In osteoarthritis, the cartilage in joints has become damaged, disrupting the smooth gliding motion of the joint surfaces. The result is pain, swelling, and deformity.
The pain of osteoarthritis typically increases with joint use and improves at rest. For reasons that aren't clear, although x-rays can find evidence of arthritis, the level of pain and stiffness experienced by people does not match the extent of injury noticed on x-rays.
Many theories exist about the causes of osteoarthritis, but we don't really know what causes the disease. Osteoarthritis is often described as "wear and tear" arthritis. However, evidence suggests that this simple explanation is not correct. For example, osteoarthritis frequently develops in many joints at the same time, often symmetrically on both sides of the body, even when there is no reason to believe that equal amounts of wear and tear are present. Another intriguing finding is that osteoarthritis of the knee is commonly (and mysteriously) associated with osteoarthritis of the hand. These factors, as well as others, have led to the suggestion that osteoarthritis may actually be a body-wide disease of the cartilage.
During one's lifetime, cartilage is constantly being turned over by a balance of forces that both break down and rebuild it. One prevailing theory suggests that osteoarthritis may represent a situation in which the degrading forces get out of hand. Some of the proposed natural treatments for osteoarthritis described later may inhibit enzymes that damage cartilage.
When the cartilage damage in osteoarthritis begins, the body responds by building new cartilage. For several years, this compensating effort can keep the joint functioning well. Some of the natural treatments described below appear to work by assisting the body in repairing cartilage. Eventually, however, building forces cannot keep up with destructive ones, and what is called end-stage osteoarthritis develops. This is the familiar picture of pain and impaired joint function.
The conventional medical treatment for osteoarthritis consists mainly of anti-inflammatory drugs, such as naproxen and Celebrex. The main problem with anti-inflammatory drugs is that they can cause ulcers. Another possible problem is that they may actually speed the progression of osteoarthritis by interfering with cartilage repair and promoting cartilage destruction. 1-5 In contrast, two of the treatments described below might actually slow the course of the disease, although this has not been proven.
Several natural treatments for osteoarthritis have a meaningful, though not definitive, body of supporting evidence indicating that they can reduce pain and improve function. In addition, there is some evidence that glucosamine and chondroitin might offer the additional benefit of helping to prevent progressive joint damage.
Inconsistent evidence hints that glucosamine can reduce symptoms of mild to moderate arthritis; a small amount of evidence indicates that regular use can slow down the gradual worsening of arthritis that normally occurs with time.
Glucosamine is widely accepted as a treatment for osteoarthritis. However, the supporting evidence that it works is somewhat inconsistent, with several of the most recent studies failing to find benefit. Two types of studies have been performed: those that compared glucosamine against placebo and those that compared it against standard medications.
In the placebo-controlled category, one of the best trials was a 3-year, double-blind study of 212 people with osteoarthritis of the knee. 21 Participants receiving glucosamine showed reduced symptoms as compared to those receiving placebo.
Benefits were also seen in other double-blind, placebo-controlled studies, enrolling a total of more than 800 people and ranging in length from 4 weeks to 3 years. 10,14,101,103,104,138, 182
Other double-blind studies enrolling a total of more than 400 people compared glucosamine against ibuprofen and found glucosamine equally effective as the drug. 11,16,18
However, most recent studies have not shown benefit. In four studies involving a total of almost 500 people, use of glucosamine failed to improve symptoms to any greater extent than placebo. 19,20,99,139 And the list goes on. A study involving 222 participants with hip osteoarthritis, 2 years of treatment with glucosamine was no better than placebo at improving pain or function. 196 Another study involving 147 women with osteoarthritis found glucosamine to be no more effective than home exercises over an 18-month period. 198 A third study evaluated the effects of stopping glucosamine after taking it for 6 months. In this double-blind trial of 137 people with osteoarthritis of the knee, participants who stopped using glucosamine (and, unbeknownst to them, took placebo instead) did no worse than people who stayed on glucosamine. 140 In a fourth, very large (1,583-participant) study neither glucosamine (as glucosamine hydrochloride) nor glucosamine plus chondroitin was more effective than placebo. 152 Another study also failed to find benefit with glucosamine plus chondroitin. 187 And finally, in a systematic review including10 randomized trials involving 3,803 patients with osteoarthritis of hip or knee,researchers found that glucosamine alone, chondroitin alone, or the combination of glucosamine and chondroitin did not improve pain. 202
It appears that most of the positive studies were funded by manufacturers of glucosamine products, and most of the studies performed by neutral researchers failed to find benefit. 188
Many popular glucosamine products combine this supplement with methylsulfonylmethane (MSM). One study published in India reported that both MSM and glucosamine improve arthritis symptoms as compared to placebo, but that the combination of MSM and glucosamine was even more effective than either supplement separately. 138 However, India has not yet achieved a reputation for conducting reliable medical trials.
