Osteoarthritis Index (WOMAC) scores showed a 22.5% reduction in pain in the treatment group compared with only 6.2% in the control group.
• Physical function scores were improved by 17.4% in the treatment group and did not change in the control group.

In addition, a systematic review of a small number of randomized controlled clinical trials conducted by van Baar et al. (1999) concluded that exercise therapy reduced pain and disability and improved walking in patients with OA of the knee or hip. For the purposes of the review, exercise therapy was defined as activities intended to improve strength, range of motion, balance, endurance, coordination, posture, motor function, and/or motor development. Because the studies reviewed had small sample sizes and other methodological flaws, van Baar et al. (1999) were unable to suggest whether certain types of exercise are more effective than others.

• Aspirin—as needed for inflammation and analgesia
• Acetaminophen—to reduce pain
• Nonsteroidal anti-inflammatory drugs (NSAIDs)—e.g., ibuprofen, naproxen sodium, diclofenac, etodolac, etc. to reduce pain and inflammation. Approximately 30% of peptic ulcer disease cases in the elderly (>65) can be attributed to NSAID use. Although still controversial, there is some evidence that NSAIDs may accelerate the progression of OA because they appear to inhibit cartilage repair.
• Cyclooxygenase 2 (COX-2) inhibitors—celecoxib and rofecoxib to reduce pain; reduced risk for gastrointestinal side effects; effect of long-term use unknown (Acevedo et al 2001)
• Tramadol—a weak opioid for refractory pain control
• Hyaluronic acid—a component of synovial fluid from which medications have been derived; may restore lubrication to the joints; intra-articular injections administered once per week under local anesthesia for 3 to 5 weeks; effects may last up to 1 year
• Intra-articular or peri-articular glucocorticoids—for symptomatic relief. Oral corticosteroids are not used for treatment of OA
• Misoprostol—reduces gastrointestinal bleeding associated with NSAID use

Glucosamine and Chondroitin

These naturally occurring compounds found in human cartilage and derived (for use in supplements) from bovine and calf cartilage (Deal and Moskowitz 1999), have been widely used in Europe for more than a decade and have also recently gained popularity in the United States. Both agents exhibit anti-inflammatory activities and favorably affect cartilage metabolism in vitro. To evaluate long-term efficacy and toxicity, the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH) has funded a large, parallel design, randomized, controlled clinical trial comparing glucosamine sulfate (500 mg tid), chondroitin sulfate (400 mg tid), a combination of the two agents, and placebo (Towheed and Anastassiades 2000). The study is projected to be complete by March 2005.

Several reviews of clinical trials examining either glucosamine or chondroitin sulfate for OA, collectively representing more than 600 subjects tested with chondroitin and nearly 3000 tested with glucosamine, concluded that these agents showed the benefits described below.

Glucosamine is administered orally or via intra-articular or intramuscular injection (da Camara and Dowless 1998; Deal and Moskowitz 1999; Delafuente 2000; Gaby 1999). It has been associated with:

• Decreased pain in comparison to both placebo and NSAIDs, particularly ibuprofen
• Longer time to onset of action than ibuprofen but pain control lasted longer
• Significantly fewer adverse effects than ibuprofen; in fact, lack of significant toxicity with short term oral use
• Significant improvement in Lequesne score, particularly in terms of pain and mobility, compared to both placebo and piroxicam. (Lequesne index is a standard measurement for OA that rates pain, immobility, walking distance, limitations on activities of daily living, stair walking, and squatting.)
• Longer maintenance of improved symptoms compared to piroxicam following discontinuation of treatment

While most of the trials identified used glucosamine sulfate, one study discussed by Deal and Moskowitz (1999) compared glucosamine hydrochloride to placebo in 89 patients with OA of the knee. Glucosamine hydrochloride is believed to have greater bioactivity than glucosamine sulfate (Deal and Moskowitz 1999). Since more research has been done on the sulfate of glucosamine, that is the form generally recommended.

Authors of the review articles discussed above were able to comment only on the short-term safety of glucosamine administration. A long-term study by Reginster et al. (2001) followed 212 patients with OA of the knee who were randomized to receive either oral glucosamine sulfate 1500 mg/day or placebo for 3 years. Primary outcome measures included tibiofemoral joint space measured radiographically and assessment of symptoms by the WOMAC osteoarthritis index. Secondary measures included rescue medication use, occurrence of adverse events, and routine laboratory tests administered to evaluate safety. The experimental and control groups were the same at baseline evaluation; the following statistically significant results were noted at the end of this landmark study:

• Compared to those in the glucosamine sulfate group, two times as many subjects receiving placebo had significant joint space narrowing.
• Those receiving glucosamine sulfate had a 20% to 25% improvement in symptoms (as measured by WOMAC) compared to (a slight worsening in the placebo group).

