A Novel Approach In The Treatment of Arthritis

Suprising new discoveries reveal the underlying cause of age-related cartilage breakdown and what can be done about it

Osteoarthritis & Rheumatoid Arthritis

What's the difference?
Can arthritis be prevented or cured?
New research is shedding light on old, natural remedies and opening up new treatment possibilities.

Arthritis is all too well known by most of us as a source of discomfort and pain. There are different forms of arthritis, however, with distinctive symptoms and prognosis.

Osteoarthritis is the most common form. It is the kind that seems to come with the wear-and-tear process of aging, affecting approximately 70-80% of the population over age 50. The onset is marked by morning stiffness, crackling joints and perhaps some pain. As it gets worse it causes discomfort, pain and disability in varying degrees for millions of people. It also causes an enormous consumption of painkillers and anti-inflammatory drugs that many times have undesirable long-term effects. Does it have to be this bad?

Modern medicine does not have much to offer for these chronic conditions, only symptomatic, temporary relief. Painkillers and the so called NSAIDs, non-steroidal anti-inflammatory drugs, are effective in reducing symptoms quickly but often cause serious side effects such as ulcers and gastrointestinal bleeding, and do not stop the progression of the disease. In the long run they have actually proven to worsen the condition by accelerating joint destruction.

The last few years of research, however, have brought some hope to this dismal picture. Old herbal remedies such as ginger, nettle and willow bark, as well as fish oils and the already well known cartilage constituents glucosamine sulphate and chondroitin sulphate, are about to revolutionize the treatment of arthritis. These substances not only give symptomatic relief but actually intervene at the root of the problem and help the body to rebuild functioning joints.

Osteoarthritis
Osteoarthritis(OA)/arthrosis is a disease mainly characterized by degenerative processes of the articular cartilage, but changes also involve the synovial membrane and the bone next to the cartilage. It is a gradual decay that most often affects the weight bearing joints (knees, hips and spinal joints) and the joints of the hand. A breakdown of the cartilage matrix leads to cracks and ulcers and a thinning of the cartilage with a loss of shock absorption. The underlying bone starts to thicken as a response to the increasing stress and bone spurs are formed. In the advanced phases of osteoarthritis, an inflammatory reaction in the synovial membrane can be seen. This severe degeneration causes pain, swelling, deformation and reduced range of motion.

Traditionally osteoarthritis has been connected to aging, obesity and repeated mechanical joint stress. Predisposing factors ch as trauma or inherited abnormalities are also known to trigger degenerative changes and cause secondary osteoarthritis at even younger ages. New research is beginning to shed light on how osteoarthritis develops at the cellular and molecular levels.

Evidence is accumulating that the culprits may be factors called cytokines together with enzymes that break down the collagen trix. Cytokines are proteins that carry messages between cells and regulate immunity and inflammation. Two cytokines, tumor necrosis factor alpha (TNF-a) and interleukin one beta (IL-1b), play an essential role in the cartilage destruction and inflammation process (Feldman et al., 1996). They have been found in elevated levels in both the synovial membrane, the synovial fluid and the cartilage of osteoarthritis patients. In animal models it was shown that inhibition of TNF-a results in decreased inflammation, while inhibition of IL-1b effectively prevents cartilage destruction (Plows D et al., 1995).

TNF-a has proven to be an even more important factor in rheumatoid arthritis (RA), where it is a key factor in promoting inflammation and damage to cartilage and bone (Bertolini et al, 1986; Saklatvala J, 1986).

Rheumatoid arthritis
Unlike osteoarthritis, RA is a so-called autoimmune disease, characterized by chronic inflammation and thickening of the synovial lining in addition to cartilage destruction. In autoimmune diseases the immune system attacks body tissues as if they were foreign invaders. As in most other chronic inflammatory diseases, the etiology and pathogenesis of RA is poorly understood. Contributing factors are thought to include food allergies, leaky gut syndrome, hereditary factors and microbes.

RA affects approximately 3% of the population, striking women three times as often as men. The typical onset is at the age of 20-40. The clinical picture varies from mild chronic joint inflammation with occasional flare-ups to painfully deformed joints. The disease is often accompanied by low-grade fever, weight loss and a general feeling of sickness and soreness.