Two studies reported that glucosamine can slow the progression of osteoarthritis. However, as with the positive studies of glucosamine for reducing symptoms, both of these studies were funded by a major glucosamine manufacturer.
A 3-year, double-blind, placebo-controlled study of 212 individuals found indications that glucosamine may protect joints from further damage. 21 Over the course of the study, individuals given glucosamine showed some actual improvement in pain and mobility, while those given placebo worsened steadily. Furthermore, x-rays showed that glucosamine treatment prevented progressive damage to the knee joint.
A separate 3-year study enrolling 202 people found similar results. 101
Furthermore, a follow-up analysis 5 years after the conclusion of the above two studies found suggestive evidence that use of glucosamine reduced the need for knee replacement surgery. 190
However, the aforementioned study involving 222 patients with osteoarthritis of the hip failed to show any significant change on x-ray findings following 2 years of glucosamine treatment compared to placebo. 196
Glucosamine appears to stimulate cartilage cells in the joints to make proteoglycans and collagen, two proteins essential for the proper function of joints. 6-10 Glucosamine may also help prevent collagen from breaking down. 33
For more information, including dosage and safety issues, see the full Glucosamine article.
As described in the previous section, the supplement chondroitin is often combined with glucosamine. Several studies have evaluated chondroitin used alone, as well, with some positive results, both for improving symptoms and slowing the progression of the disease. On balance, however, the evidence for chondroitin’s effectiveness for osteoroarthritis remains inconsistent. 197
According to some but not all double-blind, placebo-controlled studies chondroitin may relieve symptoms of osteoarthritis.
One study enrolled 85 people with osteoarthritis of the knee and followed them for 6 months. 34 Participants received either 400 mg of chondroitin sulfate twice daily or placebo. At the end of the trial, doctors rated the improvement as good or very good in 69% of those taking chondroitin sulfate but in only 32% of those taking placebo.
Another way of comparing the results is to look at maximum walking speed among participants. Whereas individuals in the chondroitin group were able to improve their walking speed gradually over the course of the trial, walking speed did not improve at all in the placebo group. Additionally, there were improvements in other measures of osteoarthritis, such as pain level, with benefits seen as early as 1 month. This suggests that chondroitin was able to stop the arthritis from gradually getting worse.
Good results were seen in a 12-month, double-blind trial that compared chondroitin against placebo in 104 individuals with arthritis of the knee, 35 as well as in a 12-month trial of 42 participants. 36
Another interesting study evaluated intermittent or “on and off” use of chondroitin. 121 In this study, 120 people received either placebo or 800 mg of chondroitin sulfate daily for two separate 3-month periods over a year. The results showed that even when taken this way, use of chondroitin improved symptoms.
Benefits were also seen in two short-term trials involving a total of about 240 individuals. 37,38
Generally positive results were also seen in other studies, including one that found chondroitin about as effective as the anti-inflammatory drug diclofenac. 40-42
However, a very large (1,583-participants) and well-designed study failed to find either chondroitin or glucosamine plus chondroitin more effective than placebo. 153 When this study is pooled together with the two other best designed trials, no overall benefit is seen. 185 Yet another study also failed to find benefit with glucosamine plus chondroitin. 187 It has been suggested that chondroitin, like glucosamine, may primarily show benefit in studies funded by manufacturers of chondroitin products.
Some evidence suggests that, like glucosamine, chondroitin might slow the progression of arthritis.
An important feature of the study of 42 individuals mentioned previously was that the individuals taking a placebo showed progressive joint damage over the year, but among those taking chondroitin sulfate no worsening of the joints was seen. 43 In other words, chondroitin sulfate seemed to protect the joints of osteoarthritis sufferers from further damage.
A longer and larger double-blind, placebo-controlled trial also found evidence that chondroitin sulfate can slow the progression of osteoarthritis. 44 One hundred and nineteen people were enrolled in this study, which lasted a full 3 years. Thirty-four of the participants received 1,200 mg of chondroitin sulfate per day; the rest received placebo. Over the course of the study researchers took x-rays to determine how many joints had progressed to a severe stage.
During the 3 years of the study, only 8.8% of those who took chondroitin sulfate developed severely damaged joints, whereas almost 30% of those who took placebo progressed to this extent.