There was no difference in adverse event reports or laboratory tests on safety between the experimental and placebo groups (Reginster et al. 2001). The study authors were encouraged by the potential of glucosamine to be a disease modifier as evidenced by the protection from joint space narrowing determined radiographically; however, radiographic changes do not correlate to alterations in perceived pain or to physical function in patients with OA (McAlindon 2001). Furthermore, a glucosamine sulfate product marketed as a medication in Europe was used in this trial; the authors note that the results may or may not be generalizable to dietary supplements available in the United States (Reginster et al. 2001).

Chondroitin—randomized, controlled clinical trials have produced significant results demonstrating the following from chondroitin (Deal and Moskowitz 1999; Gaby 1999; Leeb et al. 2000):

• Lower NSAID and paracetamol intake compared to placebo
• Decreased pain compared to placebo by visual analogue scale (VAS) and Lequesne index
• Increased mobility, decreased swelling, decreased joint effusion, and decreased time to walk 20 meters compared to placebo
• Decreased pain after 30 days of chondroitin therapy compared to 10 days for diclofenac; whereas pain recurred very soon after cessation of diclofenac therapy, pain control lasted 3 months following discontinuation of chondroitin
• Attenuated progression of OA (determined radiographically) compared to placebo, suggesting a possible chondroprotective effect (i.e., chondroitin may slow degradation of and may even repair cartilage)

Deal and Moskowitz (1999) suggest that although glucosamine and chondroitin have been studied separately and together, and that glucosamine in particular may be effective alone, the combined use of glucosamine and chondroitin may be reasonable pending results of further research. They caution, however, that because glucosamine and chondroitin agents sold over-the-counter in the United States are not regulated by the U.S. Food and Drug Administration, preparations may not be properly standardized or contain what is listed on the label (Deal and Moskowitz 1999).

A meta-analysis of randomized, placebo-controlled, double-blinded clinical trials on glucosamine and chondroitin (McAlindon et al. 2000) also demonstrated moderate to large effects for each of these substances compared to placebo. Studies included in the analysis had to have lasted 4 weeks (the approximate time for onset of action for both glucosamine and chondroitin) or more. After evaluating 37 trials, 15 met the inclusion criteria. All of the trials used one or more standard measurements for OA:

Although the reviewers felt that flawed study designs disallowed definitive evaluation, they concluded that these agents are likely to have some efficacy and to be safe (McAlindon et al. 2000).

S-adenosylmethionine (SAMe)

Although its mechanism of action remains unclear, SAMe has been shown to exhibit analgesic and anti-inflammatory properties in laboratory and animal studies (di Pavoda 1987; Domljan et al. 1989). Randomized controlled clinical trials of human subjects (although they are generally small in size and of short duration) show favorable results for SAMe when it is used to ameliorate symptoms of OA. These positive outcomes suggest that SAMe has promise; well-controlled, large scale, long-term studies are needed to confirm preliminary findings.

In several short-term (4 to 12 weeks) randomized controlled clinical trials, oral SAMe (1200 mg/day in three divided doses) compared favorably to NSAIDs (including ibuprofen, indomethicin, naproxyn, and piroxicam) in adults with knee, hip, or spine OA in the following ways (Domljan et al. 1989; Maccagno et al. 1987; Müller-Fassbender 1987; Vetter 1987):

• Diminished morning stiffness
• Decreased pain
• Reduced swelling
• Less palpable crepitus on exam
• Improved range of motion
• Shortened amount of time to walk 10 meters

In addition, in the trial comparing SAMe to the NSAID indomethacin (Vetter 1987), significantly fewer subjects taking SAMe complained of adverse effects; this difference in tolerability was not demonstrated in the three other studies mentioned.

In an extensive review of trials conducted with SAMe, including one long-term (24 month) human study, and clinical trials collectively representing 22,000 subjects, di Padova (1987) concluded that SAMe supplementation was associated with the following benefits:

• Symptomatic improvement in the majority of patients, measured both subjectively and objectively
• High tolerance without gastrointestinal or systemic side effects (including no known adverse effects to renal, hepatobiliary, hematopoietic, or cardiovascular systems) (Bradley et al. 1994)
• No negative influences on cartilage production; in fact, SAMe has been shown to promote proteoglycan synthesis in vitro, a step necessary for cartilage repair, as opposed to NSAIDs which appear to inhibit proteoglycan synthesis
• Safety of use and effectiveness over an extended period of time
• Reduction in disease relapse

Intravenous loading with SAMe may be beneficial prior to oral maintenance (Bradley et al. 1994).

Vitamin D

Vitamin D is essential to normal bone and cartilage metabolism through bone mineralization and cell differentiation (Sowers and Lachance 1999).

