Nutraceutical options for osteoarthritis in orthopedics and sports medicine

John Bergfeld, MD: Millions of patients in the United States suffer from conditions and diseases associated with joint discomfort and cartilage breakdown, especially osteoarthritis (OA). Developments in pharmacology, such as nutraceuticals, offer new approaches to joint health.

What are some factors that affect the prevalence of OA?

Nicholas A. DiNubile, MD: There are many predisposing factors for OA, including genetics, prior injury, obesity and sex; women have a greater incidence of OA than men (Figure 1).¹ Extended lifespan is another factor that could explain the higher incidence of OA in our population, ie, by living longer, the likelihood of developing OA in joints such as the knee or hip as well as certain joints in the hand increases. Despite the implications of longer projected lifespans and the incidence of OA, the majority of our joints do not develop arthritis. Clearly we need to learn more about this multifactorial disease.

The American Academy of Orthopaedic Surgeons’ (AAOS) data indicate a significant increase in the incidence of OA in people between the ages of 55 and 64 years — the baby boomer generation.² This group has become more active on their aging frame than prior generations and therefore has accumulated more injuries over time.

Figure 1: Age-adjusted prevalence of physician-diagnosed arthritis among adults in the United States from 2007-2009, by sex and body mass index (BMI) category. For men and women, the prevalence of age-adjusted arthritis increased significantly with increasing BMI (P <.001 for trend). The age-adjusted prevalence of OA among people who were obese (25.2% for men and 33.8% for women) was nearly double that of people who are underweight/normal weight (13.8% for men and 18.9% for women). Source: CDC. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation— United States, 2007-2009. MMWR. 2010;59(39):1261-1265.

Allan H. Morton, DO: Although the focus in my practice continues to be treating people with rheumatoid arthritis (RA), there is now a greater emphasis on treating those with OA because of the number of patients affected by the disease, especially given the aging baby boomer population.

DiNubile: Two segments of the population often affected by OA are those who are obese and those who are athletic. Obesity amplifies the effects of damaged joints, especially if alignment issues are present. Depending on the activity being performed, every extra pound of weight a person carries can affect the knee or hip as if it were 5 to 7 extra pounds.

“... [T]here is now a greater emphasis on treating those with OA because of the number of patients affected by the disease, especially given the aging baby boomer population.”

— Allan H. Morton, DO

Athletes often experience premature joint aging due to injuries and repetitive overuse of joints. Depending on the sport played, signs of arthritis are visible in different joints. For example, compared to people who do not play sports, soccer players are more likely to have knee OA, basketball players are more likely to have arthritic change around the ankle, dancers are more likely to have OA in their hips, and gymnasts, football lineman, and powerlifters are more likely to have OA in the spine region. In most of these instances, the prevalence of OA in these athletes is most likely the effect of repetitive microtrauma. When there is an acute injury, such as an ACL tear, OA is still prevalent, even with the modern minimally invasive repair techniques that allow for a fairly predictable recovery and return to sport.

The implications of overuse especially affect baby boomers, who, as a whole, maintain an active lifestyle. Although advances in health and science have lengthened the human lifespan from 46 years at the turn of the last century to almost 80 years today, our musculoskeletal structure has not evolved fast enough to accommodate longer, active lives. Therefore, the incidence of musculoskeletal ailments in this population, including OA, and the associated need for joint replacement has increased.

Jeffrey R. Dugas, MD: In today’s society there is an increasing emphasis on a healthy lifestyle, which includes frequent exercise to promote a healthy metabolism. Every American is aware of the benefits of exercise, and this has led to a huge increase in the health and fitness promotion industry as well as in the nutraceutical industry. The increase in exercise participation and the frequency and intensity of exercise is rising, which will likely increase the injury risk among adults as well as the prevalence of degenerative OA.

Edward R. McDevitt, MD: Young athletes incur injuries that can lead to early OA later in life. The STOP (Sports Trauma and Overuse Prevention) Sports Injuries campaign, initiated by the American Orthopaedic Society for Sports Medicine (AOSSM) and James R. Andrews, MD, is critical because injuries continue to affect patients as they age. If injuries could be prevented, patients, as well as society, which is already burdened by the growing cost of health care, would benefit.

DiNubile: The number of young female athletes injured, especially with ACL tears, is considerable. Even after successful injury treatment, it is likely that these patients will develop arthritis in 20 to 30 years.

Claude T. Moorman III, MD: Patients who incur externally generated injuries or experience misalignment that affects the joint should also be considered at risk for OA. Many young athletes incur radial tears to the lateral meniscus — an injury also common in professional athletes. I treat many lacrosse and football players, and one of the most at-risk areas for these patients is their knees. Medical interventions that augment the ability of these injuries to properly heal are imperative.