Similar long-term benefits were seen in two other studies, enrolling a total of more than 200 people. 45,122
Additional evidence comes from animal studies. Researchers measured the effects of chondroitin sulfate (administered both orally and via injection directly into the muscle) in rabbits, in which cartilage damage had been induced in one knee by the injection of an enzyme. 46 After 84 days of treatment, the damaged knees in the animals that had been given chondroitin sulfate had significantly more cartilage left than the knees of the untreated animals. Taking chondroitin sulfate by mouth was as effective as taking it through an injection.
Looking at the sum of the evidence, it does appear that chondroitin sulfate may actually protect joints from damage in osteoarthritis. However, the scientific record suffers from a paucity of truly independent researchers.
For more information, including dosage and safety issues, see the full Chondroitin article.
A substantial body of scientific evidence indicates that S-adenosylmethionine (SAMe) can relieve symptoms of arthritis. 50,203 Numerous double-blind studies involving more than a thousand participants in total suggest that it is approximately as effective for this purpose as standard anti-inflammatory drugs.
One of the best double-blind studies enrolled 732 patients and followed them for 4 weeks. 205 Over this period, 235 of the participants received 1,200 mg of SAMe per day, while a similar number took either placebo or 750 mg daily of the standard drug naproxen. The majority of these patients had experienced moderate symptoms of osteoarthritis of either the knee or of the hip for an average of 6 years.
The results indicate that SAMe provided as much pain-relieving effect as naproxen and that both treatments were significantly better than placebo. However, differences did exist between the two treatments. Naproxen worked more quickly, producing readily apparent benefits at the 2-week follow-up, whereas the full effect of SAMe was not apparent until 4 weeks. By the end of the study, both treatments were producing the same level of benefit.
In a double-blind study that compared SAMe against the new anti-inflammatory drug Celebrex (celecoxib), once more, the drug worked faster than the supplement, but in time both were providing equal benefits. 123
Evidence regarding slowing the progression of arthritis is, at present, limited to studies involving animals rather than people. 52,53
For more information, including dosage and safety issues, see the full SAMe article.
Special extracts of avocado and soybeans called avocado/soybean unsaponifiables (ASUs) have been investigated as a treatment for osteoarthritis with very promising results in studies enrolling a total of several hundred people. 85-92,125
For example, in a double-blind trial, 260 individuals with arthritis of the knee were given either placebo or ASU at 300 or 600 mg daily. 93 The results over 3 months showed that use of ASU significantly improved arthritis symptoms as compared to placebo. There was no significant difference seen between the two doses tested.
ASU was evaluated in a review of randomized trials. ASU was associated with significant pain reduction (300 and 600 mg) and improved function (300 mg). There were no differences found with ASU (300 mg) use after 1 year. 211
Thus far, however, it does not appear that ASU can slow the progression of osteoarthritis. 126
A type of naturally occurring fatty acid called cetylated fatty acids have shown growing promise for osteoarthritis. It is used both as a topical cream and as an oral supplement.
Three double-blind placebo-controlled studies have found cetylated fatty acids helpful for osteoarthritis . Two involved a topical product, and one used an oral formulation.
In one of the studies using the cream, 40 people with osteoarthritis of the knee applied either cetylated fatty acid or placebo to the affected joint. 128 The results over 30 days showed greater improvements in range of motion and functional ability among people using the real cream than those using the placebo cream. In another 30-day study, also enrolling 40 people with knee arthritis, use of cetylated fatty acid cream improved postural stability, presumably due to decreased pain levels. 145 In addition, a 68-day, double-blind, placebo-controlled study of 64 people with knee arthritis tested an oral cetylated fatty acid supplement (the supplement also contained lesser amounts of lecithin and fish oil .) 147 Participants in the treatment group experienced improvements in swelling, mobility and pain level as compared to those in the placebo group. Inexplicably, the study report does not discuss whether or not side effects occurred. While this is a promising body of research, it is far from definitive. Current advertising claims for cetylated fatty acids go far beyond the existing evidence. For example, a number of websites claim that cetylated fatty acids are more effective than glucosamine or chondroitin . However, no comparison studies have been performed upon which such a claim could be rationally based.
For more information, including dosage and safety issues, see the full Cetylated Fatty Acid article.
Acupuncture has shown inconsistent benefit as a treatment for osteoarthritis. 72,102,108,109,148,154,169,171,179,191,192,200,206
A 2006 meta-analysis (systematic statistical review) of studies on acupuncture for osteoarthritis found 8 trials that were similar enough to be considered together. 192 A total of 2,362 people were enrolled in these studies. The authors of the meta-analysis concluded that acupuncture should be regarded as an effective treatment for osteoarthritis.