Biochemical mechanisms
The destruction of cartilage and bone in both OA and RA is currently believed to be due mainly to the action of matrix enzymes (metalloproteinases), which include collagenases and stromelysins (Birkedal-Hansen H et al., 1993; Hill et al., 1994). These enzymes are under the control of cytokines such as IL-1b and TNF-a, which are known to be highly activated in rheumatoid arthritis. Some of the enzymes have pro-inflammatory characteristics and some have anti-inflammatory properties. The varying balance between these forces probably accounts for the variation in disease activity as it flares up and subsides.

Inflammation is a living tissue response to mechanical, chemical and immunological challenge. It is characterized by high levels of arachidonic acid metabolites, which are metabolized along two different enzymatic pathways: cyclooxygenase and lipoxygenase, leading to prostaglandin PGE2 and leukotriene LTB4, which are the most prominent metabolites and important mediators of inflammation (Srivastava KC et al., 1992). They play a crucial role in arthritis by causing resorption of bone, stimulating the secretion of collagenase and inhibiting the formation of proteoglycans.

Data from many studies confirm the important role of TNF-a in regulating production of both inflammatory and anti-inflammatory mediators in RA. Because of the demonstrated excess of pro-inflammatory cytokines, such as TNF-a, it was hypothesized that a blockade of TNF-a should be beneficial. Several experimental as well as clinical studies have been conducted with anti-TNF-a antibody. (Paulus HE et al., 1990). The results have confirmed that TNF-a is a good therapeutic target in RA.

A placebo-controlled trial by Feldman et al. (1997), provided the first convincing evidence that blockade of a specific cytokine could be effective treatment in human autoimmune or inflammatory diseases. Interesting results with TNF-a blockade have also been achieved in trials conducted on Crohn's disease, sepsis and HIV/AIDS.

The effectiveness and reproducibility of short-term anti-TNF-a antibody therapy, which has severe limitations, has stimulated the development of more convenient and practical alternatives to this kind of therapy. Interestingly enough, the leaf of the common nettle plant has recently been shown to lower TNF-a levels.

Nettle Leaf (Urtica Dioica)
Nettle leaf is an herb that has a long tradition of use as an adjuvant remedy in the treatment of arthritis in Germany. Nettle leaf extract has recently been found to contain a variety of active compounds, such as cyclooxygenase and lipoxygenase inhibitors and substances that affect cytokine secretion (Obertreis et al., 1996; Teucher et al., 1996).

Not only does nettle leaf reduce TNF-a levels, as mentioned above, but it has recently been demonstrated that it does so by potently inhibiting the genetic transcription factor that activates TNF-a and IL-1b in synovial tissue (Riehemann K et al., 1999). This proinflammatory transcription factor, known as nuclear factor kappa beta (NF-kb), is known to be elevated in chronic inflammatory diseases and is essential to activation of TNF-a. Nettle is thought to work by preventing degradation of the natural inhibitor of NF-kb in the body. It has also been shown that TNF-a activates NF-kb in synovial cells, leading to the suggestion that a cycle of cross-activation between TNF-a and NF-kb may sustain and amplify the disease process in rheumatoid arthritis (Jue DM et al., 1999).

A study on healthy volunteers showed the anti-inflammatory potential of nettle (Obertreis B, 1998). Lipopolysaccharide was used to stimulate and increase the secretion of proinflammatory cytokines. When nettle extract was given simultaneously in a dose dependent manner, TNF-a and IL-1b concentration was significantly reduced.

Another study conducted on forty patients suffering from acute arthritis compared the effects of 200 mg of a NSAID (diclofenac) with 50 mg of the NSAID in combination with 50 g of stewed nettle leaf per day (Chrubasik S et al., 1997). Total joint scores improved significantly in both groups by approximately 70%. The nettle leaf extract clearly enhanced the anti-inflammatory effect of the NSAID. The addition of nettle extract made possible a 75% dose reduction of the NSAID, while still retaining the same anti-inflammatory effect with reduced side effects.