Studies evaluating vitamin D use for OA have made the following reports:

• In vitro, vitamin D stimulates proteoglycan synthesis by mature chondrocytes and modulates activity of the cartilage degrading enzyme metalloproteinase (Lane et al. 1999).
• For male and female patients with knee OA who participated in the 1996 Framingham Heart Study, the risk of radiographic progression increased threefold in the middle and lower tertiles for vitamin D intake (3 to 170 IU/day) and 25-hydroxyvitamin D (25-OH vitamin D) serum levels (4.9 to 24 ng/mL) compared to the highest tertile of dietary intake (400 to 1600 IU) and serum vitamin D levels (36 to 79 ng/mL). Vitamin D intake and 25-vitamin D serum levels did not correlate to de novo development of OA (McAlindon et al. 1996a).
• In a longitudinal study, women older than 65 years in the low (8 to 22 ng/mL) and mid-range (23 to 29 ng/mL) tertiles for serum levels of 25-vitamin D showed a significantly higher risk of having developed hip OA (as ascertained by radiographic measurement) at the 8-year follow-up than those in the highest tertile (30 to 72 ng/mL). No such correlation was found with 1,25-dihydroxyvitamin D. Possible explanations for the different results are that: First, serum 25-vitamin D is a better indicator of dietary intake and tissue stores of vitamin D because it has a longer half-life than 1,25-vitamin D (Lane et al. 1999); second, 1,25-vitamin D may actually inhibit collagen synthesis and promote bone resorption (Sowers and Lachance 1999).

Antioxidants—Vitamins A, C, and E, and Beta-Carotene

Antioxidants appear to significantly modulate the oxidative stress and inflammatory processes attributed to reactive oxygen species (ROS); they may therefore impede the progression of OA (Sowers and Lachance 1999). ROS may be generated in joints, and has been implicated in many degenerative changes in the aging body including destruction of cartilage and connective tissue (McAlindon et al. 1996a; Sowers and Lachance 1999). Evidence regarding antioxidants remains primarily anecdotal, however; it will be important to determine the roles of individual antioxidant vitamins and recognize their interdependency in order to substantiate the evidence (Sowers and Lachance 1999).

• Vitamin A and Beta-Carotene

Vitamin A occurs naturally in two forms: 1) retinol, which is fat-soluble and usually derived from animal tissue, and 2) beta-carotene, a water-soluble precursor derived from plants and ultimately converted by the liver to retinol. Because of their antioxidant effects, vitamin A and beta-carotene have at least a theoretical role in ameliorating OA. In addition, vitamin A serves an essential role in bone development. Although the role of these micronutrients for OA has not been adequately studied (Sowers and Lachance 1999), epidemiologic evidence suggests a possible connection. In the Framingham OA Cohort Study, McAlindon et al (1996a) reported a twofold reduction in risk of progression and reduced risk of knee pain for patients in the highest tertile of beta-carotene intake.

• Vitamin C

Vitamin C acts as an electron donor in the synthesis of type II collagen (a major component of cartilage) and its absence may cause reduced resilience of collagen fibrils and increased turnover rates (McAlindon et al. 1996a). This vitamin is also a carrier of sulfate groups essential to the synthesis of glycosaminoglycan. Because one of the earliest signs of OA is depletion of sulfated proteoglycans from the extracellular matrix of articular cartilage, low levels of vitamin C may be implicated in this aspect of the disease (Sowers and Lachance 1999).

In the Framingham OA Cohort Study, patients in the middle and highest tertiles of vitamin C intake showed the following positive outcomes (McAlindon et al. 1996a):

• A threefold reduction in risk of progression of OA (measured as radiographic joint space narrowing as an indication of cartilage loss); the group in the lowest tertile had a fourfold increase in risk
• A substantially lowered risk of knee pain

Intake of vitamin C in this trial did not correlate to new onset of OA (McAlindon et al. 1996a).

Guinea pigs (who, like humans, have an absolute requirement for vitamin C) fed a diet high in vitamin C prior to experimental induction of OA developed less severe disease than those fed a diet low in vitamin C (Sowers and Lachance 1999).

• Vitamin E

The precise mechanism of action of vitamin E against OA is not known. It is theorized that the positive effect may be due to the inhibition of prostaglandin synthesis and stabilization of lysosomal membranes; this action reduces the release of enzymes (e.g., metalloproteinase) that play a role in the pathogenesis of joint damage (Gaby 1999). The following has been reported about vitamin E:

• In a crossover study, vitamin E provided marked pain relief in 52% of patients receiving 600 mg/day (equivalent to 900 IU/day) for 10 days compared to 4% in the placebo group; the difference was statistically significant (Machtey and Ouaknine 1978).
• In a 1990 study, 53 patients with knee or hip OA were randomized to receive 600 IU tid of vitamin E or diclofenac 50 mg tid; both groups demonstrated equal success in reducing knee effusions and walking time, and increasing joint mobility (Gaby 1999).
• In the Framingham OA Cohort Study, vitamin E intake was associated with some reduction in risk of disease progression in the male subgroup only (McAlindon et al. 1996a).