However, as it happens, one study comprised almost half of all the people considered in this meta-analysis, and it failed to find real acupuncture more effective than sham acupuncture. In this study, published in 2006, 1,007 people with knee osteoarthritis were given either real acupuncture, fake acupuncture, or standard therapy over 6 weeks. 169 Though both real acupuncture and fake acupuncture were more effective than no acupuncture, there was no significant difference in benefits between the two acupuncture groups. In general, larger studies are more reliable than small ones. For this reason, it is always somewhat questionable when meta-analysis combines one very large negative study and a number of smaller positive ones to come up with a positive outcome.
Another review, published in 2007, nuanced its conclusions differently. 189 It concluded that real acupuncture produces distinct benefits in osteoarthritis as compared to no treatment, but that fake acupuncture is very effective for osteoarthritis too. When comparing real acupuncture to fake acupuncture, the difference in outcome—while it might possibly be statistically significant—is so trivial as to make no difference in real life. In other words, virtually all of the benefit of acupuncture for osteoarthritis is a placebo effect.
A similar effect was found in another review of 11 randomized trials. Acupuncture decreased pain in people with osteoarthritis pain compared to those who had sham acupuncture or no treatment. Follow-up ranged from 1-12 months. 207
Slight statistical difference between real and fake acupuncture could easily have been due to problems of single-blind studies. Acupuncturists who know they are performing real acupuncture may subconsciously convey more confidence to their patients than those who know they are performing fake acupuncture. The history of medical studies makes it clear that such unconscious communications can greatly affect results; since, in fact, the evidence shows only a minute difference between the results of real and fake acupuncture, it is quite possible that this transmission of confidence (or lack of it) is the entire cause of the difference, and that the specific techniques and theories of acupuncture themselves play no role at all.
This may explain why a reliable randomized trial with 252 people found that acupuncture (needle and laser) did not improve knee pain or function when compared to sham acupuncture. When acupuncture was compared to no treatment, it demonstrated statistical improvement, but the clinical effects were minimal for the person being treated.212
For more information, see the full Acupuncture article.
A 6-week, double-blind, placebo-controlled study of 247 individuals with osteoarthritis of the knee evaluated a combination herbal product containing ginger and the Asian spice galanga ( Alpinia galanga ). 94 The results showed that participants in the ginger/galanga group improved to a significantly greater extent than those receiving placebo. However, despite news reports claiming that this study proves ginger effective for osteoarthritis, it only provides information on the effectiveness of the herbal combination. The two double-blind studies performed on ginger alone were small and produced contradictory results. 95,127 Furthermore, another study found that massage combined with the topical application of essential oils made from ginger and orange was no better than massage plus olive oil in patients with osteoarthritis of the knee. 199
The herb white willow contains the aspirin-like substance salicin. A 2-week, double-blind, placebo-controlled trial of 78 individuals with arthritis found evidence that willow extracts can relieve osteoarthritis pain. 69 However, another double-blind study enrolling 127 people with osteoarthritis found white willow less effective than a standard anti-inflammatory drug and no more effective than placebo. 142 Again, the likely explanation for these contradictory results is that white willow at usual doses provides relatively modest benefits.
As noted above, the supplement methyl sulfonyl methane (MSM) has shown promise for osteoarthritis when taken along with glucosamine. 138 Besides that study, benefits were also seen in a 12-week, double-blind, placebo-controlled trial of 50 people with osteoarthritis, utilizing MSM at a dose of 3 g twice daily. 155 However, in a comprehensive review of 6 studies involving 681 patients with osteoarthritis of knee, researchers concluded it is not yet possible to convincingly determine whether or not either DSMO or MSM is beneficial. 197
A randomized trial with 200 patients found collagen hydrolysate significantly reduced joint pain when compared to placebo. Patients, who were followed for 6 months, were over 50 years old with hip, knee, elbow, shoulder or lumbar spine pain. 208
Other treatments with incomplete supporting evidence from double-blind trials include Ayurvedic herbal combination therapy , 81,174cat’s claw , 100 a proprietary complex of minerals with or without cat's claw, 156devil's claw , 65,66,157-158proteolytic enzymes , 97,98,159,160rose hips , 143,161-162,188soy protein, 150 and vitamin B 3 . 64
Traditional Chinese herbal medicine has also shown some promise for osteoarthritis. However, one study that compared a commonly used Chinese herbal product (Duhuo Jisheng Wan) to the drug diclofenac found that the herb worked more slowly than the drug, yet produced about an equal rate of side effects.