Bergfeld: What is the cause of OA in patients who have not been subject to the mechanical forces related to OA, eg, previous injury, obesity, overuse? Is there another etiology that causes articular cartilage breakdown to occur?

Morton: Cartilage breakdown is also prevalent in people with hereditary erosive OA, genetics-based OA or hypermobile joints. Although OA is considered one disease, it is actually a spectrum of diseases due to the many etiologies that contribute to it.

For example, primary OA is not prevalent in the ankle, but is commonly found in the hip and knee. One hypothesis to explain this difference is that ankle cartilage differs from hip and knee cartilage and therefore is spared from primary OA.

Treatment options for OA

Bergfeld: What are the available treatment options for joint discomfort and cartilage breakdown?

Dugas: In patients with knee OA, my approach tends to be multifaceted. Patients who have unicompartmental disease from a weight-bearing standpoint should wear well-fitted or custom unloader braces as well as orthotics, such as shoe inserts, that tilt their heels away from the affected compartment. These mechanical options are good adjuncts to nutraceutical supplements, injectables, physical therapy and NSAIDs. I also counsel patients about exercises that can be done without placing tremendous stress on their lower extremity joints. In particular, I recommend swimming and the use of recumbent bicycles, rowing machines and elliptical trainers.

Morton: As a rheumatologist caring for people with musculoskeletal diseases, I frequently use bracing methods, such as splints, tape, back supports and unloader knee supports in my practice. When discussing treatment methods with my patients, I review four types of options: surgical, nonsurgical, nonpharmacologic and pharmacologic.

“My first line of defense for treating OA is recommending conservative measures, including nutraceuticals, exercise and weight loss.”

— Nicholas A. DiNubile, MD

Before recommending orthopedic evaluation for possible surgery, I employ nonpharmacologic options, such as quadriceps strengthening, weight loss or assistive devices such as knee and back supports. When treating OA, I recommend nutraceuticals, ie, naturally occurring substances that have proposed medicinal and bioactive benefits, because they are beneficial for most patients. Even if patients indicate that their initial experience with a nutraceutical did not work, I would suggest trying another one.

I still use NSAIDs in my practice, but I choose my patients carefully to avoid side effects. I often prescribe concomitant gastro-protective medications. Because there are no FDA-approved medications to slow the progression of OA, I recommend nutraceuticals for both symptomatic relief and potential disease-modifying benefit.

DiNubile: My first line of defense for treating OA is recommending conservative measures, including nutraceuticals, exercise and weight loss (Figure 2). For patients with significant swelling, pain or synovitis, I will also suggest an oral NSAID. If a patient’s symptoms persist, I pursue additional treatment options.

Data have shown that viscosupplementation is more likely to be effective in the earlier phases of knee OA than in the advanced stages. For baby boomers or younger patients who are not ready for a knee replacement, I use viscosupplementation more and corticosteroids less, because I see viscosupplementation as a safer long-term strategy. Potential chondroprotective effects are greater with viscosupplementation than with corticosteroids, which provide short-term relief and, if used repetitively, can be detrimental to articular cartilage. For patients who require immediate pain relief, or those with more acute swelling or synovitis, I will use intra-articular steroids.

Figure 2: Lifestyle and pharmacologic treatment options for OA. Source: Nicholas A. DiNubile, MD

Bergfeld: In addition to these recommendations, I will recommend a single visit with a physical therapist to instruct in proper strength training and joint stretching.

Do you use hyaluronic acid (HA) injections when treating patients with knee OA?

Robert Schenck Jr., MD: It depends on the patient and the severity of his or her OA. For example, if the patient is older and has a severely arthritic knee, a total knee replacement will probably be necessary. If a patient has OA and joint effusion, I might first try aspiration and corticosteroid injection, limiting the carrying agent. After trying this regimen, I generally try one series of HA injections.

Another factor to consider is that HA injections require insurance approval. Some providers may require a patient to first undergo physical therapy and corticosteroid injections. If I am treating a younger, active patient with symptoms of OA who may have incurred an injury such as an ACL tear, I will use HA injections but not a steroid, because corticosteroids have been shown to be deleterious to normal hyaline cartilage. Furthermore, the National Collegiate Athletic Association does not recommend corticosteroid injections in the knee or shoulder routinely for the young collegiate athlete.

Moorman: HA injections are beneficial for patients who may have already undergone an arthroscopic procedure, but who are not yet candidates for a joint replacement. Although I do feel that more patients benefit from the use of oral nutraceuticals, such as glucosamine and chondroitin sulfate with avocado soybean unsaponifiables (ASU), HA should not be completely ruled out as an alternative treatment to surgery in properly selected patients.