Ginger
Ginger (Zingiber officinale) is mostly known to us in the West as a spice and a flavor. In China, however, it has been used for thousands of years for medicinal purposes, such as nausea, stomachache, rheumatism and toothache. Modern research has found ginger to be a powerful anti-oxidant and to have strong anti-inflammatory effects.

The pharmacologically active components of the ginger root are thought to be aromatic ketones known as gingerols. These have been shown in experimental studies to inhibit both the cyclooxygenase and lipoxygenase pathways and the production of prostaglandins, thromboxane and leukotrienes (Kiuchi F et al., 1992; Srivastava KC, 1986; Flynn DL et al., 1986), just as the NSAIDs do. No significant side effects have been reported.

Ginger oil is obtained by steam distillation of dried ginger root. In an experimental study on rats (Sharma JN et al., 1997), arthritis was induced in the knee and paw by injection of bacilli, leading to inflammation. One group of rats was also given ginger oil by mouth for 28 days starting the day before the injection. The rats given ginger oil had less than half the knee and paw inflammation compared to the controls.

Glucosamine sulfate
Among the natural therapies for osteoarthritis glucosamine sulfate is probably the best known. It is extensively used as a drug for osteoarthritis in Europe, and it has been readily available in health food stores in the United States in recent years.

Glucosamine is a naturally occurring substance in the body, synthesized in the chondrocytes. In osteoarthritis, this synthesis is defective and insufficient, and supplementation with glucosamine may be useful. The body uses supplemented glucosamine to synthesize the proteoglycans and the water-binding glycosaminoglycans (GAGs) in the cartilage matrix. In addition to providing raw material, the presence of glucosamine seems to stimulate the chondrocytes in their production of these substances. Glucosamine also inhibits certain enzymes, which destroy the cartilage, e.g. collagenase and phospholipase. By blocking pathogenic mechanisms that lead to articular degeneration, glucosamine delays the progression of the disease and relieves symptoms even for weeks after termination of the treatment (Qiu GX et al., 1998).

Osteoarthritis & Rheumatoid Arthritis

There are many studies confirming the excellent effect and safety of glucosamine sulfate. In one well designed study of 178 patients suffering from osteoarthritis of the knee (Qiu GX et al., 1998), one group was treated for 4 weeks with glucosamine sulfate 1500 mg daily and the other group with ibuprofen at 1200 mg per day. Glucosamine relieved the symptoms as effectively as ibuprofen, and was significantly better tolerated than ibuprofen. The safety and tolerability of glucosamine can easily be explained by the fact that it is a physiological substance normally used by the body.

As with most natural remedies the therapeutic effect of glucosamine does not come immediately, and usually takes some weeks to appear (1-8 weeks). Once achieved, it tends to persist for a notable time even after discontinuation of the treatment.

Chondroitin sulfate
Chondroitin sulfate is a major component of cartilage. It is a very large molecule, composed of repeated its of glucosamine sulfate. Like glucosamine, chondroitin sulphate attracts water into the cartilage matrix and stimulates the production of cartilage. Likewise it has the ability to prevent enzymes from dissolving cartilage. Although the absorption of chondroitin sulfate is much lower than that of glucosamine (10-15% versus 90-98%), a few recent studies have shown very good results from long-term treatment with chondroitin sulfate, reducing pain and increasing range of motion.

- A one-year long, double blind clinical study including 42 patients with osteoarthritis showed that chondroitin sulfate was well tolerated and significantly reduced pain and increased joint mobility. The patients were given 800 mg chondroitin sulphate per day or placebo (Uebelhart D et al., 1998).

- In another double-blind study 119 patients with finger-joint osteoarthritis were followed for 3 years. The chondroitin dosage was 400 mg three times daily. X-rays of the finger joints were carried out at the start and at yearly intervals. The number of patients that developed progression of the disease was significantly less in the group treated with chondroitin sulfate (Verbruggen G et al., 1998).

- The improvement in walking time was studied in 80 patients with osteoarthritis in the knee. In this double-blind study the treatment period was 6 months and the chondroitin sulfate dosage 400 mg twice daily. The minimum time to perform a 20 meter walk showed a constant reduction of time only in the chondroitin group. Lower consumption of pain-killing drugs and excellent tolerability was also observed (Bucsi et al., 1998).

