Osteoarthritis and the Ideal Treatment 

Stephanie Jacks

     Osteoarthritis, or degenerative joint disease, is a form of arthritis characterized by the breakdown of cartilage within joints.  Cartilage serves to provide cushion at the ends of bones, and when the cushion is not sufficient, as in osteoarthritis, the bones rub together.  As a result, osteoarthritis sufferers are constantly plagued by stiff, swollen, and inflamed joints (http://www.arthritis.org/answers/diseasecenter/oa.asp).  It is a relatively common condition, with an estimated 20 million American sufferers, most of whom are elderly (http://webmd.lycos.com/content/article/1668.50297).  Traditional treatments include Tylenol, aspirin, or other non-steroidal anti-inflammatory drugs (NSAIDs), but the long-term negative effects of these drugs combined with the fact that they offer only short-term relief has led doctors and scientists to search for better treatment options.  While nutritional supplements as a form of alternative medicine have been slow to gain acceptance by American physicians (Schenck, 2000), glucosamine has surfaced as a consistently effective treatment method for osteoarthritis, and when used in conjunction with chondroitin, the relief this treatment program can provide for sufferers of this debilitating condition is long-awaited and much-welcomed.

What is glucosamine?
How does it work?
How effective is the treatment?
How does the glucosamine treatment compare to traditional methods of treatment?
What evidence is offered in support of these claims?
What’s the downside?
Scientific Analysis of Data

What is glucosamine?
     Glucosamine is a natural sugar produced by the body and found in some foods (http://webmd.lycos.com/content/article/1677.57489).  It is involved in the production, maintenance, and repair of cartilage, a rubber-like padding that covers the ends of bones.  Glucosamine can be synthesized for commercial use from crab, lobster, or shrimp shells (Ghosh, Smith, and Wells, 1992).  Those with allergies to shellfish need not worry, because the allergy is to the meat, not the shell (http://webmd.lycos.com/content/article/1707.50223).  In the making of the supplemental tablets, glucosamine is combined with sulfate or hydrochloride.  The recommended dosage is usually between 1000 and 2000 milligrams a day, and glucosamine is often taken in conjunction with chondroitin, which is shown to enhance treatment results. (http://webmd.lycos.com/content/article/1677.57489).
How does it work? 
     Glucosamine stimulates production of glycosaminoglycans and proteoglycans, the two essential building blocks of cartilage.  Advocates of the treatment say that artificially synthesized glucosamine supplements can jumpstart glucosamine production within joints.  Choindroitin is made of many of the same molecules as glucosamine, and essentially serves the same purpose.  The long-lasting pain relief and functional improvements that are reported by users of the supplement come as a result of anti-inflammatory agents, an increase in cartilage building activities, and a reduction in the enzymatic destruction of cartilage.  Along with a termination in the progression of joint damage, reversal of damage is also highly likely.  The rapid pain relief upon initiation of a glucosamine supplement treatment program is a result of increased production of hyaluronic acid, which is involved in lubrication and shock-absorption activities within joint fluids.  Osteoarthritis is characterized by a dramatic deficit in hyaluronic acid, leading to the typical complaints of pain and stiffness by arthritis sufferers.  After taking glucosamine supplements for 10 days at 800 milligrams a day, an increase in hyaluronic acid can be detected.   Those seeking an even faster method of relief may wish to consider direct injections into the afflicted joint.  (http://www.drmcdougall.com/Newsletter/sept_oct99.1.htm)

How effective is the glucosamine-chondroitin treatment?
    While glucosamine has been used by veterinarians for many years to treat arthritis in dogs and horses, it has only recently gained prominence as an effective treatment for human osteoarthritis in the United States.  Even though it has been widely prescribed in Europe since the 1980s, physicians in the United States have been very slow to accept this method of treatment.  The glucosamine-chondroitin treatment is gaining popularity among consumers because of proof of its effectiveness in recent scientific studies and because it is considered by many to be an ideal drug therapy—very effective with few, if any, side effects.   The number of testimonials that may be found on the web attesting to the effectiveness of the treatment is astounding.
    In light of recent scientific studies providing evidence that glucosamine and chondroitin do reduce or eliminate osteoarthritic pain, physicians and researchers speculate that the supplements may also offer similar benefits to sufferers of rheumatoid arthritis, ankylosing spondylitis, spinal disk degeneration, tendonitis, bursitis, and physical injuries to joints.  In addition, many advocates also feel that glucosamine supplements could play a preemptive role in eliminating the development of osteoarthritis. (http://webmd.lycos.com/content/article/1677.57489)