Morton: Some oral and topical HA products might be considered nutraceuticals, but none have indicated evidence of efficacy.

I am an aggressive injector of HAs, but my initial treatment regimen focuses on NSAIDs and/or analgesic use in combination with a nutraceutical and physical therapy. If the patient fails to respond to treatment in 1 to 2 months, I would consider intra-articular steroids. If the patient does not experience 3 months of relief, I would consider HA injections.

McDevitt: I always try other treatment options before HA because weight loss, specific exercises that do not stress the involved joints and core strengthening often ease a patient’s pain. I would like to see a long-term randomized study that compares the effects of HA with those of a placebo.

The dangers of using cortisone, which has been administered for years as an injection in the joints, should be noted. If any of my patients ask for cortisone because it worked when administered to them 10 years ago, I would educate them on safer long-term options. The most common recommendation I have for most of my patients is to eat less and exercise more. Through weight reduction and a low-impact exercise program, many patients will achieve dramatic improvements in their arthritis pain. A simple knee sleeve for patients with knee arthritis is also helpful. If these conservative measures are not successful, I recommend HA injections.

Moorman: In my practice, I have a cadre of active 50- to 80-year-old patients who do not want joint replacements and who do not benefit from arthroscopy, which, based on recent literature, pertains to patients whose pain predominantly stems from arthritis.³

“Nutraceuticals ... are an attractive option because many ... patients are already familiar with these treatments and are comfortable using them.”

— Claude T. Moorman III, MD

From a mechanical perspective, I might use off-loader braces to externally immobilize or offload the joint. Nutraceuticals, such as glucosamine and chondroitin sulfate, and more recently the formula combined with ASU, are an attractive option because many of these patients are already familiar with these treatments and are comfortable using them. Therefore, it is simply a matter of determining which product is best for them.

As I have become more familiar with the literature, I have also begun to consider that patients in their 30s who have early signs of distal interphalangeal joint disease can benefit from nutraceutical use.

Bergfeld: Do nutraceuticals fit into different chemical categories?

Morton: Nutraceuticals, such as glucosamine, chondroitin, ASU, green tea and manganese seem to have more similarities than differences regarding their mechanisms of action (Figure 3, Table).⁴

Our goal for our patients is to decrease pain and inflammation, maintain or improve function and retard disease progression if possible. In this regard, preventing damage to subchondral bone, cartilage, joint space narrowing and osteophyte formation is the goal. What contributes to this damage is a pattern of inflammatory mediators that interact in a way to cause these deleterious effects.

There is scientific evidence that nutraceuticals, such as those mentioned above, alone or in combination, inhibit many of these pathways to prevent this inflammatory and destructive process. Thus, when I start a patient on a nutraceutical, I hope that he or she experiences symptom relief, but my main concern is changing the natural history of the disease.

Bergfeld: Can a nutraceutical potentiate the effect of the nonsteroidal?

Morton: Yes. Studies indicate that nutraceutical use decreases analgesic and NSAID use. Pain scales have shown a decrease in visual analogue scale (VAS) scores and the functional index has shown improvement with nutraceutical use.^5,6

Bergfeld: What are some potential contraindications for drug and nondrug therapies available for OA treatment?

McDevitt: The contraindications for NSAIDs include gastrointestinal (GI) bleeding or adverse effects to the kidneys or liver. Some patients worry about taking a glucosamine product because they have diabetes, but I inform them no data support this concern. I am unaware of any studies that indicate nutraceutical use is dangerous. Overall, this treatment option seems relatively safe compared with available drug therapies.

I stress the importance of telling any medical professional what nutraceuticals the patient uses, because some nutraceuticals — especially garlic, ginseng and gingko — affect bleeding time. If used in conjunction with NSAIDs, the risk of GI problems increases.

DiNubile: The same patients who, in the past, requested NSAIDs such as rofecoxib or valdecoxib, now even may avoid the use of ibuprofen or naproxen. Although some patients may be overreacting, their concerns about the potential adverse effects of NSAIDs are understandable. A patient must consider if the potential benefits to the musculoskeletal system outweigh the potential risks to the heart, liver, kidneys and stomach. I think it is right to be cautious with NSAID use, and I often recommend that my patients reduce or discontinue their use of NSAIDs.

ASU

Bergfeld: Recently, studies have indicated that ASU complements the effects of chondroitin sulfate with glucosamine and protects cartilage, leading to improved joint function (Figure 3). Does the anabolic effect of glucosamine, chondroitin sulfate and ASU stimulate chondrocyte activity?^7-11

Figure 3: ASU, in combination with chondroitin sulfate, glucosamine and epigallocatechin gallate, modulates inflammatory response and cartilage breakdown. Source: Nutramax Laboratories, Inc.