Glucosamine alone or in combination with chondroitin sulfate is more and more becoming recognized as the treatment of choice for osteoarthritis even in the United States. Its ability to actually repair and improve joint function in addition to providing pain relief gives it a significant advantage compared to conventional treatment.

Willow bark
Salicylic acid, the basis of aspirin, was first prepared from willow bark by an Italian chemist in 1838. The name of the compound is derived from Salix, the Latin name for the willow genus. Aspirin, or acetylsalicylic acid, is a synthetic form of salicylic acid. Willow bark is rich in salicin and related salicylates that metabolize into salicylic acid. Many plants, such as meadowsweet and wintergreen, also contain these compounds. They have a long tradition of use in Europe, and far fewer side effects than aspirin.

While aspirin/salicin has been shown to have a lowering effect on some of the pro-inflammatory factors, it can also increase ukotriene LTB4, which is a major inflammation promoting mediator. An interesting study (Engstrom K et al., 1997) compared the effect on pro-inflammatory substances of aspirin alone with a combination of low-dose aspirin and fish oil. The results showed that the combination of fish oil and low-dose aspirin has significantly more favorable effects on the pattern of pro-and anti-inflammatory factors than the aspirin alone. LTB4 increased 19% when aspirin was taken by itself, but decreased 69% after intake of aspirin and fish oil together.

Fish oil
It is established that dietary fatty acids determine the composition of lipids in the cell membranes, which influences the production of prostaglandins and leukotrienes that regulate inflammation, a fact that has given rise to interest in the potential of these dietary substances.

Omega-3-oils, such as fish oil (EPA and DHA) and flax seed oil, have the ability to suppress the production of inflammatory mediators and thereby influence the course of chronic inflammatory diseases such as RA. (Kremer JM et al. 1985 and 1992).

A new enteric-coated fish-oil preparation was used in a one-year, double blind study of 78 patients with inflammatory bowel disease. The absorption rate and tolerability was high with this preparation, and after one year 59% of the fish-oil group remained in remission compared to 36% in the placebo group, indicating a significant anti-inflammatory effect (Belluzzi A et al., 1996)

In recent studies, dietary omega-3 oils have shown a suppressive effect on the production of the cytokines IL-1b and TNF-a, which stimulate the production of collagenase and pro-inflammatory prostaglandins (PGE2) (James MJ et al., 1997; Caugey GE et al., 1996). When fish oil supplementation was given to rheumatoid arthritis patients, arachidonic acid levels were reduced by 33% compared to presupplement values (Sperling RI et al., 1987), suggesting that increase of dietary omega-3 oils can be complementary in treating rheumatoid arthritis.

A large number of publications from around the world have confirmed the usefulness of dietary supplementation with omega-3 oils in relieving tender joints and morning stiffness in patients with RA, in some cases eliminating the need for NSAID medication (Kremer JM et al., 1995). Skoldstam et al. (1992) and Lau et al. (1993) found that patients consuming fish oil were able to significantly reduce their NSAID dose compared with a control group.

Of 12 published double blind and placebo-controlled studies with a duration of 12-52 weeks, decreased joint tenderness was the most common favorable outcome reported. Fish oil supplementation significantly decreased the use of NSAIDs in the three studies in which NSAIDs were used. Unlike NSAID use, fish oil consumption is not associated with gastrointestinal toxicity. The results of the studies suggest that the effective dose of fish oil is approximately 3-6 grams per day. Higher dosages did not give better results. There are indications that the combination of EPA and DHA, as it is found in fish oil, has a synergistic effect (Robinson DR et al., 1989).

A study by James MJ et al. (1997) emphasizes the potential for increased efficacy of anti-inflammatory drugs, when using omega-3 oils in the diet. It was observed that diets rich in omega-3 oils and low in omega-6 fats had a drug sparing effect with decreased side effects. Drug toxicity is estimated to contribute 60% of the total cost of treating RA patients in the United States (Prashker MJ et al., 1995). Use of omega3-oils in the diet would appear to offer a simple, safe and inexpensive way to reduce toxicity and side effects from RA medications.

