WHAT IS OSTEOARTHRITIS?

Osteoarthritis, also known as degenerative joint disease, is the most common arthritic disease. Scientists now believe osteoarthritis results from a combination of genetic abnormalities and joint injuries. In this disorder, an affected joint experiences a progressive loss of cartilage, the slippery material that cushions the ends of bones. As a result, the bone beneath the cartilage undergoes changes that lead to bony overgrowth. The tissue that lines the joint can become inflamed, the ligaments can loosen, and the associated muscles can weaken. The sufferer experiences pain when the joint is used. In addition to humans, nearly all vertebrates suffer from osteoarthritis, including porpoises and whales, and long-extinct terrestrial travelers such as dinosaurs.

Joints

Joints are designed to provide flexibility, support, stability, and protection. These functions, essential for normal and painless movement, are primarily supplied by specific parts of the joint: the synovium and by cartilage, including collagen, its primary component.

The Synovium. The synovium is a membrane that surrounds the entire joint. It is filled with lubricating liquid, the synovial fluid , which supplies nutrients and oxygen to cartilage, one of the few tissues that does not have its own blood supply.

Cartilage. The cartilage is a slippery tissue that coats the ends of the bones. It contains a high percentage of water, 85% in young people to about 70% in older individuals. This high content is made possible by water-binding qualities of large molecules called proteoglycans, one of the primary building blocks of cartilage.

Collagen. Collagen, a major component of cartilage, forms a mesh to give support and flexibility to the joint. Collagen is the main protein found in all the connective tissues of the body, which include the muscles, ligaments, and tendons. The combination of the collagen meshwork and the high water content, tightly bound by proteoglycans, creates a resilient and slippery pad in the joint, which resists the compression between bones during muscle movement.

Osteoarthritis

Osteoarthritic Process. When cartilage in a joint deteriorates, osteoarthritis develops. The process is usually slow:

• In the early stages of the disease the surface of the cartilage becomes swollen, and there is a loss of proteoglycans and other tissue components. Fissures and pits appear in the cartilage. In some sufferers inflammation occurs around the synovium.
  
  
• As the disease progresses and more tissue is lost, the cartilage loses elasticity and becomes increasingly prone to damage due to repetitive use and injury.
  
  
• Eventually large amounts of cartilage are destroyed, leaving the ends of the bone within the joint unprotected.

Other problems occur as the body tries to repair damage:

• Clusters of damaged cells or fluid-filled cysts may form around the bony areas or near the fissures.
  
  
• Bone cells may respond to damage by multiplying and growing and by forming dense, misshapen plates around exposed areas.
  
  
• At the margins of the joint, the bone may produce outcroppings, on which new cartilage grows abnormally.

Location. Unlike some other types of arthritis, such as rheumatoid arthritis, osteoarthritis is not systemic: that is, it does not spread through the entire body. Rather, it concentrates in one or several joints where deterioration occurs. Osteoarthritis affects joints differently depending on their location in the body.

• It is commonly found in joints of the fingers, feet, knees, hips, and spine.
  
  
• It is rarely found in the wrist, elbows, shoulders, and jaw.

Fingers

Osteoarthritis of the fingers occurs most often in older women and may be inherited within families. It affects areas where bony knobs form in the joints, most commonly in the first joint below the tips (known as Heberden's nodes ) or less commonly in the next joint down ( Bouchard's nodes ). Gelatinous cysts, which sometimes go away on their own, may also form in the finger joints. Osteoarthritis also frequently damages the base of the thumb.

Knees

Osteoarthritis is particularly debilitating in the weight-bearing joints of the knees. Here, the joint is usually stable until the disease reaches an advanced stage, when the knee becomes enlarged and swollen. Although painful, the arthritic knee usually retains reasonable flexibility.

Hips

Osteoarthritis frequently strikes the weight-bearing joints in one or both hips. Pain develops slowly, usually in the groin and on the outside of the hips or sometimes in the buttocks. The pain also may radiate to the knee, confusing the diagnosis. Those with osteoarthritis of the hip often walk with a limp, because they slightly rotate the affected leg to avoid pain.

Spine

Osteoarthritis may affect the cartilage in the disks that form cushions between the bones of the spine, the moving joints of the spine itself, or both. Osteoarthritis in any of these locations can cause pain, muscle spasms, and diminished mobility. In some cases, the nerves may become pinched, which also produces pain. Advanced disease may result in numbness and muscle weakness. Osteoarthritis of the spine is most troublesome when it occurs in the lower back or in the neck, where it can cause difficulty in swallowing.

WHAT ARE THE SYMPTOMS OF OSTEOARTHRITIS?

The pain of osteoarthritis almost always begins gradually, progressing slowly over many years. People under 40 may have the condition with no symptoms at all. Osteoarthritis is commonly identified by the following symptoms:

• Aching pain in one or more joints, stiffness, and loss of mobility.
  
  
• Inflammation may or may not be present.
  
  
• Stiffness tends to follow periods of inactivity, such as sleep or sitting, and can be eased by stretching and exercise.
  
  
• The pain may behave like a roller coaster, with bad spells followed by periods of relative relief.
  
  
• Pain seems to increase in humid weather.
  
  
• It often worsens after extensive use of the joint and is more likely to occur at night than in the morning. As the disease advances, the pain may occur even when the joint is at rest and can keep a sufferer awake at night.
  