In a randomized trial, GCSB-5 (a combination of 6 dried herbs) was as safe and effective as a prescription nonsteroidal anti-inflammatory drug (celecoxib) in treating knee osteoarthritis. 210
Growing but definitive evidence suggests that the natural substance hyaluronic acid may help reduce osteoarthritis symptoms when it is injected directly into an affected joint. 163-166,173,195 However, there is absolutely no reason to believe that oral hyaluronic acid should help, and one study failed to show any significant benefit. 194
Incomplete and inconsistent evidence from human and animal studies only weakly suggests that green-lipped mussel might alleviate osteoarthritis symptoms. 82-84,130-136,167 A badly designed human study hints that krill oil might be helpful as well. 184
Numerous other herbs and supplements sometimes recommended for osteoarthritis include: beta-carotene , boron , cartilage , chamomile , copper , dandelion , D-phenylalanine , feverfew , molybdenum , selenium , turmeric , and yucca . However, there is little to no evidence as yet that these treatments are effective.
Other studies provide limited evidence that certain supplements proposed for osteoarthritis do not work. For example, a 2-year, double-blind study of 136 people with knee arthritis found vitamin E ineffective for either reducing symptoms or slowing the progression of the disease. 118 In addition, a 6-month, double-blind, placebo-controlled trial of 77 people with osteoarthritis failed to find any symptomatic benefit with vitamin E. 96 Similarly, in a large (almost 400-participant) 5-year, double-blind, placebo-controlled study, use of injected mesoglycan failed to slow the progression of osteoarthritis. 119 A fairly small study failed to find the enzyme bromelain helpful for reducing symptoms. 175
Prolotherapy is a special form of injection therapy that is popular among some alternative practitioners. A double-blind, placebo-controlled study evaluated the effects of 3 prolotherapy injections (using a 10% dextrose solution) at 2-month intervals in 68 people with osteoarthritis of the knee. 110 At 6-month follow-up, participants who had received prolotherapy showed significant improvements in pain at rest and while walking, reduction in swelling, episodes of "buckling," and range of flexion, as compared to those who had received placebo treatment. The same research group performed a similar double-blind trial of 27 individuals with osteoarthritis in the hands. 111 The results at 6-month follow-up showed that range of motion and pain with movement improved significantly in the treated group as compared to the placebo group.
Several double-blind, placebo-controlled studies suggest that pulsed electromagnetic field therapy, a special form of magnet therapy , can improve symptoms of osteoarthritis. 112-115 One small study provides extremely weak supporting evidence for the more ordinary form of magnet therapy: static magnets. 124 A subsequent much larger study of static magnets failed to find real magnets more effective than placebo magnets, but a manufacturing error may have obscured genuine benefits (some people in the placebo group were accidentally given active magnets). 149 In yet another placebo-controlled trial, the use of a magnetic knee wrap for 12 weeks was associated with a significant increase in quadriceps (thigh muscle) strength in patients with knee osteoarthritis. 201
Limited evidence supports the use of bee venom injections for osteoarthritis. 168 Hot water therapy ( balneotherapy ), 176-180, 186relaxation therapies , 172 and various forms of exercise , including hatha yoga and tai chi , have also all shown some promise. 117,173,183,193 However, for none of these therapies is the supporting evidence convincing.
In a 2011 review of the literature, researchers analyzed 4 studies investigating the benefits of manual therapy (including massage therapy, joint mobilization, and manipulation ) for osteoarthritis of the hip or knee. 204 The results were inconclusive. Although one of the studies (involving 68 people) did find that massage therapy helped to improve pain and function, it was compared to no intervention rather than another treatment or a placebo.
Oligomeric proanthocyanidins (OPCs) are chemicals derived from pine bark extract. Three trials, which were part of a larger systematic review, hinted at the possible effectiveness of OPCs in treating osteoarthritis of the knee. 205
Leech saliva has anesthetizing, anti-inflammatory, and vasodilating properties. In a randomized crossover trial of 52 patients with knee osteoarthritis, one application of leech therapy was associated with improvements in pain, function and overall symptoms compared to one-time transcutaneous electrical nerve stimulation. Patients switched therapies after 42 days and were followed for an additional 21 days after the second treatment. Only about three-quarters of the patients completed the study. 209
For a discussion of homeopathic approaches to osteoarthritis, see the Homeopathy Database .
Various herbs and supplements may interact adversely with drugs used to treat osteoarthritis. For more information on this potential risk, see the individual drug article in the Drug Interactions section of this database.
15. Rovati LC. A large, randomized, placebo controlled, double-blind study of glucosamine sulfate vs. piroxicam and vs. their association, on the kinetics of the symptomatic effect in knee osteoarthritis. Osteoarthritis Cartilage. 1994;2(suppl 1):56.