Oxidative damage
Food is not conventionally accepted as influential in the course of inflammatory or degenerative diseases (in contrast to diabetes and vascular heart disease).

We know, however, that oxidative stress or free radical damage is a factor of importance in the development of osteoarthritis, just as it is a major cause of most chronic degenerative diseases as well as aging. There is also strong evidence that oxidative damage occurs in RA patients. Increased oxidation of lipids (peroxidation) as well as depletion of ascorbate in serum and synovial fluid has been observed. High doses of vitamin E, which is a powerful antioxidant, are reported to diminish pain. Most importantly, tumor necrosis factor alpha (TNF-a), which plays a key role in RA, is well-known to cause oxidative stress.

In order to counteract free radical damage, antioxidants are needed. A diet rich in vegetables and fruits is likely to add important antioxidants to the body. This may not always be enough, however. Vitamin C and vitamin E supplements have been studied and found to be important in the treatment of osteoarthritis. Deficient vitamin C intake, which is common with elderly people, impairs the synthesis of collagen, the main protein of cartilage (Bates CJ, 1977). Studies on vitamin E have shown its ability to stimulate the production of cartilage components, such as glycosaminoglycans, as well as to inhibit the breakdown of cartilage.

Healthy food and a minimum of toxins may be more important for our health than we want to believe. The body strives to heal itself, whether it is a cut finger, a cold or a damaged or inflamed joint. It makes sense to find ways to support the body with natural substances that the body can use in the healing process.

Recent research has provided us with new insights into the mechanisms of arthritis, and left us with a scientific understanding of how natural remedies work in harmony with the body rather than against it.

Osteoarthritis & Rheumatoid Arthritis        

Bates CJ: Proline and hydroxyproline excretion and vitamin C status in elderly human subjects. Clin Sci Mol Med (1977) 52: 535-43.

Belluzzi A et al.: Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. NEJM (1996) 334: 1557-1560.

Bertolini DR et al.: Stimulation of bone resorption and inhibition of bone formation in vitro by human tumor necrosis factor. Nature (1986) 319: 516-18.

Birkedal-Hansen H et al.: Matrix metalloproteinases: A review. Crit Rev Oral Biol Med (1993) 4: 197-250.

Bondeson J et al.: Defining therapeutic targets by using adenovirus: Blocking NK-kB inhibits both inflammatory and destructive mechanisms in rheumatoid synovium but spares anti-inflammatory mediators. Proc Natl Acad Sci USA (1999) 96: 5668-5673.

Bourgeois P et al.: Efficacy and tolerability of chondroitin sulfate 1200mg/day vs placebo. Osteoarth Cartil (1998) 6, Suppl. A: 25-30.

Brooks PM et al.: NSAID and osteoarthritis - help or hindrance. J Rheumatol (1982) 9: 3-5.

Bucsi L et al.: Efficacy and tolerability of oral chondroitin sulfate as a slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarth Cartil (1998) 6, Suppl. A: 31-36.

Caugey GE et al.: The effect on human tumor necrosis factor-a and interleukin-1b production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr (1996) 63: 116-22.

Chrubasik S et al.: Evidence for antirheumatic effectiveness of Herba Urticae dioicae in acute arthritis: a pilot study. Phytomedicine (1997) 4: 105-108.

Engstrom K et al.: Effect of Low-dose aspirin in combination with Stable Fish Oil on Eicosanoids. EPA and Eicosanoids. Prost Leukotr Ess Fat Acid (1997) 57: 229.

Feldmann M et al.: Anti-tumor necrosis factor-a therapy of rheumatoid arthritis. Adv Immunol (1997) 84: 283-350.

Feldmann M et al.: Role of cytokines in rheumatoid arthritis. Annu Rev Immunol (1996) 14: 397-440.

Flynn DL et al.: Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds. Prost Leukotr Med (1986) 24: 195-198.

Hardingham T: Chondroitin sulfate and joint disease. Osteoarth Cartil (1998) 6, Suppl. A: 3-5.