Niacinamide

A pilot study of 72 patients with OA randomly assigned to receive niacinamide, a form of vitamin B3, showed an overall improvement rate of 29% in the treatment group compared to a worsening by 10% in the placebo group, as measured by the Arthritis Impact Measurement Scale (AIMS); the difference was statistically significant (Jonas et al. 1996). At a dosage level of 3000 mg/day taken in six divided doses for 12 weeks, the following statistically significant positive results for those receiving niacinamide were noted:

• Improved joint mobility
• Reduced erythrocyte sedimentation rate by 22%, a non-specific measurement of inflammation
• Reduced need for anti-inflammatory medications by 13% compared to a slightly increased need in the placebo group

The authors speculate that niacinamide may actually contribute to cartilage repair and may be used safely with NSAIDs to complement the drugs' anti-inflammatory actions (Jonas et al. 1996). Niacinamide generally has a delayed onset of action of 3 to 4 weeks, with the greatest improvement believed to occur after continual treatment for 1 to 3 years; experts feel that this supports the idea that niacinamide controls OA, as opposed to merely ameliorating the inflammatory effects of the disease process (Gaby 1999). Further research is required to determine if the results of the pilot are applicable to a larger population, and to establish the mechanism of action by which niacinamide confers its benefit for OA (Gaby 1999; Jonas et al. 1996).

Omega-3 Fatty Acids

Clinical research regarding use of omega-3 fatty acid dietary supplements for inflammatory joint conditions has focused almost entirely on rheumatoid arthritis (Kremer 2000; Simopoulos 1999). There is a theoretical benefit (supported by in vitro studies) for those with other inflammatory disorders such as OA to increasing omega-3 fatty acid in the diet, and swaying the balance away from omega-6 fatty acids (Danao-Camara and Shintani 1999). These in vitro studies have shown that incorporating omega-3 fatty acids (but not other polyunsaturated fatty acids [PUFAs] or saturated fatty acids) into chondrocytes of articular cartilage result in the following (Curtis et al. 2000):

• Reduced activity of proteoglycan degrading enzymes
• Decreased expression of inflammatory cytokines such as interleukin-1 and tumor necrosis factor

Omega-3 fatty acids may generally be obtained from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (found in fish oils) and alpha-linolenic acid (found in green leafy vegetables, flaxseed, rapeseed, and walnuts) (Simopoulos 1999).

Another potential source of omega-3 fatty acids is New Zealand green lipped mussels (Perna canaliculus), used for centuries by the Maories for good health (Gibson and Gibson1998; Halpern 2000). In a double-blind, placebo-controlled trial (n=38) involving patients with OA, 39% of those treated with P. canaliculus experienced:

• Decreased joint stiffness and pain
• Increased grip strength
• Diminished time to walk 15 meters

Ten percent of patients experienced transient aggravation of symptoms. P. canaliculus comes in two different preparations, powder and lipid extracts. The more recently derived lipid extract lacks the risk of allergic response to shellfish as may be seen with the powder version (Gibson and Gibson1998). In addition, omega-3 essential fatty acid is concentrated in the oily portion of the mussel. Furthermore, the potency of the powder extract varies considerably (Halpern 2000).

Manganese

Manganese is a cofactor necessary for the synthesis of proteoglycans. In the first clinical trial in the United States studying glucosamine hydrochloride, sodium chondroitin sulfate, and manganese ascorbate, 72 patients with radiographically mild to moderate OA of the knee showed significant improvement in Lequesne index of symptoms when taking these supplements in combination (available commercially) compared to placebo. No serious side effects were reported. Those with radiographically severe disease, however, showed no significant improvement in Lequesne index. The study authors noted that the latter result was not surprising, given that the action of these supplements depends on the existence of some cartilage (Das and Hammad 2000). While it is not possible to know from this trial whether manganese contributed benefits beyond that of glucosamine and/or chondroitin, Das and Hammad (2000) note that:

• An estimated 37% of Americans have low levels of manganese in their diets
• Earlier studies have implicated manganese as a contributing factor to degenerative joint conditions and bone loss

Bromelain and other enzymes

An oral enzyme preparation containing 90 mg Ananas comosus (bromelain), 48 mg trypsin, and 100 mg rutin was compared to the NSAID diclofenac. In this study of 73 randomly assigned subjects, the two agents were shown to be equally effective in controlling knee pain and improving function as measured by both the Lequesne index and a VAS of pain (Klein and Kullich 2000).