Morton: I am unsure whether chondroitin and glucosamine stimulate chondrocyte production; however, they do increase proteoglycans, which is part of the joint matrix.

Chondroitin sulfate does have an anti-catabolic effect on enzymes that degrades cartilage and increases the synthesis of HA, which is obviously important for joint composition. Bruyere and colleagues¹² studied joint replacement and glucosamine sulfate treatment. The study treated participants for 12 months to 3 years and included a 5-year follow up. Of the 144 participants treated, nine had total joint replacement; of the 131 participants not treated, 19 had total joint replacement. Thus, approximately 50% fewer treated patients underwent total joint replacement.

Bergfeld: Do data indicate that combining chondroitin sulfate and glucosamine with ASU will potentiate their effects?

DiNubile: Yes. This combination creates synergy where the whole is greater than the sum of its parts. Just as the combination of chondroitin sulfate with glucosamine has been shown to be more effective than either agent alone, the addition of ASU provides additional synergistic effects. There also appears to be a quicker onset of action, in terms of symptomatic relief, with the addition of ASU (Table).

Source: DiNubile NA. A potential role of avocado and soybean-based nutritional supplements in the management of osteoarthritis—a review. The Physician and Sportsmedicine. 2010;38(2):71-81. Reprinted with permission from JTE Multimedia.

Morton: Glucosamine positively enhances chondroitin sulfate, and ASU also has many independent properties that are beneficial. Glucosamine chondroitin sulfate in combination with ASU may be one of our better disease-modifying osteoarthritis drugs (DMOADs). A five-, six-, or eight-arm study following a large number of individuals would probably be needed to efficiently study each ingredient and its effect. There is a lot of overlap, but there is also some potentiation.

DiNubile: The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) study described the synergy between glucosamine and chondroitin sulfate. When combined, the two compounds had a more powerful effect, even though a final determination could not be made for the moderate-to-severe group because of an inadequate patient sample size.¹³

Those in the glucosamine/chondroitin sulfate group actually outperformed the celecoxib (Celebrex, Pfizer, Inc.) and placebo groups for those with moderate-to-severe OA.

The combinations of glucosamine, chondroitin sulfate and ASU have been shown to work in numerous in vitro studies, especially with regard to anti-inflammatory effects.^7-11

As mentioned, ASU may also have a faster onset. From my experience, it appears that patients taking glucosamine and chondroitin sulfate with ASU may feel its effects more quickly. Generally, when I recommend glucosamine and chondroitin sulfate, I tell patients that they might need to wait 2 to 3 months to see the full results. However, in one study of glucosamine and chondroitin sulfate, participants showed improvement by 8 weeks.

Published Research

Bergfeld: Does any published research support the product claims for nutraceuticals?

Morton: Basic science research in animal models demonstrates the beneficial effects of nutraceuticals, including a decrease in inflammatory mediators such as nitric oxide as well as joint and cartilage protection.

A postcontusive rabbit study compared joint damage between rabbits treated with ASU to untreated rabbits.¹⁴ The results of the study indicated less joint damage in the treated rabbits than in the untreated rabbits.

In June 2010, PubMed listed two studies that showed that chondroitin sulfate decreases joint space loss compared with placebo.^15,16 At the annual European League Against Rheumatism (EULAR) Conference in June 2010, Maheu presented a study called Eradias, a 3-year, prospective, blinded study of the effects of ASU on hip OA that indicated a decrease in narrowing of the joint space of 20% over 3 years.¹⁷

McDevitt: Like many patients, I was skeptical when glucosamine and chondroitin sulfate first came on the market. Although I reviewed the European and veterinary studies, the most effective data for me came from personal experience.

My 12-year-old Golden Retriever was having trouble walking. When I took her to the veterinarian, the doctor recommended glucosamine and chondroitin sulfate.

I said, “Glucosamine and chondroitin sulfate? That is just placebo effect,” to which the doctor replied, “Dogs do not know placebo effect. Try it.”

Six weeks later, my dog was running again. After that, I started taking her medicine because I figured it might help an old dog like me, too.

Bergfeld: There is no question that veterinary medicine has conducted useful studies that have shown how use of glucosamine and chondroitin sulfate has improved lameness in equines. The veterinary literature is strong and perhaps it should be considered more in our own practice.

What data are available that notes the effects of ASU on OA?

Morton: A recent study by Pavelka and colleagues¹⁸ indicated that a 300-mg dose of ASU and a 1,200-mg dose of chondroitin sulfate garnered similar improvements in both the WOMAC and Lequesne indexes.