18. Thie NM, Prasad NG, Major PW. Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial. J Rheumatol. 2001;28:1347-1355.
22. Das A Jr, Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage. 2000;8:343-350.
34. Bucsi L, Poor G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage. 1998;6(suppl A):31-36.
37. Bourgeois P, Chales G, Dehais J, et al. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo. Osteoarthritis Cartilage. 1998;6(suppl A):25-30.
38. Mazieres B, Loyau G, Menkes CJ, et al. Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo [in French; English abstract]. Rev Rhum Mal Osteoartic. 1992;59:466-472.
39. Das A Jr, Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage. 2000;8:343-350.
40. L'Hirondel JL. Double-blind clinical study with oral administration of chondroitin sulphate versus placebo in tibiofemoral gonarthrosis (125 patients) [in German]. Litera Rheumatol. 1992;14:77-84.
41. Morreale P, Manopulo R, Galati M, et al. Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol. 1996;23:1385-1391.
42. Mazieres B, Combe B, Phan Van A, et al. Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study. J Rheumatol. 2001;28:173-181.
44. Verbruggen G, Goemaere S, Veys EM. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA. Osteoarthritis Cartilage. 1998;6(suppl A):37-38.
46. Uebelhart D, Thonar EJ, Zhang J, et al. Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. Osteoarthritis Cartilage. 1998;6(suppl A):6-13.
52. Kalbhen DA, Jansen G. Pharmacological studies on the antidegenerative effect of ademetionine in experimental osteoarthritis [in German; English abstract]. Arzneimittelforschung. 1990;40:1017-1021.
53. Barcelo HA, Wiemeyer JC, Sagasta CL, et al. Experimental osteoarthritis and its course when treated with S-adenosyl-L-methionine (SAMe) [in Spanish; English abstract]. Rev Clin Esp. 1990;187:74-78.
66. Leblan D, Chantre P, Fournie B. Harpagophytum procumbens in the treatment of knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-blind trial versus diacerhein. Joint Bone Spine. 2000;67:462-467.
69. Schmid B, Ludtke R, Selbmann HK, et al. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized, placebo-controlled, double blind clinical trial [translated from German]. Z Rheumatol. 2000;59:314-320.
72. Fink MG, Kunsebeck HW, Wippermann B. Effect of needle acupuncture on pain perception and functional impairment of patients with coxarthrosis [in German; English abstract]. Z Rheumatol. 2000;59:191-199.
85. Appelboom T, Schuermans J, Verbruggen G, et al. Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis. A double blind, prospective, placebo-controlled study. Scand J Rheumatol. 2001;30:242-247.
86. Mauviel A, Daireaux M, Hartmann DJ, et al. Effects of unsaponifiable extracts of avocado/soy beans (PIAS) on the production of collagen by cultures of synoviocytes, articular chondrocytes and skin fibroblasts [in French]. Rev Rhum Mal Osteoartic. 1989;56:207-211.
87. Mauviel A, Loyau G, Pujol JP. Effect of unsaponifiable extracts of avocado and soybean (Piascledine) on the collagenolytic action of cultures of human rheumatoid synoviocytes and rabbit articular chondrocytes treated with interleukin-1 [in French; English abstract]. Rev Rhum Mal Osteoartic. 1991;58:241-245.
88. Mazieres B, Tempesta C, Tiechard M, et al. Pathologic and biochemical effects of a lipidic avocado and soya extract on an experimental post-contusive model of OA [abstract]. Osteoarthritis Cartilage. 1993;1:46.
89. Boumediene K, Felisaz N, Bogdanowicz P, et al. Avocado/soya unsaponifiables enhance the expression of transforming growth factor beta1 and beta2 in cultured articular chondrocytes. Arthritis Rheum. 1999;42:148-156.
90. Henrotin YE, Labasse AH, Jaspar JM, et al. Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 production by human articular chondrocytes. Clin Rheumatol. 1998;17:31-39.
91. Maheu E, Mazieres B, Valat JP, et al. Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month followup demonstrating a persistent effect. Arthritis Rheum. 1998;41:81-91.
92. Blotman F, Maheu E, Wulwik A, et al. Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip: a prospective, multicenter, three-month, randomized, double-blind, placebo-controlled trial. Rev Rhum Engl Ed. 1997;64:825-834.
93. Appelboom T, Schuermans J, Verbruggen G, et al. Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis. A double blind, prospective, placebo-controlled study. Scand J Rheumatol. 2001;30:242-247.
96. Brand C, Snaddon J, Bailey M, et al. Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study. Ann Rheum Dis. 2001;60:946-949.