Boron

Boron, a trace element found in soil and essential to plant life, plays a role in the synthesis of steroid hormones and vitamin D (Gaby 1999). There is a potential role for boron in the treatment of OA, which is suggested by the following information (Newnham 1994):

• Lower concentration of boron in the bones and synovial fluid of people with arthritis
• Higher incidence of OA in areas of the world with low boron intake (20% to 70% where intake is less than 1.0 mg/day; 0% to10% where intake is 3 to 10 mg/day)
• Decrease in inflammation in rats with experimentally induced OA in response to boron administration
• Symptomatic and clinical improvement in joint mobility and pain in 50% of patients treated with boron compared with 10% treated with placebo—in this study, 20 patients were randomly assigned to receive boron 6 mg/day (as sodium tetraborate decahydrate) or placebo for 8 weeks. The overall trend was not statistically significant, however; this may be attributable to the small sample size.

Collagen Hydrolysate

Hydrolyzed collagen contains amino acids important to the synthesis of collagen. In theory, the administration of this supplement, regarded as safe and nontoxic, could stimulate chondrocytes to synthesize the collagen matrix. There are reports of reduced pain in subjects with OA of the knee or hip given 10 g/day of collagen hydrolysate for 60 days. A double blind, randomized controlled clinical trial to test this hypothesis and the clinical efficacy of collagen hydrolysate is in progress (Deal and Moskowitz 1999).

Herbal remedies are among the most popular alternative therapies used by arthritis patients. Reasons are multifactorial but possibly include the desire to explore all options and avoid the side effects associated with conventional treatment. Not all herbal remedies are free of side effects themselves and, in most instances, the mechanism of action is unknown. Further, evidence for the effectiveness of many herbs is often anecdotal or based on historical knowledge. In randomized controlled clinical trials done to date, however, significant beneficial results were attributed to the following phyto-anti-inflammatories (Ernst and Chrubasik 2000):

• Harpagophytum procumbens (devil's claw) extract—anti-inflammatory, mild analgesic properties
• Salix spp. (willow bark)—analgesic, antipyrectic, and anti-inflammatory activity
• Urtica dioica (stinging nettle)—may enhance the antirheumatic effect of NSAIDs
• A fixed herbal combination of Populus tremula (aspen), Fraxinus excelsior (ash), and Solidago viraurea (goldenrod)
• Extracts of Withania somnifera (ashwagandha), Boswellia serrata (boswellia), and Curcuma longa (turmeric) (purported to have cyclooxygenase inhibitory properties)—an Ayurvedic herbal mixture
• Extracts of Salix spp. (willow bark), Cimicifuga racemosa (black cohosh), Smilax spp. (sarsaparilla), Guaiacum officinale (guaiacum) resin, and Populus tremuloides (poplar) bark used in combination

Capsicum frutescens (Capsaicin)

Capsaicin is the principle component in hot chilli peppers (also known as cayenne). Applied topically, it is believed to stimulate unmyelinated C fiber afferent neurons that release substance P (implicated in inflammation and pain in arthritis). Prolonged application of capsaicin depletes stores of substance P from sensory nerve endings, reducing or abolishing transmission of pain to higher centers (Rains and Bryson 1998). In a meta-analysis, it was found that capsaicin cream provided superior pain relief over placebo (Zhang and Li Wan Po 1994). Little to no improvement in joint swelling, grip strength, or functional capacity has been reported. Pain reduction generally begins 3 to 7 days following the start of capsaicin cream administration (Rosenstein 1999).

Avocado/Soybean Extracts

Following encouraging results from in vitro studies that showed inhibition of particular interleukins and stimulation of collagen synthesis in chondrocytes by avocado/soybean extracts (mixed in a ratio of 1/3 avocado oil and 2/3 soybean oil) as well as reduced NSAID use in a small pilot study of human subjects taking this supplement, Maheu et al. (1998) conducted a randomized controlled clinical trial of this extract. One hundred sixty four subjects between the ages of 45 and 75 with symptomatic OA of the knee or hip were randomized to receive either 300 mg avocado/soybean extract/day or placebo for 6 months with continued follow-up for 8 months. The treatment group showed the following improvements compared to placebo:

• Statistically significant reduction of pain, increase in mobility, and diminished disability at 6 and 8 months
• Less NSAID use in the treatment group compared to placebo at month 6 which nearly reached statistical significance (P=0.054), despite similar NSAID use for both groups at baseline
• Good to excellent tolerance in most patients receiving the avocado/soybean oil extract

Zingiber officinale (Ginger)

Ginger extract has long been used in traditional medical practices (such as Ayurvedic and Chinese) to diminish inflammation, including joint inflammatory processes. The traditional treatment has had many anecdotal successes and there have been a few case reports of benefit for OA in the literature (Srivastava and Mustafa 1992). However, a randomized, controlled clinical trial comparing an extract of Chinese ginger showed no significant benefit overall compared to ibuprofen and placebo (Bliddal et al. 2000).