Moorman: The addition of ASU to glucosamine and chondroitin sulfate is exciting because patients tend to respond quicker to this combination. I have taken these products myself, and my experience confirms this observation.

As Dr. Morton has mentioned, the more recent studies indicate that we are coming close to nonsteroidal efficacy with ASU. I do not think we could have said that about glucosamine and chondroitin alone.

DiNubile: Many of the original studies in the rheumatology literature have shown the effectiveness of glucosamine and chondroitin sulfate in the hand.^19,20

GAIT Study

Bergfeld: The GAIT study, published in 2006, indicated that glucosamine and chondroitin sulfate, in combination or alone, did not reduce pain effectively in the overall study group with OA of the knee.¹³ These findings were supported by the AAOS, which does not recommend the use of nutraceuticals for OA.

How do you feel about this study’s findings and its implications for use of glucosamine and chondroitin sulfate in your practice?

Schenck: I think that the GAIT study provided a credible randomized trial that studied glucosamine and chondroitin sulfate. More studies such as this, which focus on randomized blinded trials with glucosamine and chondroitin sulfate, should be performed.

The GAIT study eliminated many of the problems seen in previous research, ie, studies that were industry supported, nonblinded or nonrandomized. It may not have provided the results that clinicians who use nutraceuticals wanted, but clearly it was a well done, randomized trial.

McDevitt: I am concerned with how trustworthy the results of the GAIT study are because so many participants were taking acetaminophen at the same time as the glucosamine and chondroitin sulfate. I question whether the high placebo effect was a result of this. For me, the study’s results would be more reliable if participants had only been given the glucosamine and chondroitin sulfate.

“The addition of ASU to glucosamine and chondroitin sulfate is exciting because patients tend to respond quicker to this combination.”

— Claude T. Moorman III, MD

Morton: I also question the high placebo effect reported in the GAIT study. A 60% placebo rate is questionable, because the percentage is generally 25% or 30% in a pain-relief study. Because of this, and the other research that supports the benefits of its use, I still prescribe glucosamine and chondroitin sulfate despite the GAIT study’s results.

DiNubile: The GAIT study raised more questions than it gave answers. The study’s moderate-to-severe group did well with supplements; however, there were not enough participants enrolled in this group to achieve statistical significance. Even the researchers involved in the GAIT study concluded that more research needs to be conducted.

Therefore, I was disappointed to see that the AAOS based their decision to not recommend glucosamine and chondroitin sulfate solely on this study. I feel that these guidelines need to be revised, not only to reconsider glucosamine and chondroitin sulfate, but also to consider the combination with ASU and to provide a better evaluation of the viscosupplementation literature.

Regardless of the current AAOS guidelines, I will continue to recommend glucosamine and chondroitin sulfate to my patients. I base this decision on the very favorable safety profile of these compounds, and on the wealth of literature — human, veterinary, in vitro and in vivo — currently available. Patients are understandably more reluctant to use NSAIDs, especially on a chronic basis. Joint supplements have helped fill that void in my practice.

Regulation

Bergfeld: What are the current regulation standards for nutraceuticals in the United States?

McDevitt: The Dietary Supplement Health and Education Act (DSHEA), which allows patients to obtain dietary supplements without prescription, was passed in 1994. According to DSHEA, a dietary supplement is broadly defined as any nontobacco product “intended to supplement the diet,” including a vitamin, mineral, herb or other botanical, amino acid, a dietary substance for use by man to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, extract, or combination of any of the preceding substances.²¹

This act was highly lobbied by the supplement industry and, once passed, the number of supplements sold in the United States dramatically increased. In 2009 it was estimated that 59% of Americans were taking dietary supplement.²² The DSHEA states that a supplement is something used to augment your diet, ie, a mineral, herb or amino acid, but not indicated as a food and is intended to be used as a pill, capsule, tablet or liquid.²¹

However, Congress chose to exclude dietary supplements from their definition of a food additive. Dietary supplements are therefore regulated like a food or drug, based on their label claims, although there are exemptions for dietary supplements from normal labeling rules.²¹ This made a significant difference in what a company could manufacture and how supplements were viewed and handled in the United States.

Prior to DSHEA, a nutraceutical such as glucosamine or chondroitin sulfate would have come under FDA regulations. Now, the inclusion of the statement “These statements have not been evaluated by the FDA and this product is not intended to diagnose, treat, cure or prevent any disease” is required on dietary supplement labels. Because of this, companies are prohibited from making product claims regarding their effect on the disease process, ie, they can indicate that the product can reduce the risk of a disease, but they cannot say that it actually treats a disease.

Bergfeld: How can patients be assured that a product meets label claims when purchasing a nutraceutical such as glucosamine and chondroitin sulfate with ASU?