How does the glucosamine treatment compare to traditional methods of treatment?
     Traditionally, non-steroidal anti-inflammatory drugs (NSAIDs) have been prescribed to treat the symptoms of osteoarthritis.  These potent drugs primarily mask symptoms, causing stomach upset and even ulcer formation, as well as damage to the liver, kidneys, and gastrointestinal tract.  In contrast, glucosamine supplements have no serious side effects, causing only mild indigestion or headaches, which can usually be remedied by taking the supplement with food.  Glucosamine supplements do not interfere with any NSAIDs, aspirin, Tylenol, or other anti-inflammatory or analgesic medicines and may help patients reduce their level of dependence on these strong drugs.  Aspirin and other NSAIDs work by inhibiting the synthesis of prostaglandins, the substances within our bodies that mediate pain and inflammation.  The problem with this is that the drugs also inhibit the prostaglandins responsible for building and repairing cartilage tissue, leading to an actual worsening of the disease over time.  Glucosamine and chondroitin do not work by prostaglandin inhibition, so continued use of the supplements will not lead to progressive joint destruction, GI upset or bleeding, or strain on the liver and kidneys. (http://www.drmcdougall.com/Newsletter/sept_oct99.1.htm)

What evidence is offered in support of these claims?
     To date, there have been hundreds of scientific investigations and dozens of double blind studies conducted in hopes of scientifically confirming the testimonies to the wonders of glucosamine and chondroitin supplements, and medical benefits of the treatment have been cited in scientific literature for more than 35 years.  However, most of the studies conducted have been small-scale and foreign.  The National Institutes for Health has taken the initiative to change this, by allocating $6.6 million for a four-month, nine-center trial that is currently under way.  It involves over 1,000 osteoarthritis sufferers divided into four groups: one receiving glucosamine supplements only, one receiving chondroitin supplements only, one receiving both, and a placebo group.  Participants will undergo monthly evaluations of pain and ability to carry out daily chores.  In addition, x-rays taken at the beginning of the study will be compared to x-rays at the conclusion of the study. (http://webmd.lycos.com/content/article/1668.50297)
     To date, there have been several well-designed, double-blinded trials investigating the efficacy of the glucosamine-chondroitin treatment, most of which show improvements in the management of arthritis and few side effects.
    · A study conducted by Lopes Vaz (1982) evaluated the effectiveness of glucosamine sulfate (1,500 mg/day) versus ibuprofen (1,200 mg/day) in 32 patients with osteoarthritis, with approximately half the subjects undergoing the glucosamine treatment and half the ibuprofen treatment.  After two weeks of therapy, ibuprofen provided greater pain relief, but after eight weeks, glucosamine provided more relief.  This study used a pain scale and physicians’ observations to determine pain relief.
    · In an open trial of 1,208 patients, 1,500 mg of glucosamine were administered daily, with “good or sufficient” pain relief noted in an overwhelming 94% of patients at six and eight weeks follow-up.  There was a noted increase in arthritis symptoms after discontinuance of glucosamine as well.  The supplement was well tolerated with few side effects. (Tapadinhas, Rivera, and Bignamini, 1982)
    · In a placebo-controlled, double-blind study, oral glucosamine was administered at 1,500 mg/day to 80 inpatients, and pain was rated on a 1 to 4 scale.  Good or excellent results were reported by 29 of the 40 patients treated with glucosamine, and 17 of the 40 patients treated with the placebo.  No abnormalities were reported in routine laboratory tests, including complete blood count and glucose. (Drovanti, Bignamini, and Rovati, 1980)
    · One study by Pipitone (1991) tested the use of an oral chondroitin sulfate treatment (800 mg/day) against a placebo.  The study followed osteoarthritis patients over a six-month period.  After one month, no difference was noted between the two groups, but after three and six months, there was a significant difference in response, based on a pain scale and improvements in walking time.