Piper methysticum (Kava Kava)

Kava has traditionally been used as an analgesic; however, few studies have evaluated such effects. Animal studies suggest that kava may have significant analgesic properties, possibly via non-opiate pathways (Jamieson and Duffield 1990).

Salix spp. (Willow Bark)

In a meta-analysis of phyto-anti-inflammatories, two studies investigated the effects of willow bark (Ernst and Chrubasik 2000). In a 2-week pilot study comparing willow bark extract (standardized to 11% salicin content, equivalent to 240 mg salicin/day) to placebo in patients with cervical or lumbar arthritis, willow bark led to significantly greater improvement in Western Ontario MacMaster University Index (WOMAC) scrores. Another, larger study using a similar willow bark extract looked at its effects on OA of the knee or hip joint. This 2-week study also found significant positive effects for the willow bark group, as reflected in WOMAC scores.

Acupuncture appears to relieve pain by activating the gate-control system leading to the stimulation of large nerve fibers while suppressing small nerve fibers carrying pain signals to the spinal cord, and/or by stimulating the release of neurochemicals in the central nervous system (Felson et al. 2000). According to a review by Berman et al. (2000), several controlled trials suggest that this ancient Chinese practice is an effective therapy for pain associated with OA as well as for other aspects of the condition:

• In six randomized controlled clinical trials that collectively studied 169 persons with OA of the hip, knee, shoulder, neck, or hand, participants experienced significant reductions in pain compared to no-treatment, wait-list, or placebo medication controls.
• In 29 patients awaiting arthroplasty for knee OA, acupuncture significantly improved knee function, stair climbing ability, and walking time compared to wait-list controls.
• Fifty-eight OA patients receiving acupuncture in addition to standard NSAID therapy had lower pain and disability scores compared to controls receiving NSAIDs only.
• Sham acupuncture control groups did as well in terms of pain reduction as those receiving true acupuncture
• Compared to the NSAID piroxicam, better pain relief was reported in 32 OA subjects randomized to receive acupuncture

The NIH is funding a large multicenter clinical trial due to be completed in 2001, to fully evaluate the efficacy, safety, and cost-effectiveness of acupuncture for OA (Felson et al. 2000).

There is no evidence that spinal manipulation can reverse the joint degeneration that characterizes osteoarthritis (OA). However, spinal manipulation has been extensively researched in controlled clinical trials and shown to successfully treat the radicular pain that may be associated with spinal OA. In a literature review, Gottlieb (1997) found that chiropractic treatment.

• Increases intersegmental joint range of motion
• Restores normal movement of the spine, thereby improving both biomechanical and neurological function
• Relaxes hypertonic muscles
• Improves joint coordination
• Reduces pain

The reviewers concluded that chiropractic manipulation, especially combined with glucosamine supplementation and rehabilitative stretches and exercise to maintain joint function, is an effective adjuvant treatment for OA (Gottlieb 1997). According to chiropractic guidelines, "degenerative joint disease, osteoarthritis, degenerative discopathy and spondyloarthrosis are not contraindications to high velocity thrust procedures to the area of pathology but treatment modification may be warranted during active inflammatory phases" (Chopra 2000). The frequency of chiropractic adjustment required varies from one individual to the next.

Physical Therapy

Manual therapy and supervised exercise may decrease or delay the need for surgery in patients with OA. In a randomized, controlled clinical trial evaluating physical therapy and exercise in OA of the knee, the treatment group received manual therapy to the lumbar spine, hip, knee, and ankle, while the placebo group received subtherapeutic ultrasound to the knee. The treatment group showed clinical and statistically significant improvement in the following (Deyle et al. 2000):

• Stiffness
• Self-reported pain
• Functional ability
• Walking distance
• Osteoarthritis WOMAC index scores
• Requirement for knee arthroplasty (5% of those in the treatment group had undergone this surgery by the end of 1 year compared to 20% in the control group)

Balneotherapy (Hydrotherapy or Spa Therapy)

This is one of the oldest forms of therapy for pain relief for people with OA, and there are many anecdotal claims of its benefit. "Balneo" comes from the Latin word for bath (balneum) and refers to bathing in thermal or mineral waters; however, hydrotherapy, which can be performed under the guidance of certain physical therapists is occasionally used interchangeably with the word balneotherapy (Verhagen et al. 2000). The goals of balneotherapy for arthritis include:

• Improvement in range of joint motion
• Increasing muscle strength
• Elimination of muscle spasm
• Enhancement of functional mobility
• Easing pain

While balneotherapy is most often used for psoriatic or rheumatoid arthritis, there is at least a theoretic benefit for OA as well. An overview of 10 studies of balneotherapy for different types of arthritis reported some positive findings, including pain relief in four out of the 10 trials and enhanced quality of life in two (Verhagen et al. 2000). However, the review authors noted that methodological flaws in all of the studies and inadequate statistical analyses make it difficult to draw scientific conclusions about the value of balneotherapy for arthritis; they stress the importance of adequate controlled clinical trials to distinguish between the benefit of the spa environment vs. the actual water treatments.