  
• Osteoarthritis in the knee may cause a crackling like noise (called crepitus) when moved.

WHAT OTHER CONDITIONS SHOW THE SAME SYMPTOMS AS OSTEOARTHRITIS?

It would be impossible to discuss in this report all the numerous conditions that have symptoms of joint aches and pains. Something as benign as sleeping on a bad mattress to the serious afflictions associated with cancer can mirror symptoms of osteoarthritis. Other problems that can cause aches and pains in the joints include physical injuries, infections, and poor circulation. A number of rare genetic diseases attack the joints.

Osteoarthritis can generally be distinguished from other joint diseases by considering a number of factors together: osteoarthritis usually occurs in older people and is located in only one or a few joints; the joints are less inflamed than in other arthritic conditions, and progression of pain is almost always gradual.

A few of the most common disorders that can be confused with, or may even accompany, osteoarthritis are worth noting.

Rheumatoid Arthritis

Osteoarthritis may be confused with rheumatoid arthritis, particularly when osteoarthritis affects multiple joints in the body. Rheumatoid arthritis begins in the synovial membrane rather than the cartilage. It normally occurs earlier in life than osteoarthritis, often striking people in their 30s and 40s. Many joints are affected, and rheumatoid arthritis often occurs symmetrically on both sides of the body. People generally have morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis usually clears up within half an hour.) X-rays show changes in the bones that differ from those occurring in osteoarthritis. In rheumatoid arthritis, blood tests often show a specific antibody, known as rheumatoid factor, that is not present with osteoarthritis. In another blood test, levels of a factor called erythrocyte sedimentation rate (ESR) are often elevated in rheumatoid arthritis, but they are generally normal in osteoarthritis. Rheumatoid arthritis also does not usually show up in the fingertips where osteoarthritis is common.

Chondrocalcinosis

Chondrocalcinosis is a disease in which certain calcium crystals known as CPPD (calcium pyrophosphate dihydrate) are deposited in the joints. It may affect 25% of the population and can accompany and even exacerbate osteoarthritis. The problem has been called pseudogout or pseudo-osteoarthritis, in the latter case particularly when it affects the knees. A physician can usually differentiate between the two disorders, however, because chondrocalcinosis usually damages other joints (such as wrists, elbows, and shoulders) that are not normally affected by osteoarthritis.

Charcot's Joints

Charcot's joint occurs when an underlying disease, usually diabetes, causes nerve damage in the joint, which leads to swelling, bleeding, increased temperature, and changes in bone. There may be a loss of sensation that leads to an increased risk for injury from overuse.

WHO GETS OSTEOARTHRITIS?

Aging

In the US, an estimated 6% of adults over 30 have osteoarthritis of the knee and about 3% have arthritis in the hip. When people age past 65, 85% show some evidence of osteoarthritis on x-ray, and about half experience symptoms. And as the population ages the prevalence of arthritic conditions is increasing.

Gender

Before age 45, osteoarthritis occurs more frequently in males (although it is not even common in younger adults). After age 55, it develops more often in females. In a 2000 study, 33% of women had osteoarthritis compared to 25% of men.

Education

The incidence is highest in lower educational levels. In a 2000 study, 41% of adults with less than a high school education had arthritis compared to 21% of college graduates.

Ethnicity and Inheritance

Osteoarthritis is common worldwide, although inherited forms of the disorder can influence age of onset, the location of affected joints, or both. The overall risk and the risk for its appearance in specific joints, then, vary among ethnic groups. The following are some examples:

• Asians appear to have a higher incidence of osteoarthritis in the knee than Caucasians do, an equal risk for osteoarthritis in the spine, and a lower risk for osteoarthritis in the hips. Because arthritis in the hip is so common, Caucasians have a higher risk in total than Asians.
  
  
• A 2000 study reported that in the US, older African American men are about 33% more likely than white men to have hip osteoarthritis. And, although men in both groups had equal risks for arthritic knees, African American men were more likely to have it in both knees and to have more severe cases. Although comparable disparities in knee arthritis were observed between African American and Caucasian women, they might be explained by greater average weight among African American women. The study could not account for the differences among men, however.

Obesity

Obesity, which is defined as being 20% over one's healthy weight, places people (particularly women) at increased risk for osteoarthritis, most likely because of increased weight on the joints. In one study, overweight women also tended to have less muscle strength in their legs, which could contribute to their risk. (Muscular strength did not seem to be impaired in overweight men.)

Work Factors

A 2000 study suggested that workers whose jobs require kneeling or squatting for more than an hour a day are at high risk for knee osteoarthritis. (In the study, jobs that involved heaving lifting, climbing stairs, or walking also posed some, but not as high a risk. Being heavier compounded the chances for osteoarthritis.

WHAT CAUSES OSTEOARTHRITIS?

Although osteoarthritis generally accompanies aging, osteoarthritic cartilage is chemically different from normal aged cartilage. Many experts now believe that osteoarthritis is a disorder that results from a genetic susceptibility coupled with injuries to the joint.

Genetic and Biologic Factors

Researchers report a higher correlation of osteoarthritis between parents and children or between siblings than between husbands and wives. Genetic factors are thought to be involved in about half of osteoarthritis cases in the hands and hips and a somewhat lower percentage of cases in the knee. A number of genes are under investigation that might contribute to an inherited risk.