    An extensive list of other studies that have been conducted may be found at http://www.drmcdougall.com/Newsletter/sept_oct99.1.htm.  Nearly every study has reported positive findings, with osteoarthritis patients claiming reduction or elimination of joint pain.  Many of the studies compared the use of glucosamine-chondroitin supplements with traditional treatments, with findings stating that the beneficial effects of glucosamine therapy are longer lasting, with fewer side effects.  Patients also reported a reduction in the use of potentially harmful NSAIDs.
What’s the downside? 
     While there are numerous studies touting the wonders of the glucosamine treatment, the supplement is not a miracle drug.  A recent study published in the Western Journal of Medicine suggests that a certain number of arthritic patients, mainly older, heavier, long-time sufferers, may experience no relief at all from glucosamine treatment.  Ninety-eight veteran patients with osteoarthritis and an average age of 65 volunteered to participate in the 2-month double-blind study by taking either a sugar pill or 500 mg glucosamine three times a day.  Pain intensity was measured while the participants walked and rested.  Study author Joseph P. Rindone, PharmD. and researcher at the VA Medical Center in Arizona, reports that “glucosamine was found to be no more effective than a placebo.”  Yet many who were dissatisfied with the glucosamine treatment reported better results after use of both glucosamine and chondroitin.
     "I guess you have to say the jury's still out [on glucosamine]," says Peter Sharkey, MD, who reviewed Rindone's study for WebMD. "I've got a lot of patients who say that it works. But the problem is you have a big placebo effect. Pain scores got better even for people taking the placebo." Sharkey is associate professor of orthopaedic surgery at the Rothman Institute at Thomas Jefferson University in Philadelphia. (http://webmd.lycos.com/content/article/1728.55691)
     One of the biggest drawbacks of the treatment is the high cost of the glucosamine and chondroitin supplements, which is magnified by recent investigations that illustrate the principle that “you don’t always get what you pay for.”  Researchers who conducted a recent study presented at the American Nutraceutical Association annual conference reported that some brands tested contained only miniscule amounts of the active ingredient, to an extent explaining disappointments in treatment effectiveness.  Among 14 glucosamine products, one had only 25% of the active ingredient claimed on the label, others fell significantly shy, and a few exceeded the amount claimed.  The results for the 11 chondroitin products tested were much worse, with one bottle containing almost no active ingredient, four bottles containing less than half the claimed amount, and disturbing variances among tablets of the same brand.  A second analysis was conducted that included 32 different brands, with only five of the products containing the amount of active ingredient the label claimed.  Even more unnerving results were provided by laboratory tests that tested five samples of the raw material used in chondroitin supplements.  Four of the five were found to have very low permeability, indicating a low likelihood of absorption by the body.  "What we're trying to do here is raise consciousness about dietary supplements... and it's not just glucosamine and chondroitin," says Natalie Eddington, PhD, director of the Pharmacokinetics-Biopharmaceutics Lab at the University of Maryland School of Pharmacy in Baltimore. "This is a problem with a number of dietary supplements and herbals on the market, because they're not regulated by a federal agency. So the buyer has to beware."  Consumers should consider using products that have been the subject of scientific research and are from reputable manufacturers, and they should be aware that the product they purchase is subject to wide variations in quality, potency, and efficacy. (http://webmd.lycos.com/content/article/1728.56163)
     There are few other precautions that must be kept in mind when beginning a glucosamine-chondroitin supplement treatment plan.  Patients taking the blood thinner, heparin, which has a molecular structure similar to chondroitin, should have blood clotting activity monitored.  Diabetics should consider the effects glucosamine could have on their blood sugar control, since glucosamine is an amino sugar.