Magnet Therapy

Exposure to electromagnetic fields has been shown to increase proliferation of chondrocytes and synthesis of proteoglycans in vitro; one important study confirmed that low-energy AC and DC magnetic fields stimulated articular cartilage metabolism (Trock 2000). Magnets for therapeutic purposes can essentially be applied in one of two ways:

• Contact with skin surface over the target tissue (e.g., bone, joint, wound); this is called Capacitive coupling
• Pulsed electomagnetic fields (PEMFs), which induce an electrical current in the target tissue without direct contact to the body; this is called Inductive coupling

Studies using either type of magnet therapy for arthritis are scarce and the few that exist have mainly been open, nonrandomized, and uncontrolled. However, in one randomized, placebo controlled study of 78 patients with chronic knee OA, delivery of a 100 Hz low amplitude signal to the knee joint via skin surface electrodes for 6 to 10 hours qd for 4 weeks led to significant reduction in pain compared to placebo. The method may also be more cost effective than current conventional treatment for arthritis. Similar results of diminished pain and enhanced function have been attributed to the PEMF method as well as in an open trial of 86 patients with knee OA (Trock 2000).

Ice Massage, Transcutaneous Nerve Stimulation (TENS), and Electroacupuncture

In a placebo-controlled study (n=100) comparing the effectiveness of TENS, electroacupuncture, and ice massage for the treatment of OA of the knee, each of the three methods were found to be superior to placebo and to (Yurtkuran and Kocagil 1999):

• Reduce pain at rest
• Reduce stiffness
• Increase 50 foot walking time
• Increase quadriceps muscle strength
• Increase degree of knee flexion

Patients with OA are best treated with an individualized homeopathic medicine chosen by a professional homeopath. However, several studies have found positive results compared with various conventional drugs when using homeopathic combination (formula) products.

According to a review of four different adequately-designed, randomized, controlled clinical trials, homeopathy may be at least as effective as some standard therapies used for OA (Long and Ernst 2001).

• A topical homeopathic gel containing Symphytum officinale (comfrey), Rhus toxicodendron (poison ivy), and Ledum palustre (marsh-tea), was at least as effective as topical piroxicam gel for pain reduction (van Haselen and Fisher 2000).
• Another combination homeopathic preparation containing R. toxicodendron, Arnica montana (arnica), Solanum dulcamara (climbing nightshade), Sanguinaria canadensis (bloodroot), and Sulphur was compared to hyaluronic acid (both administered by injection); improvement in symptoms was shown with the homeopathic remedy.
• An oral administration of a liquid homeopathic preparation containing R. toxicodendron, Causticum (potassium hydrate), and Lac vaccinum (cow's milk) compared to a liquid preparation of paracetamol revealed a trend toward greater reductions of pain in the group receiving the homeopathic remedy; this difference was not statistically significant (Shealy et al. 1998).

Not all results of studies evaluating homeopathic remedies were positive. Comparison of R. toxicodendron to placebo and to fenoprofen for pain control found that R. toxicodendron was no more effective than placebo in reducing pain while fenoprofen was significantly more effective than both the homeopathic remedy and placebo (Long and Ernst 2001; Shipley et al. 1983). However, this study may be of questionable value because it tested a single homeopathic medicine without adequate individualization of symptoms.

Some common homeopathic medicines for OA are as follows (Morrison 1998):

• Calcarea carbonica 
• Bryonia
• Causticum
• Graphites
• Guaiacum 

Chronic pain and disability can make daily functioning difficult. A holistic approach to care in these clinical circumstances may positively affect lifestyle. Several factors influence the subjective experience of pain—these include level of social support, psychological comorbidity, functional status, coping strategies, pain threshold, and age. In a study comparing individuals aged >65 to those aged <65, age appeared to be indicative of not only the experience of pain itself but also of choices regarding how to combat the pain. The older group reported that applying heat, resting, and taking prescribed medication (in descending order) were most helpful. The younger group found relaxation techniques such as guided imagery and meditation significantly more helpful, and were more inclined than their older counterparts to use these methods along with massage and support groups. The authors of this study concluded that the younger group had had more exposure to such alternatives, and that this could account for the observed differences. Also, compared to the younger group, the older group may have more limited access to financial and other resources such as transportation and guidance in planning from healthcare providers. The authors suggest that the nonpharmacologic methods preferred by the younger group should be considered by older adults, particularly because this population is at greater risk for side effects and interactions from medications (Davis et al. 1990).