• A 2000 study identified the ank gene, which regulates pyrophosphate, a chemical that inhibits the formation of mineral deposits, and may protect the cartilage in joints. (Pyrophospate is also a substance used in tartar control toothpaste). About 60% of persons with osteoarthritis have mineral deposits in their cartilage. Researchers in the study suggested that mutations in the ank gene that may result in lower pyrophosphate levels in the joint, leading to accumulation of mineral deposits and arthritis.
  
  
• The newly detected osteoprotegerin gene is important in regulating bone and cartilage formation. Mutations in this gene may play a in role in osteoarthritis.

Muscle Weakness

It is commonly thought that osteoarthritis results in disuse in the muscles of the leg, causing them to weaken and atrophy. Of interest is a study that reverses this thinking. It suggested that weak muscle tissue in the quadriceps is responsible for osteoarthritis in the first place. (The quadriceps are four muscles that stretch down the thigh and attach to the knee and are responsible for leg extension.) This weakness may be due to an abnormality in the muscles themselves or in the nerves that serve those muscles. In the study, strength tests revealed that people with osteoarthritis had muscle weakness in the quadriceps even if they had no pain. There was no difference in signs of muscle atrophy (withering) between the legs of arthritic patients and those of nonarthritic people.

Anatomical Factors

Some researchers suggest that a number of people have anatomical abnormalities, such as mismatched surfaces on the joints, which could be damaged over time by abnormal stress. Legs of unequal length or skewed feet can cause jerky movement and may induce osteoarthritis. In a study on hand grip strength, for example, individuals, particularly men, whose grip was very powerful were at increased risk of developing osteoarthritis in certain hand joints over time.

Injuries

Injury from different sources can contribute to osteoarthritis:

Single Injury. Osteoarthritis sometimes develops after a single traumatic injury to or near a joint.

Repetitive Labor. Certain occupations that require repeated stressful motions (such as squatting or kneeling with heavy lifting) can also contribute to deterioration of cartilage.

High-Intensity Exercise. There has been some question about the role of strenuous exercise in osteoarthritis. Marathon runners, for instance, have a relatively low rate of osteoarthritis in general. One study that did report a higher rate of osteoarthritis in marathon runners compared to other athletes associated it with intensity of impact rather than with the distance being run. Other scientists, however, speculate that running enhances cartilage health because the rhythmical compression of cartilage expels wastes and promotes absorption of nutrients. Sports that definitely pose a higher risk for osteoarthritis are those that require repetitive or direct joint impact (such as football), twisting, or both (baseball, soccer). It should be noted however, that muscle weakness and low lung capacity are associated with a high risk for osteoarthritis and non-traumatic exercise is strongly recommended for healthy people.

Obesity

Being overweight exacerbates osteoarthritis once deterioration begins. One major long-term study suggested there may be a causal relationship between obesity in women and osteoarthritis of the knees. In men, the association is not as strong.

WHAT TESTS WILL CONFIRM THE DIAGNOSIS OF OSTEOARTHRITIS?

X-Rays

Osteoarthritis is often visible on x-rays. Cartilage loss is indicated by certain images:

• If the normal space between the bones in a joint is narrowed.
  
  
• If there is an abnormal increase in bone density.
  
  
• If bony projections or erosions are evident.

X-rays can also reveal any cysts that might develop in osteoarthritic joints. If other conditions are suspected or if the diagnosis is uncertain, additional tests will be performed.

Blood Tests

Blood test results may help diagnose or rule out osteoarthritis. Some examples include the following:

• Elevated levels of rheumatoid factor (specific antibodies in the synovium) and so-called erythrocyte sedimentation rates (ESR or sed rate) indicate rheumatoid arthritis.
  
  
• Byproducts of hyaluronic acid, a joint lubricant, may prove to be markers of the lubricant's breakdown and an indicator of osteoarthritis.
  
  
• Elevated levels of a factor called C-reactive protein, which is produced by the liver in response to inflammation, are proving to be good predictors of osteoarthritic progression in the knee.

Tests of the Synovial Fluid

If the diagnosis is uncertain or infection is suspected, the physician may attempt to withdraw synovial fluid from the joint using a needle. If the joint is normal, there is not enough fluid to withdraw. It there is, then problems are likely and the fluid is tested for factors that might confirm or rule out osteoarthritis:

• Cartilage cells in the fluid are signs of osteoarthritis.
  
  
• A high white blood cell count is a sign of infection.
  
  
• High uric acid in the fluid is an indication of gout.
  
  
• Other factors may be present that suggest different arthritic conditions, including Lyme disease and rheumatoid arthritis.
  
  
• In people with known ostearthritis, researchers are looking at certain factors in synovial fluid (eg, sulfated glycosaminoglycan, keratan sulfate, and link protein) that may predict severity.

HOW SERIOUS IS OSTEOARTHRITIS?

Osteoarthritis itself is not life threatening, but the quality of life can significantly deteriorate from pain and loss of mobility. The negative effects on activities and physical and mental health are significant regardless of age, educational level, or gender. Only heart disease has a greater impact on work. Five percent of those who leave the work force do so because of osteoarthritis. Unless alleviated by medication or corrected by surgery, advanced osteoarthritis can force the patient to forgo even relatively low-impact activities, such as walking. No treatment can cure osteoarthritis, and none can alter its progression with certainty, although many therapies are available that can relieve symptoms and significantly improve the quality of life.