100. Piscoya J, Rodriguez Z, Bustamante SA, et al. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis . Inflamm Res. 2001;50:442-448.
101. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2002;162:2113-2213.
105. Nguyen P, Mohamed SE, Gardiner D, et al. A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study. Cranio. 2001;19:130-139.
106. Cohen M, Wolfe R, Mai T, et al. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol. 2003;30:523-528.
110. Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000;6:68-70,72-74,77-80.
111. Reeves KD, Hassanein K. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. J Altern Complement Med. 2000;6:311-320.
113. Trock DH, Bollet AJ, Markoll R. The effect of pulsed electromagnetic fields in the treatment of osteoarthritis of the knee and cervical spine. Report of randomized, double blind, placebo controlled trials. J Rheumatol. 1994;21:1903-1911.
114. Jacobson JI, Gorman R, Yamanashi WS, et al. Low-amplitude, extremely low frequency magnetic fields for the treatment of osteoarthritic knees: a double-blind clinical study. Altern Ther Health Med. 2001;7:54-60,62-64,66-69.
116. Jung YB, Roh KJ, Jung JA, et al. Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study. Am J Chin Med. 2001;29:485-491.
118. Wluka AE, Stuckey S, Brand C, et al. Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. J Rheumatol. 2002;29:2585-2591.
119. Pavelka K, Gatterova J, Gollerova V, et al. A 5-year randomized controlled, double-blind study of glycosaminoglycan polysulphuric acid complex (Rumalon®) as a structure modifying therapy in osteoarthritis of the hip and knee. Osteoarthritis Cartilage. 2000;8:335-342
121. Uebelhart D, Malaise M, Marcolongo R et al. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage. 2004;12:269-276.
122. Uebelhart D, Malaise M, Marcolongo R et al. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage. 2004;12:269-276.
123. Najm WI, Reinsch S, Hoehler F, et al. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. BMC Musculoskelet Disord. 2004;5:6.
124. Wolsko PM, Eisenberg DM, Simon LS et al. Double-blind placebo-controlled trial of static magnets for the treatment of osteoarthritis of the knee: results of a pilot study. Altern Ther Health Med. 2004;10:36-43.
128. Kraemer WJ, Ratamess NA, Anderson JM et al. Effect of a cetylated fatty acid topical cream on functional mobility and quality of life of patients with osteoarthritis. J Rheumatol. 2004;31:767-74.
130. Cho SH, Jung YB, Seong SC, et al. Clinical efficacy and safety of Lyprinol, a patented extract from New Zealand green-lipped mussel ( Perna canaliculus ) in patients with osteoarthritis of the hip and knee: a multicenter 2-month clinical trial. Allerg Immunol (Paris). 2003;35:212-216.
138. Usha P.R., Naidu M.U.R. Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clinical Drug Investigation. 2004;24:353-363.
139. McAlindon T, Formica M, LaValley M, et al. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med. 2004;117:643-649.
141. Bjordal JM, Ljunggren AE, Klovning A, et al. Nonsteroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. BMJ. 2004 Nov 23. [Epub ahead of print]
142. Biegert C, Wagner I, Ludtke R, et al. Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2 randomized double-blind controlled trials. J Rheumatol. 2004;31:2121-2130.
143. Rein E, Kharazmi A, Winther K, et al. A herbal remedy, Hyben Vital (stand. powder of a subspecies of Rosacanina fruits), reduces pain and improves general wellbeing in patients with osteoarthritis—a double-blind, placebo-controlled, randomised trial. Phytomedicine. 2004;11:383-391.
145. Kraemer WJ, Ratamess NA, Maresh CM et al. Effects of treatment with a cetylated fatty acid topical cream on static postural stability and plantar pressure distribution in patients with knee osteoarthritis. J Strength Cond Res. 2005;19:115-121.
146. Kraemer, WJ, et al. One week of treatment with a cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in patients with arthritis of the knee, elbow, and wrist. J Strength and Cond Res. 2005;19: in press.
151. Teekachunhatean S, Kunanusorn P, Rojanasthien N, et al. Chinese herbal recipe versus diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial [ISRCTN70292892]. BMC Complement Altern Med. 2004 Dec 13. [Epub ahead of print].
155. Kim LS, Axelrod LJ, Howard P, et al. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2005 Nov 22. [Epub ahead of print]
156. Miller MJ, Mehta K, Kunte S et al. Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711]. J Inflamm (Lond). 2005 Oct 21. [Epub ahead of print]
157. Leblan D, Chantre P, Fournie B. Harpagophytum procumbens in the treatment of knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-blind trial versus diacerhein. Joint Bone Spine. 2000;67:462-467.