“Contamination is a major concern with supplements...This has affected many consumers, especially athletes.”

— Edward R. McDevitt, MD

McDevitt: The FDA has issued Good Manufacturing Practices (GMP), the nutraceutical regulation that specifies labeling must indicate the product’s dosage, directions for use and manufacturer’s information. GMP also requires consistent manufacturing processes, for example, identity, purity, strength and composition, for dietary supplements.

Contamination is a major concern with supplements because some companies will run multiple products down the same assembly line without cleaning the machinery.²³ This has affected many consumers, especially athletes, who have used a product contaminated with anabolic steroids from another product, causing them to test positive during drug testing. Therefore, knowing which nutraceuticals are efficiently regulated is important for physicians treating athletes, who expect their health care providers to know which supplements are approved by the World Anti-Doping Association.

The FDA conducts quality control inspections at companies’ facilities, but because of budgetary cuts, regular inspection is generally only conducted at larger manufacturing facilities. The Federal Trade Commission is responsible for investigating potential unfair or deceptive practices that affect consumers.

DiNubile: These products can also meet label claims while the bioactivity of the compound being used varies tremendously when compared with other products.

For example, a product might contain the amount of glucosamine or chondroitin specified on the label, but the manufacturer could be using a mixture of five different types of glucosamine or chondroitin, some of which are very bioactive and some of which are not bioactive at all. Therefore, no matter how informed the consumer or physician is about the product, they would not be able to glean this information from the label.

Cosamin DS (Nutramax Laboratories, Inc.), the original glucosamine and chondroitin sulfate combination, has always been manufactured following pharmaceutical GMP standards. This is not always the case because some companies use a lower quality, or significantly smaller dosage because of the cost of chondroitin. Independent studies have shown tremendous variation in the actual chondroitin sulfate content of different products with many failing to meet stated label claim.²⁴

Bergfeld: How can a patient determine which nutraceuticals meet label claims?

DiNubile: Current U.S. laws and regulations do not require supplements to meet label claims. Therefore, a label can state that its product has 1,200 mg of chondroitin sulfate when it actually contains a lower amount. To help patients determine which nutraceuticals meet label claims, I provide them with print materials and suggest online resources for them to visit.

Examples of these online resources include www.consumerlabs.com, which independently tests different brands to see whether they meet label claims, and www.NSF.org, which not only tests and certifies brands, but also checks for undesired contaminants and additives.

Morton: There may also be discrepancies between what generic medications indicate on their labels and what the products actually contain. According to the FDA, an A-level generic needs the ingredients in their product to fall within a 20% range of what the label claims. This would be like having a generic dollar bill worth between $0.80 and $1.20.

Bergfeld: What resources can we provide patients to assure them of a product’s standards for quality control?

Dugas: Unfortunately, there is no perfect way for consumers to verify the contents of any supplement or nutraceutical. When advising patients, I encourage them to use products produced by reputable domestic companies. I also encourage them to research the proposed benefit of any supplement and recommend www.NSF.org if a patient wishes to get more information.

McDevitt: NSF Certified for Sport, also regulated by www.NSF.org, tests and certifies that products contain the identity and quantity of dietary ingredients declared on the product label, and that they do not contain unacceptable quantities of unwanted contaminants for the recommended serving size listed on the product label.

“Many doctors and pharmacists might say to buy the cheapest [supplements] because they are all the same, but there is nothing further from the truth.”

— Nicholas DiNubile, MD

DiNubile: Nutraceuticals are evaluated by the NSF; however, product evaluation is voluntary, so the supplement companies are not mandated to participate. The NSF Certified for Sport program is important for athletes. When a supplement is certified for sport it means that quantitative analysis has been conducted to determine whether the supplement meets its label claims. It also ensures the absence of additional additives or contaminants, including banned substances, that could result in disqualification, penalties, fines, suspensions or even legal action for athletes.

When I have patients take supplements, I explain that the brand they select is essential because data show that a significant number of companies do not meet their label claims. Many doctors and pharmacists might say to buy the cheapest one because they are all the same, but there is nothing further from the truth. Therefore, I routinely recommend Cosamin DS and Cosamin ASU (Nutramax Laboratories, Inc.) because of their commitment to research in the field.

Dugas: When it comes to the athletes for whom we provide care, I like to get a nutritionist involved in the discussion. Particularly in the warmer southern climate I live in, nutrition and hydration are of paramount importance. Any supplement that an athlete wants to use should be carefully considered under the umbrella of their overall nutrition.

Bergfeld: Is there a difference in how nutraceuticals are regulated in Europe?