WHAT ARE LIFESTYLE MEASURES FOR MANAGING OSTEOARTHRITIS?

Many physicians suggest first trying lifestyle changes to reduce stress on affected joints. Physical therapy and supportive devices can be helpful. Intensive education on how to protect and care for an osteoarthritic joint may help the patient avoid multiple visits to their doctor and translate into substantial long-term savings.

Occupational Changes

Once osteoarthritis has been diagnosed, patients should reduce shock to the affected joint. Hammering away at deteriorating cartilage is likely to speed up the degeneration. People in occupations requiring repetitive and stressful movement should explore ways to reduce trauma. Adjusting the work area or substituting tasks that produce less stress on joints help reduce shock.

Exercise

Exercise has some obvious benefits for osteoarthritic patients and may delay the need for pain relievers:

• In general, exercise helps to reduce pain and stiffness, and increases flexibility, muscle strength, endurance, and a sense of well being.
  
  
• Joints require motion to stay healthy. Long periods of inactivity cause the joint to stiffen and the adjoining tissue to atrophy.
  
  
• Exercising also helps people reduce weight and maintain weight loss.

Although strong evidence for the benefits of exercise on osteoarthritis is lacking, an analysis of clinical trials indicated that exercise for the hip or knee could benefit some patients. One study reported that patients who embarked on an aerobic and resistance exercise program had less disability, pain, and better ability to perform physical tasks than a group that received patient education only. Patients should strive for short but frequent exercise sessions guided by physical therapists or certified instructors. Older patients and those with medical problems should always check with the physician before embarking on an exercise program.

Exercising Tips for Osteoarthritic Patients. The three types of exercise that are best for people with arthritis are range of motion exercises, strengthening exercises, and aerobic, or endurance, exercises.

• Strengthening exercises include isometric exercises (pushing or pulling against static resistance). Isometric training builds muscle strength while burning fat, helps maintain bone density, and improves digestion. Strengthening the thigh muscles is certainly protective. According to experts, even a modest increase in strength (20% for men and 25% for women) can reduce the risk for osteoarthritis by 20% to 30%. Some experts encourage patients to emphasize strengthening leg muscles as a first treatment step, even before using pain relievers. They fear that patients who rely on pain killing drugs may overuse knees, which do not have muscle tissue sufficiently strong enough to protect the joints from further damage.
  
  
• Range-of-motion exercises increase the amount of movement in a joint and muscle. In general, they are stretching exercises. The best examples are Yoga and Tai Chi, which focus on flexibility, balance, and proper breathing. They also lower stress levels, help to reduce blood pressure, and may even have beneficial effects on cholesterol levels.
  
  
• Aerobic or endurance exercises are also important for the heart, help control weight, and improve overall function. They may even reduce inflammation in some joints. Low-impact workouts also help stabilize and support the joint. (Arthritic patients should avoid high-impact sports, such as jogging, tennis, and racquetball.) Cycling and walking are beneficial, and swimming or exercising in water is highly recommended for people with arthritis.

Physical Therapy

In addition to exercise, manipulation of muscles and joints by a trained therapist may be helpful. In one 2000 study, patients who had a combination of this therapy and an exercise program reported that they felt 30% to 40% better after only two to four visits. Such a program may also reduce the need for operations.

Weight Reduction

Overweight osteoarthritis patients can lessen the shock on their joints by losing weight. Knees, for example, sustain an impact three to five times the body weight when descending stairs. Consequently, a modest loss of five pounds can eliminate at least 15 pounds of stressful impact on the joint. The greater the weight loss, the greater the benefit. [For more information, see the Report #53, Obesity and Weight Loss .]

Estrogen and Hormone Replacement Therapy

Hormone replacement therapy (HRT), which is either estrogen alone or estrogen plus progestin, is known to protect postmenopausal women against osteoporosis, a disorder that causes bones to become porous. Studies on its effects on ostearthritis, however, have been mixed. A major 2001 study on the effects of hormone replacement therapy reported no effect on osteoarthritis in the knee after four years. (More significantly, in July 2001, the American Heart Association sent out an advisory stating that women with heart disease, or women who have a heart attack while on HRT, should stop the therapy. In addition, they recommend that doctors stop telling women that hormone replacement therapy has any cardiovascular benefits.)

Vitamins and Dietary Factors

Plant Chemicals. A multicenter study in France reported significant symptomatic improvement in patients who took extracts from avocados and soybeans called saponins compared with patients who took a placebo. More research is needed on these nutrients.

Vitamins. Vitamin C may have some protective benefits. It should be strongly stressed that for full health benefits, vitamins and other important nutrients work best as a team and should be obtained in a diet that is rich in fresh fruits and vegetables.

Vitamin B3 (Niacin). Some research suggests that vitamin B3 may have some benefits for people with osteoarthritis.

Calcium and Vitamin D. Calcium and vitamin D are important for strong bones. It should be noted, however, that while denser bones are protective against fractures due to osteoporosis, the problems in osteoarthritis are in the joints not the bones. Still, calcium is important, particularly in older people.