159. Akhtar NM, Naseer R, Farooqi AZ, et al. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee--a double-blind prospective randomized study. Clin Rheumatol. 2004;23:410-415.
160. Klein G, Kullich W, Schnitker J, et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006;24:25-30.
162. Winther K, Apel K, Thamsborg G, et al. A powder made from seeds and shells of a rose-hip subspecies (Rosa canina) reduces symptoms of knee and hip osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial. Scand J Rheumatol. 2005;34:302-308.
164. Petrella RJ, Petrella M. A prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intraarticular hyaluronic Acid for osteoarthritis of the knee. J Rheumatol. 2006;33:951-956.
166. Salk RS, Chang TJ, D'Costa WF, et al. Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized, double-blind pilot study. J Bone Joint Surg Am. 2006;88:295-302.
167. Cobb CS, Ernst E. Systematic review of a marine nutriceutical supplement in clinical trials for arthritis: the effectiveness of the New Zealand green-lipped mussel Perna canaliculus. Clin Rheumatol. 2005 Oct 12. [Epub ahead of print].
173. Fernandez Lopez JC, Ruano-Ravina A. Efficacy and safety of intraarticular hyaluronic acid in the treatment of hip osteoarthritis: a systematic review. Osteoarthritis Cartilage. 2006 Sep 14. [Epub ahead of print]
174. Chopra A, Lavin P, Patwardhan B, et al. A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an ayurvedic drug, on osteoarthritis of the knees. J Clin Rheumatol. 2006;10:236-245.
178. Fioravanti A, Valenti M, Altobelli E, et al. Clinical efficacy and cost-effectiveness evidence of spa therapy in osteoarthritis. The results of "Naiade" Italian Project. Panminerva Med. 2003;45:211-217.
181. Grube B, Grunwald J, Krug L, et al. Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: Results of a double-blind, randomised, bicenter, placebo-controlled trial. Phytomedicine. 2006 Dec 12. [Epub ahead of print]
182. Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007 Jan 30. [Epub ahead of print].
186. Karagulle M, Karagulle MZ, Karagulle O, et al. A 10-day course of SPA therapy is beneficial for people with severe knee osteoarthritis: a 24-week randomised, controlled pilot study. Clin Rheumatol. 2007 Apr 13. [Epub ahead of print]
187. Messier SP, Mihalko S, Loeser RF, et al. Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthritis Cartilage. 2007 Jun 8. [Epub ahead of print]
190. Bruyere O, Pavelka K, Rovati LC, et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteoarthritis Cartilage. 2007 Jul 26. [Epub ahead of print]
191. Foster NE, Thomas E, Barlas P, et al. Acupuncture as an adjunct to exercise based physiotherapy for osteoarthritis of the knee: randomised controlled trial. BMJ. 2007 Aug 15. [Epub ahead of print]
194. Kalman DS, Heimer M, Valdeon A, et al. Effect of a natural extract of chicken combs with a high content of hyaluronic acid (Hyal-Joint®) on pain relief and quality of life in subjects with knee osteoarthritis: a pilot randomized double-blind placebo-controlled trial. Nutr J. 2008 Jan 21.
197. Brien S, Prescott P, Bashir N, et al. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Osteoarthritis Cartilage. 2008 Apr 14.
198. Kawasaki T, Kurosawa H, Ikeda H, et al. Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial. J Bone Miner Metab. 2008;26:279-287.
199. Yip YB, Tam AC. An experimental study on the effectiveness of massage with aromatic ginger and orange essential oil for moderate-to-severe knee pain among the elderly in Hong Kong. Complement Ther Med. 2008;16:131-138.
200. Jubb R, Tukmachi E, Jones P, et al. A blinded randomised trial of acupuncture (manual and electroacupuncture) compared with a non-penetrating sham for the symptoms of osteoarthritis of the knee. Acupunct Med. 2008;26:69-78.
203. De Silva V, El-Metwally A, Ernst E, Lewith G, Macfarlane GJ. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology. 2010 Dec 17.
206. White P, Bishop FL, Prescott P, Scott C, Little P, Lewith G. Practice, practitioner, or placebo? A multifactorial, mixed-methods randomized controlled trial of acupuncture. Pain. 2012;153(2):455-462.
210. Park YG, Ha CW, et al. A prospective, randomized, double-blind, multicenter comparative study on the safety and efficacy of Celecoxib and GCSB-5, dried extracts of six herbs, for the treatment of osteoarthritis of knee joint. J Ethnopharmacol. 2013;149(3):816-824.
Last reviewed September 2014 by EBSCO CAM Review Board
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