McDevitt: Supplements in Europe are much more controlled than they are in the United States, so what might be nonpharmacologic here might be prescription based in Europe.

Future Recommendations

Bergfeld: What future recommendations do you feel would be beneficial for the nutraceutical industry?

Morton: More studies focusing on nutraceuticals and their potential cartilage regeneration benefits should be conducted. A registry, a real-world collection of data, might be considered for physicians who recommend nutraceuticals to their patients. It might capture patient demographics, which diseases are being treated, what treatment is being recommended, duration of therapy and some type of outcome such as a functional index or pain scale. Registry data are common in Europe and are slowly being developed in the United States. This allows for a large number of patients to be studied without strict adherence to clinical trials.

Bergfeld: The data that could be gleaned from a registry would be extremely beneficial; however, creating such a database is labor intensive and costly, and significant maintenance must be performed to ensure the data are accurate. I think the investment in such a system is worthwhile and the benefit to physicians would be invaluable.

McDevitt: One of the most exciting areas of research in orthopedics involves biologics, such as various growth factors. For example, the growth factors of platelet-rich plasma have the potential to help patients with musculoskeletal ailments. Further studies are being done on proteins that may be able to reverse the effects of arthritic joints. Although it is unclear what discoveries will result from this research, I am certain that exciting new information will be coming soon.

Morton: Stem cell research is another exciting development in the field of orthopedics. A study will be started in England soon, where stem cells will be used to attempt to regenerate damaged cartilage to treat or even prevent OA.²⁵ Biomarkers are important in monitoring the progression of the disease. There has also been discussion of using acoustical techniques to listen to joints to diagnose pathology.²⁶

DiNubile: Although MRI technology has been great at visualizing meniscus, ligaments and even stress fractures, to date, it has not been as efficient at assessing articular cartilage. The newer quantitative MRI systems that are evolving, but are not yet widely available, may also be beneficial because they can color map articular cartilage quantitatively. Once this technology is further developed, we may be able to gain a clearer understanding of how nutraceuticals work, how quickly they work and whether they can help repair chondral defects or stimulate cartilage regrowth.

Morton: A recent study presented by Pelletier and colleagues at the 2010 EULAR Congress used MRI to evaluate the effects of chondroitin sulfate as a DMOAD on cartilage volume, bone marrow lesions and synovitis.²⁷ Their findings indicated that chondroitin sulfate prevented loss of cartilage volume in as little as 6 months and the bone marrow lesion was affected between 6 and 12 months. The study also demonstrated that combining NSAIDs with chondroitin sulfate reduced the severity of synovitis.

DiNubile: Advances in our field will not only be accomplished through technology, but also by orthopedists educating themselves and their patients about the potential benefits of nutraceuticals and other natural remedies. A significant number of our patients are currently taking nutraceuticals, regardless of what the current recommendations for their use may be. Therefore, in order to best treat our patients, it is our obligation to learn more about this potential treatment option so we can assist them in making informed decisions about nutraceuticals and other less invasive approaches, regardless of our treatment preferences.

Our patients have a strong interest in alternative medicine as well as in more natural approaches, so we need to keep an open mind as scientific data continue to accumulate in this relatively new area. Ultimately, we must rely on science to guide treatment recommendations.

“Continued research in the area of nutraceuticals and supplements will be an important part of improved fitness, longevity and disease treatment and prevention as we move forward.”

— Jeffrey R. Dugas, MD

Dugas: As discussed earlier, we are in the midst of an explosion of knowledge in the health and fitness field. Our society knows that they should eat smart and exercise as part of a healthy lifestyle. Part of our healthy lifestyle is making sure that our diets are balanced with enough nutrients to support the changing needs of our bodies. Age, injury, disease, environment and genetics all affect the needs of our bodies. Continued research in the area of nutraceuticals and supplements will be an important part of improved fitness, longevity and disease treatment and prevention as we move forward.

Conclusion

Bergfeld: I would like to thank the panel for their time, effort and expertise on the subject of nutraceutical options in the context of orthopedics and sports medicine and the sponsor of this symposium, Nutramax Laboratories, Inc. The information provided throughout this discussion contributes to a greater depth of knowledge of the different treatment options available for OA, both from a clinical and a sports medicine standpoint. Through careful review of the literature and first-hand experience in practice, the general medical community is becoming more aware of and more willing to consider the available options for OA.