• Many experts are now recommending 1000 mg of calcium a day for most adults and 1,200 to 1,500 mg for adolescents. Pregnant women, postmenopausal women not on estrogen therapy, and those on corticosteroids should have 1500 mg per day; breast feeding women should have 2000 mg/day. Because calcium supplements increase the risk for kidney stones, an upper limit of 2,500 mg is recommended.
  
  
• Current guidelines recommend 400 IU of vitamin D per day and 600 IU per day above age 61. Lack of sunlight and unhealthy diets contribute to deficiencies in vitamin D. Good dietary sources include fortified milk, sardines, herring, salmon, tuna, liver, dairy products, and egg yolks. Although supplements are often necessary, vitamin D can be toxic in high doses, and no one should take more than 1200 IU per day.

Heat and Ice

Ice. When a joint is inflamed (particularly in the knee) applying ice for 20 to 30 minutes can be effective. (If an ice pack is not available, a package of frozen vegetables works just as well.)

Heat Treatments. Patients afflicted with osteoarthritis of the hands can relieve pain with hot soaks and warm paraffin application. Osteoarthritis of the hip can be treated with heating pads.

Warm Climates. Interestingly, moving to a warm climate does not seem to make much difference. According to one study, people who live in warmer places are actually more sensitive to small shifts in temperature than people who live in cold damp climates, and they experience pain as readily as their northern peers do in response to larger temperature shifts.

Mechanical Aids

A wide variety of devices are available to help support and protect joints:

• Wearing shock-absorbing soles in shoes or orthopedic shoes can help in daily activities and during gentle exercise. Heel wedges in the shoes can even sometimes help patients avoid knee replacement surgery.
  
  
• Splints or braces, worn while the joint is at rest or in use, help align joints and properly distribute weight. They are used most frequently to treat arthritic hands, wrists, knees, ankles, and feet. Many such devices allow some movement within the affected joint and do not restrict nearby joints. They are usually made from lightweight metal, leather, elastic, foam, and moldable plastic with easy-to-use Velcro straps. Any brace, splint, or other device for joint protection should be custom-fitted by a physical or occupational therapist, or an orthotist. Poorly fitting or improperly used orthoses can cause more harm than good. Some insurance companies cover 80% of the expense.
  
  
• Affected knee and wrist joints benefit from over-the-counter elastic supports, but it is important to check with a physician before using one.
  
  
• A neck brace or corset may relieve back pain.
  
  
• A firm mattress also often proves beneficial.
  
  
• In extreme cases of back pain, lying in traction might be necessary.
  
  
• Canes, crutches, or walkers offer benefits to patients with advanced arthritis.

WHAT ARE THE MEDICATIONS USED FOR OSTEOARTHRITIS?

Because osteoarthritis is most likely not caused by inflammatory factors (as rheumatoid arthritis is), mild conditions usually respond to acetaminophen and more severe cases usually respond to nonsteroidal anti-inflammatory drugs (NSAIDs). The American Geriatrics Society recommends that patients with osteoarthritis first try acetaminophen. Many osteoarthritis patients report better pain relief from NSAIDs than from acetaminophen, but prolonged use of NSAIDs can have severe side effects, particularly gastrointestinal bleeding.

Acetaminophen

The American College of Rheumatology now recommends acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol, and others) as the first choice for mild to moderate osteoarthritic pain. An estimated 20% to 30% of patients achieve satisfactory results with acetaminophen, which can be used alone or in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). One acetaminophen product, Tylenol Extended Relief, is a controlled-release medication that needs to be taken only every eight hours and can help people achieve uninterrupted sleep without additional sleeping aids. Acetaminophen has its own risks, however. One study reported that up to 5,000 cases of kidney failure every year may be attributed to heavy use of acetaminophen and that taking just one pill a day for a year can double the risk of kidney disease. Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Common NSAIDs. The most common pain-relievers are the nonsteroidal anti-inflammatory drugs (NSAIDs). They are now recommended for moderate to severe osteoarthritis pain if acetominphen fails to relieve symptoms. These agents block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs. Some of the most common are aspirin, ibuprofen, naproxen, and ketoprofen, but many others are available.

Side Effects and Complications. Regular use of even over-the-counter NSAIDs may be hazardous for anyone and has been associated with the following side effects:

• Ulcers and gastrointestinal bleeding. This is the major danger with long-term use of NSAIDs. [ See Box Ulcers and Gastrointestinal Bleeding.] Taking NSAIDs with food can reduce stomach discomfort, although it may slow down the pain-relieving effect.
  
  
• Increased blood pressure. This is a particular problem in those on medications to reduce hypertension. Piroxicam (Feldene), naproxen (Aleve), and indomethacin (Indocin) appear to pose the greatest risks for high blood pressure. (Sulindac has the smallest effect.) People with hypertension, severe vascular disease, kidney, or liver problems, and those taking diuretics must be closely monitored if they need to take NSAIDs.
  
  
• May delay the emptying of the stomach, which could interfere with the actions of other drugs. The elderly are at special risk.
  
  
• Dizziness, ringing in the ear.
  
  
• Headache.
  
  
• Skin rash.
  
  
• Depression has also been noted.
  
  
• Confusion or bizarre sensation (in some higher-potency NSAIDs, such as indomethacin).
  
  
• Kidney abnormalities have been reported in people taking NSAIDs, which resolves when the drugs are withdrawn. Any sudden weight gain or swelling should be reported to a physician.
  