Yoga

This ancient Indian practice is well known for its physical, psychological, emotional, and spiritual benefits and is often recommended in the West to relieve musculoskeletal symptoms. In one clinical trial studying OA of the hand, the group practicing yoga showed a significant decrease in pain and improved range of motion compared to those participating in nonyoga stretching and strengthening sessions (Garfinkel et al. 1994). Certain yoga "asanas" (postures) strengthen the quadriceps and emphasize stretching, both of which benefit patients with knee OA. The authors caution that in those with arthritis, asanas should be introduced slowly and only performed after an appropriate warm-up; yoga is best performed under the careful guidance of an appropriate instructor (Garfinkel and Schumacher 2000).

Herbal Remedies

A recent randomized controlled clinical trial comparing Ayurvedic herbal remedies with placebo showed significant improvement in pain and disability in the treatment group, with only mild side effects (Chopra 2000).

• A combination preparation containing Withania somnifera (winter cherry) root 900 mg, Boswellia serrata (boswellia) stem 200 mg, Curcuma longa (turmeric) rhizome 100 mg, and zinc (oxidized to ash) 100 mg administered in capsule form tid significantly reduced pain and disability. Side effects included nausea, dermatitis, and stomach pain (Gaby 1999; Kulkarni et al. 1991)

Tai Chi

This ancient form of classical conditioning practiced in China for centuries has been shown to provide the following benefits (Hartman et al. 2000):

• Improved fitness
• Increased muscular strength
• Enhanced flexibility
• Reduced percentage of body fat
• Diminished risk of falls in the elderly

In a 12-week, randomized controlled clinical trial, 33 subjects with OA of the knee or hip and ranging in age from 49 to 81 years old either practiced tai chi (two 1-hour classes per week) or continued their usual routine of physical activity and met as a group three times to eat and share experiences (Hartman et al. 2000). The group receiving tai chi classes demonstrated significant positive changes in the following areas compared to the controls:

• Improved overall sense of quality of life
• Diminished feelings of stress/tension
• Increased satisfaction with general health
• Decreased fatigue
• Easier self-management of arthritis symptoms (the authors attribute this to the sense of confidence that tai chi can foster)

While measures of pain and physical function showed a trend toward improvement in the group practicing tai chi, the changes were not statistically significant compared to controls. The authors note that another advantage of tai chi for this population is that classes may be tailored to a wide range of participants including those with severe limitations such as obesity, and those using a walker or portable oxygen (Hartman et al. 2000).

Surgery is usually considered only if nonsurgical treatment fails. Options include:

• Osteotomy may alleviate pain and peak dynamic loading in those with moderately advanced knee or hip OA.
• Arthroscopic debridement and lavage may reduce symptoms, particularly when degenerative meniscal tears combine with mechanical symptoms. The effectiveness of lavage over placebo has not been proven.
• Arthrodesis (joint fusion) may be considered for the spine and small joints of the carpus, hand, and foot.
• Arthroplasty (joint replacement) may be the most successful medical intervention for patients with advanced, unresponsive OA, particularly for older people due to its limited durability (approximately 20 years). Research is aimed at developing materials to enhance durability (Felson et al. 2000).

Other procedures are also being used with differing levels of success:

• Biological restoration of articular cartilage loss using growth factors or enhancement of bone marrow progenitor cells
• Hemicallotasis lessens knee deformity by keeping the joint stable over a period of several weeks (via an external frame attached to the joint with pins).

Cartilage transplantation: Osteochondral autografts of small chondral lesions produces clinically good outcomes in 91% of patients; Osteochondral allografts produce a 75% success rate at 5 years and 64% at 10 years. (Articular cartilage loss is often too large for long-term success with these procedures.); Tissue engineering using autologous chondrocyte therapy shows clinical improvement in 90% of patients at 2 to 9 years of follow-up; however, long-term success remains in doubt (Felson et al. 2000).

• Loss of independent ambulation due to hip or knee OA
• Gastrointestinal bleeding and decreased renal function with long-term NSAID and aspirin use, particularly in the elderly.

While OA can be a debilitating condition, current treatment methods have shown great promise in reducing pain and improving mobility; therefore, many are able to achieve disease stabilization and avoid chronic progression. Joint deterioration in OA tends to be slower than that of rheumatoid arthritis. Still, knee OA is the number one cause of disability in industrialized countries. Joint effusions and joint enlargement occur later in the course of the disease. In some cases, joint replacement (e.g., hip) may become necessary. Most advanced stages include full cartilage loss.

Most women who become pregnant are normally too young to have primary OA. Many of the herbs used in treatment for OA have not been tested on pregnant women; therefore, caution is advised when suggesting their use, which is best directed by an herbal specialist, with regular follow up to the obstetrician.

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