Hill PA et al.: The effects of selective inhibitors of matrix metalloproteinases on bone resorption and the identification of MMPs and TIMP-1 in isolated osteoclasts. J Cell Sci (1994) 107: 3055-3064.

James MJ et al.: Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum (1997) 27: 85-97.

Kiuchi F et al.: Inhibition of prostaglandin and leucotriene biosynthesis by gingerols and diarylheptanoids. Chem Pharm Bull (1992) 40: 387-391.

Jue DM et al.: Nuclear factor kb (NF-kb) pathway as a therapeutic target in rheumatoid arthritis. J Kor Med Sci (1999) 14: 231-238.

Kremer JM et al.: Clinical studies of n-3 fatty acids supplementation in patients with rheumatoid arthritis. Rheum Dis Clinics (1992) 17: 391-402.

Kremer JM et al.: Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet (1985) 1(8422): 184-187.

Kremer JM et al.: Fish-oil fatty acid supplementation in active rheumatoid arthritis: a double-blinded, controlled crossover study. Ann Int Med (1987) 106: 497-503.

Needleman P et al.: Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. Proc Natl Acad Sci USA (1979) 76:944-948.

Newman NM et al.: Acetabular bone destruc tion related to non-steroidal anti-inflammatory drugs. Lancet (1985) 2(8445): 11-14.

Obertreis B et al: Ex-vivo in-vitro inhibition of lipopolysaccharide stimulated tumor necrosis factor-a and Interleukin-1b secretion in man whole blood by extractum Urticae dioicae foliorum. Arzneim-Forsch/Drug Res (1996) 46: 389-394.

Paulus HE et al.: Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. Arthr Rheum (1990) 33: 477-484.

Plows D et al.: the role of tumor necrosis factor (TNF) in arthritis: studies in transgenic mice. Rheumatol Eur (1995) Suppl 2: 51-4.

Prashker MJ et al: the total cost of drug therapy for rheumatoid arthritis: a model based on costs of drug, monitoring and xicity. Arthr Rheum (1995) 38: 318-25.

Qiu GX et al.: Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneim-Forsch/Drug Res (1998) 48: 469-474.

Riehemann K et al.: Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kb. FEBS Lett (1999) 442: 89-94.

Robinson DR et al.: Lipid mediators of inflammatory and immune reactions. J Parent Ent Nutr (1988) 12, Suppl. S: S37-S42.

Ronningen H et al: Indomethacin treatment in osteoarthritis of the hip joint. Acta Orthop Scand (1979) 50: 169-74.

Saklatvala J: Tumor necrosis factor-a stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature (1986) 322: 547-49.

Sharma JN et al.: Effects of eugenol and ginger oil on adjuvant arthritis and the kallikreins in rats. Asia Pac J Pharmacol (1997) 12: 9-14.

Sharma JN et al.: Suppressive effects of eugenol and ginger oil on arthritic rats. Pharmacology (1994) 49: 314-318.

Shield MJ: Anti-inflammatory drugs and their effect on cartilage synthesis and renal function. Eur J Rheum Inflam (1993) 13: 7-16.

Skoldstam L et al.: Effects of six months of fish oil supplementation in stable rheumatoid arthritis: A double-blind, controlled udy. Scand J Rheum (1992) 21: 178-185.

Solomon L: Drug induced arthropathy and necrosis of the femoral head. J Bone Joint Surg (1973) 55B: 246-51.

Sperling RI et al.: Effects of dietary supplementation with marine fish oil on leucocyte lipid mediator generation and function in rheumatoid arthritis. Arthr Rheum (1987) 30: 988-997.

Srivastava KC et al: Ginger (Zingiber-officinale) and rheumatic disorders. Med Hypoth (1989) 29: 25-8.

Srivastava KC: Ginger (Zingiber-officinale) in rheumatism and muscular skeletal disorders. Med Hypoth (1992) 39: 342-348.

Uebelhart D et al.: Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarth Cartil ( 98) 6, Supplement A: 39-46.

Verbruggen G et al.: Chondroitin sulphate S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA. Osteoarth Cartil (1998) 6, Suppl. A: 37-38.