  
• Diabetics taking oral hypoglycemics may need to adjust the dosage if they also need to take NSAIDs because of possible harmful interactions between the drugs.

NSAID-Induced Ulcers and Gastrointestinal Bleeding NSAIDs are a major cause of ulcers and gastrointestinal (GI) bleeding. Gastrointestinal complications from the use of NSAIDs account for almost 100,000 hospitalizations and at least 16,000 deaths a year in the United States. Bleeding and ulcers can occur at any time, with or without symptoms. One study indicated that taking NSAIDs for only six months posed a risk for symptomatic ulcers that was greater than 1%. The risk for bleeding is continuous as long as a patient is on these drugs and may even persist as long as a year after the drug is discontinued. Alcohol abuse may increase the risks for GI bleeding when taking NSAIDs. Because NSAIDs reduce the clotting of the blood, anyone undergoing surgery should stop taking the medication a week before the operation. Ulcer Risk for Specific NSAIDs. One study ranked the sixteen most commonly used NSAIDs according to risk for ulcers and bleeding. Lowest Risk: nabumetone (Relafen), etodolac (Lodine), salsalate, and sulindac (Clinoril). Medium risk: diclofenac (Voltaren), ibuprofen (Motrin, Advil, Nuprin, Rufen), aspirin, naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and tolmetin (Tolectin). (Drugs within this group vary in risk. Studies show, for example, that short-term use of naproxen is twice as likely as ibuprofen to be associated with hospitalization from GI bleeding. Although ketoprofen (Actron, Orudis KT) was considered a medium-risk drug, another study reported that even one week of taking the drug at low doses causes significant GI injury. Highest risk: flurbiprofen (Ansaid), piroxicam (Feldene), fenoprofen, indomethacin (Indocin), meclofenamate (Meclomen), and oxaprozin. Drugs for Prevention of NSAID-Induced Ulcers. For people who need to take NSAIDs regularly, some agents are available that may protect against bleeding and ulcers. Proton-pump inhibitors a include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprozole. Proton pump inhibitors are possibly the most protective agents and can actually heal existing ulcers. Their use has been demonstrated to reduce NSAID-ulcer rates by as much as 80% compared with no treatment. Misoprostol. Misoprostol is a prostaglandin, the protective substance blocked by NSAID use. It protects against the major intestinal toxicity of NSAIDs. It is used to prevent NSAID-induced ulcers, both duodenal and gastric, but is not useful in healing existing ulcers. H2 Blockers. Some H2 blockers may help prevent NSAID-induced ulcers. These drugs are available over the counter and include famotidine (Pepcid AC), ranitidine (Zantac), cimetidine (Tagamet), and nizatidine (Axid). In one 2000 study, ranitidine and famotidine were associated with a lower risk for bleeding in patients taking NSAIDs, but another study found no protection from cimetidine.

COX-2 Inhibitors

Celecoxib (Celebrex), rofecoxib (Vioxx), and meloxicam (Mobic) are known as COX-2 (cyclooxygenase-2) inhibitors, the so-called super-aspirins. The drugs are all equally effective in relieving pain, although few comparative studies have been conducted.

Benefits. These agents have the following benefits:

• They may prove to be as effective and less harmful to the GI tract than NSAIDs. Importantly, studies are reporting a lower incidence of ulcers and other toxic side effects in patients taking the COX-2 inhibitors than in those taking NSAIDs. One 1999 study even found the rate of GI problems with celecoxib was equal to that in people who do not take NSAIDs at all.
  
  
• Theoretically, they may even have properties that produce less adverse effects on cartilage than NSAIDs may have.
  
  
• Some early evidence also suggests that, like NSAIDs, they may be partially protective against colon cancer and possibly even Alzheimer's disease.

COX-2 inhibitors are currently more expensive than traditional NSAIDs, however, and some insurers do not pay for them.

Possible Negative Effects. In spite of their promise, some researchers theorize that inhibiting COX-2 may have some negative side effects over the long term:

• Although COX-2 inhibitors are very likely to have a lower risk for ulcers and GI bleeding than standard NSAIDs, studies have been mixed on whether patients taking COX-2 inhibitors have the same gastrointestinal symptoms (eg, diarrhea, abdominal discomfort) as standard NSAIDs. Vioxx may pose a higher risk for symptoms than Celebrex. (Other side effects found with short-term use include headache, and dizziness.)
  
  
• One 2000 study observed that the COX-2 inhibitors had some adverse effects on kidney function, particularly in elderly people, that were similar to the effects of standard NSAIDs. This effect can also trigger fluid build up and high blood pressure. (Celebrex may have fewer of these effects than Vioxx.)
  
  
• Patients taking anticoagulant drugs may experience a higher risk for bleeding with the use of these agents.
  
  
• A 2001 study reported a higher incidence of heart attacks in patients taking Vioxx than in those taking a standard NSAID, naproxen. Some evidence suggests that both COX-2 inhibitors may increase the risk for blood clots. Experts also suggest that heart patients with chronic pain may be substituting COX-2 inhibitors for heart-protective NSAIDs (such as aspirin, ibuprofen, or possibly naproxyn). Patients with heart disease who are taking low-dose aspirin should continue it even while they are taking COX-2 inhibitors.
  