Scientific Analysis of Data 
     There have been several review papers written discussing the results of glucosamine-chondroitin treatment studies.  McAlindon, LaValley, Gulin, and Felson (2000) conducted a meta-analysis that reviewed 15 randomized double-blind placebo-controlled trials of glucosamine and chodroitin (together and separately) for patients with osteoarthritis of the knee or hip.  Trials were included if they were longer than four weeks in duration, and an overall total of 1,710 patients were included.  The quality of each individual trial was evaluated by applying a validated assessment instrument, which assigns scores to the different aspects of how the trials were reportedly conducted.
     McAlindon et al. (2000) found empirical evidence for inflated estimates of benefits from the trials, suggested by observations of smaller effect sizes among the higher-quality and larger studies.  There was also statistical evidence of bias suggested by the absence of trials with small treatment effects.  This bias may arise from the selective publication of positive trials or premature termination of trials once a positive outcome was achieved.  Support for evidence of publication bias is also provided by the fact that most, if not all, of the trials received some amount of sponsorship from manufacturers of the compounds.  However, the authors of this study contacted authors of published articles and content experts in an attempt to determine if any unpublished trials existed, only to find none.  The trials as a whole showed that glucosamine has an effect size of 0.44, and chondroitin has an effect size of 0.94 (0 indicates equivalency with placebo, 0.2 to 0.8 indicates a moderate effect, and larger than 0.8 indicates a large effect).  In conclusion, McAlindon et al. found that trials testing the efficacy of glucosamine-chondroitin treatments on osteoarthritis patients demonstrated moderate to large effects, but the results of these trials may often be associated with exaggerated estimates of benefits.
     The study conducted by McAlindon et al. (2000) was further reviewed by Denham and Newton (2000), who found several problems with the meta-analysis, including: lack of attention to specifics (dosages, durations, etc.), lack of comparison with other known treatments, and significant differences between outcomes of the individual trials included in the study.  Towheed and Anastassiades (2000) expanded on the criticism of the study, adding that McAlindon et al. did not provide a description of the patients included in the study or address the risks of the glucosamine-chondroitin treatment in comparison with the placebo.  Since most trials have been of relatively short duration, the long-term effectiveness or amount of toxicity of the treatment has yet to be established.  Until high-quality studies, such as the National Institute of Health study, are completed, analyses such as the one provided by McAlindon et al. are our best source of information for analyzing the risks and benefits of the glucosamine treatment.

     There is an abundance of seemingly valid information concerning glucosamine-chondroitin supplemental therapy to be found on the web.  One site that provided a great deal of useful information was The McDougall Newsletter, a monthly publication written by Dr. McDougall, M.D.  The validity of this site seemed to be enhanced by the fact that there were no advertisements or links to make purchases; the information was presented simply and objectively after research by an actual physician.  Much of the other information I gathered was taken from articles on a site called WebMD, which has some impressive credentials.  Their content staff includes Emmy-Award winning journalists and board-certified physicians, boasting an impressive list of degrees in journalism, medical illustration, health communications, clinical informatics, nursing, and medicine, including internal medicine, cardiology, neurology, emergency medicine, women’s health, psychology, ophthalmology, and exercise physiology.  This site appears to be dedicated to quality and medical integrity, but one must keep in mind that the articles are written by journalists who aim to create articles that are not just informative, but also entertaining, and facts may be exaggerated to achieve this goal.  (http://webmd.lycos.com/medcast_channel_toc/1765)
    One must also question whether all the positive feedback concerning glucosamine supplements is partially hype, since there are no conclusive long-term, large-scale studies as of yet.  However, based on the available information found in medical journals and analyses of existing studies, I would say that it is safe to conclude that glucosamine supplements are relatively safe and effective.  There is no evidence to the contrary, and the number of success stories and the fact that conventional osteoarthritis treatments can and do cause long-term damage would lead me to advise sufferers to at least see if it has any personal positive effects.  In any case, it seems as though the worst damage the treatment could cause will be to your wallet, not your body.  The cost for this treatment runs about $30-60 a month and is not covered by insurance.  It will be interesting to learn of the findings of the current research by the National Institutes of Health and discover whether all the success stories are founded on actual science or are merely based on hype and hearsay.
     An additional interesting question that surfaces when discussing the glucosamine-chondroitin treatment is, “Why has it taken so long to catch on in the US?”  As noted by McCarty (1994), glucosamine has been used in Europe since 1969, and all studies to date have shown results with improvement in symptoms.  He says, “America’s massive, richly funded medicopharmaceutical complex has evinced not one shred of interest, undoubtedly because glucosamine is an unpatentable natural agent.”  In other words, since glucosamine is not a patentable prescription drug that the pharmaceutical industry could exploit for profit, they have no interest in promoting it.  However, it is impossible to hide the obvious benefits of the treatment from the American consumer.



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