References

1. CDC. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation—United States, 2007-2009. MWWR. 2010;59(39):1261-1265.
2. AAOS. United States Bone and Joint Decade: The Burden of Musculoskeletal Diseases in the United States. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2008.
3. Moseley JB, O’Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347(2):81-88.
4. DiNubile NA. A potential role of avocado and soybean-based nutritional supplements in the management of osteoarthritis—a review. The Physician and Sportsmedicine. 2010;38(2):71-81.
5. Appelboum T, Schuemans J, Verbruggen G, et al. Symptoms of modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis. A double blind, prospective, placebo-controlled study. Scand J Rheumatol. 2001;304(4):242-247.
6. 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(5):343-350.
7. Au RY, Au AY, Snow GE, Rashmir-Raven A, Frondoza CG. Cyclooxygenase-2 gene expression and prostaglandin-E2 production in activated equine osteoblasts are inhibited by avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate [abstract]. Presented at the 2007 American College of Veterinary Internal Medicine (ACVIM) Forum Proceedings. Sun Valley, ID; March 3-10, 2007.
8. Au AY, Au RY, Rashmir-Raven AM, Frondoza CG. Downregulation of cyclooxygenase-2 expression and prostaglandin-E2 production in equine chondrocytes and osteoblasts by avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate. Proc Equine Sci Soc. 2007.
9. Au RY, Au AY, Rashmir-Raven A, Frondoza CG. Inhibition of pro-inflammatory gene expression in chondrocytes, monocytes, and fibroblasts by the combination of avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate. FASEB J. 2007;21(6):702-707.
10. Au RY, Au AY, Rashmir-Raven AM, Frondoza CG. Pro-inflammatory gene expression in chondrocytes and monocyte/macrophages is inhibited by the combination of avocado soybean unsaponifiables, glucosamine, and chondroitin sulfate [abstract]. Presented at the 34th Annual Conference of the Veterinary Orthopedic Society. 2007. Chicago.
11. Frondoza CG, Heinecke LF, Grzanna MW, Au AY, Rashmir-Raven AM. Modulation of metalloproteinase expression by the combination of avocado soy unsaponifiables, glucosamine hydrochloride and chondroitin sulfate. Presented at the 8th World Congress of the International Cartilage Repair Society. Miami, FL: May 23-26, 2009.
12. 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. 2008;16(2):254-260.
13. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795-808.
14. Mazières B, Tempesta C, Tiechard M, Vaguier G. 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.
15. Kahan A, Uebelhart D, De Vathaire F, et al. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2009;60(2):524-533.
16. Black C, Clar C, Henderson R, et al. The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technol Assess. 2009;(52):1-148.
17. Maheu E, Cadet C, Marty M, et al. Evaluation of the structure-modifying effect of avocado-soybean unsaponifiables (ASU) in hip osteoarthritis (OA): results of the Eradias study—a 3-year prospective, randomized, double-blind, placebo controlled trial. Presented at the 2010 Annual European Congress of Rheumatology. Rome, Italy; June 16-19, 2010.
18. Pavelka K, Coste P, Géher P, et al. Efficacy and safety of piascledine 300 versus chondroitin sulfate in a 6 months treatment plus 2 months observation in patients with osteoarthritis of the knee. Clin Rheumatol. 2010;29(6): 659-670.
19. Uebelhart D. Clinical review of chondroitin sulfate in osteoarthritis. Osteoarthritis Cartilage. 2008;16:S19-S21.
20. Verbruggen G, Goemaere S, Veys EM. Systems to assess the progression of finger joint osteoarthritis and the effects of disease modifying osteoarthritis drugs. Clin Rheumatol. 2002;21:231-243.
21. DSHEA. 21 USC §321(ff) [DSHEA §3(a)].1994.
22. National Wellness Association. Exploring consumer attitudes about dietary supplement barometer survey. Available at: http://nationalwellnessassociation.com/News/Survey_Results.htm. Accessed October 8, 2010.
23. Dangerous Supplements. Consum Reports. 2010:16-23.
24. Adebowale A, Cox D, Liang Z, et al. Analysis of glucosamine and chondroitin sulfate content in marketed products and the Caco-2 permeability of chondroitin sulfate raw materials. J Amer Nutraceutical Assoc. 2000;3(1):37-44.
25. Scientists in new stem cell research that could prevent osteoarthritis. Arthritis Today [serial online]. 2010;148:10. Available at: http://www.arthritisresearchuk.org/PDF/ArthritisToday%20SMALL.pdf. Accessed August 30, 2010.
26. Kwong KSC, Huang X, Cheng JCY, et al. Acoustic transmission in normal human hips: structural testing of joint symmetry. Med Eng Phys. 2003;25(10): 811-816.
27. Pelletier JP, Wildi LM, Raynauld JP, et al. Treatment with chondroitin sulfate reduces cartilage volume loss in knee OA patients assessed by MRI: a randomized, double-blind placebo controlled pilot study. Poster presented at the 2010 EULAR congress. Rome, Italy: June 16-19, 2010.