  
• A few cases of psychiatric side effects (hallucinations), fluid build up, high blood pressure, and excess potassium in the blood have been observed with higher doses of celecoxib or rofecoxib.
  
  
• They may have negative effects on pregnancy and fertility.
  
  
• People who have experienced allergic reactions (asthma or hives) from sulfa drugs, aspirin, or other NSAIDs, should not take COX-2 inhibitors.
  
  
• The use of COX-2 inhibitors can interfere with many other drugs taken concurrently, including many taken for heart disease and high blood pressure. Patients should discuss all other medications with their physician.

More research is needed to confirm or refute any possible hazard.

Capsaicin

Capsaicin is a component of hot red peppers and may bring pain relief when used as a skin cream (Zostrix). This is the only skin preparation that does more than just mask pain or reduce it temporarily. Capsaicin seems to reduce a substance in the body, known as substance P, which contributes both to inflammation and the delivery of pain impulses from the central nervous system. A small amount of capsaicin must be applied to the area of inflammation about four times a day. During the first few days of use, the patient will experience a warm, stinging sensation when the cream is applied. This sensation goes away, and pain relief usually begins within one to two weeks.

Narcotics

Narcotics, pain-relieving and sleep-inducing drugs that act on the central nervous system, are the most powerful medications available for the management of moderate to severe pain. There are two types of narcotics:

• Opiates which are derived from natural opium (eg, morphine and codeine).
  
  
• Opioids, which are synthetic drugs (eg, oxycodone, tramadol).

Controlled-release tramadol (Ultram) is proving to be particularly effective for treating moderate to severe osteoarthritic pain and has relatively few side effects. It has specific properties that make dependency unlikely and it can be used in combination with NSAIDs. Of great concern are media reports of abuse from illegal sales of oxycodone (Percodan, Percocet, Roxicodone, Oxycontin), a very effective pain killer. Such reports may cause unwarranted fear of addiction in chronic pain sufferers who might benefit from tramadol.

Although the use of narcotics for arthritic pain is controversial, many studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse. Some experts, then, believe that opioids have a place in osteoarthritis treatment when milder drugs are not effective or appropriate. The use of such agents is very beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects.

Corticosteroids

When pain becomes a major problem and less potent pain relievers are ineffective, physicians may resort to corticosteroid (steroid) injections, usually by administering a shot into the affected joint every three months. No more than two or three injections a year should be administered. Corticosteroid shots are useful only if inflammation is present in the joint. Relief from pain and inflammation is of short duration, and this treatment is rarely used for chronic osteoarthritis. Corticosteroids mask pain and the patient must be very careful to avoid over-use of the affected joints. Because long-term use of corticosteroids has many potentially serious side effects, steroid medications are never given orally or systemically for the treatment of osteoarthritis.

Experimental Therapies

NO-NSAIDS. Experimental agents are being developed that combine nitric oxide with NSAIDs (NO-NSAIDs). Nitric oxide increases blood flow in the mucous lining and secretions of mucus and bicarbonate. Combining nitric oxide with NSAIDs may provide benefits similar to the COX-2 inhibitors.

Tetracycline Antibiotics. Laboratory research suggests that certain tetracycline antibiotics, such as doxycycline, may have a role to play in treating osteoarthritis. Laboratory studies are reporting that, at low concentrations, the drug reduces the production of collagenases, which are enzymes critical to disease development and progression. Human trials are needed to confirm these findings.

WHAT ARE ALTERNATIVE TREATMENTS BEING USED FOR OSTEOARTHRITIS?

Glucosamine and Chondroitin Sulfate

Glucosamine and chondroitin sulfate are natural substances found in and around cartilage. Extracts from animal products have been used in Europe for more than a decade to reduce pain and improve mobility in patients with osteoarthritis. Both substances may possibly play a role in cartilage repair and maintenance. These agents may be taken together, and, in fact, some studies report that they are more effective when taken together than when taken alone. Studies to date report the following:

Glucosamine Sulfate. Studies in 2000 and 2001 reported that glucosamine sulfate slowed or even prevented progression of joint changes that cause osteoarthritis. A major 2001 analysis of studies reported that glucosamine sulfate was safe and effective for osteoarthritis. In four of the studies it was equal or superior to NSAIDs. (One 2001 study theorized that sulfate may be important in the effectiveness of glucosamine and nonsulfate salts may not have any benefits.)

Chondroitin Sulfate. A review of seven European trials involving chondroitin sulfate indicated that pain scores dropped by about 60% with chondroitin versus only about 20% from placebo. A well-controlled 2001 study observed a beneficial trend after three months of treatment.

Side Effects. Although at this time few adverse side effects have been reported, long-term effects are still unknown. A major US trial is underway to determine both risks and benefits. It should be noted that a preliminary study suggests that glucosamine reduces the metabolic action of insulin, which would be of great concern among diabetic and obese individuals. No one should take either or both agents without seeking medical advice. Potential users need to be aware that glucosamine and chondroitin products are not regulated by the FDA. An analysis of commonly available brands, however, suggests that major drugstore brands (CVS, Walgreens, Wal-Mart) of combination products are manufactured with appropriate ingredients.

Viscosupplementation

Viscosupplementation is the injection of hyaluronic acid (Hyalgan, Synvisc) into the joint and is now recommended as one of the treatments for osteoarthritis. Hyaluronic acid is a naturally occurring substance in joints that acts as a lubricant for slow movements and a shock absorber for fast motions:

• The agent is administered by injection into the joint.
  
  
• Patients receive a series of three (Synvisc) to five (Hyalgan) injections given once a week.
  
  
• Because these products are viscous (sticky), administration requires a large needle, so a local anesthetic is applied.
  
  
• Patients are told to avoid weight-bearing activities for about 48 hours after each injection.

Viscosupplementation is now approved by the FDA and the American College of Rheumatology. Hyalgan and Synvisc appear to be about as effective as NSAIDs for relieving pain, and they have no adverse effects in the stomach or intestines. Benefits last for about six months. Some studies on Synvisc are suggesting that it significantly reduces pain and improves quality of life. One study on Synvisc reported that between 39% and 56% of patients were at least nearly free of weight-bearing pain 10 to 24 weeks after the final injection. And in another study, response was judged better or much better for 87% of knees after a second course, which was administered about eight months later. Nevertheless, a number of studies on viscosupplementation have shown only small benefits and more work is needed. Injections are also expensive.

Side Effects. Serious adverse reactions are rare, and the most common side effects, pain at the injection site and knee pain and swelling, are usually mild and temporary. More research is needed to confirm their benefits and long-term risks.

Other Investigative Alternative Substances

Oral Enzymes. Oral agents containing various natural enzymes, including bromelain, trypsin, papain, and rutin, have been used overseas to treat arthritic pain. Such enzyme combinations (Wobenzym, Phlogenzym) may reduce inflammation and cartilage damage. They are not pain killers; any benefits derived from them may take several weeks. Animal studies and small trials supported by the manufacturer have reported benefits, but there have been very few well-conducted human trials. Some are now underway.

S-adenosylmethionine (SAMe). S-adenosylmethionine (SAMe, pronounced "Sammy") is a synthetic form of a natural byproduct of the amino acid methionine. It has been marketed as a remedy for both depression and arthritis. Few side effects have been reported from SAMe in clinical trials, and the existing research suggests that it may be an effective short-term treatment for osteoarthritis. Some research suggests that it may even rebuild damaged cartilage. Better-designed studies are needed, however, before its true effectiveness and long-term safety can be determined. According to an analysis of current brands, reliable SAMe products include GNC, Natrol, Nature Made, The Vitamin Shoppe, Twin Laboratories, Source Naturals, NutraLife Health Products, and Puritan's Pride.

Warnings on Alternative and So-Called Natural Remedies It should be strongly noted that alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. Even if studies report positive benefits from herbal remedies, the compounds used in such studies are, in most cases, not what are being marketed to the public. There have been a number of reported cases of serious and even lethal side effects from herbal products. In addition, some so-called natural remedies were found to contain standard prescription medication. Most problems reported occur in herbal remedies imported from Asia, with one study reporting a significant percentage of such remedies containing toxic metals. Of note for patients with osteoarthritis, chondroitin sulfate and glucosamine are now available in many standard brands. Ratings on various brands are available on the following website (http://www.ConsumerLab.com/). This excellent site is building a database of natural remedy brands that it tests and rates. The Food and Drug Administration has a program called MEDWATCH for people to report adverse reactions to untested substances, such as herbal remedies and vitamins (call 800-332-1088).

Acupuncture

Acupuncture has been tried in a few medical clinics to reduce osteoarthritis pain with some success. The technique is painless and involves the insertion of small fine needles at different points in the body. Large scale trials are still lacking, but evidence on its benefits is fairly strong, and it may be a safe and beneficial addition to standard therapy for certain patients.

Transcutaneous Electric Nerve Stimulation

Transcutaneous electric nerve stimulation (TENS) uses low-level electrical pulses to suppress pain. The patients are barely aware of the sensation. A variant (sometimes called percutaneous electrical nerve stimulation or PENS) applies these pulses through a small needle to acupuncture points. A 2001 analysis of seven trials reported that both methods were better than placebo (sham treatments) in treating osteoarthritis of the knee, although additional well-designed studies are needed.

Hydrotherapy

Hydrotherapy, also called spa therapy or balneotherapy, is an ancient therapy that uses bathing in mineral baths for soothing pain. Although many studies report positive results, including quality of life, very few have been rigorously conducted. A major analysis reports that evidence is very weak on any real effect on pain or quality of life, but some experts say that one should not ignore the benefits reported by patients from such pleasant therapy.

Cognitive Behavioral Therapy

Some researchers have reported that cognitive-behavioral therapy (CBT) combined with exercise can be effective for managing the chronic pain of osteoarthritis. The primary goal of cognitive therapy in cases of pain-management is training in relaxation and methods for changing the patient's approach to their pain. Using specific tasks and self-observation, patients gradually shift their fixed ideas that they are helpless against the pain that dominates their lives to the perception that pain is only one negative and, to a degree, a manageable experience among many positive ones.

WHAT ARE THE SURGICAL TREATMENTS FOR OSTEOARTHRITIS?

Different surgical procedures are available as a final measure to relieve pain and increase function in osteoarthritis patients. Certain surgical procedures might relieve pain if medications fail. Even with these procedures, however, joint replacement may still be needed later on.

Arthroscopy

Arthroscopy is performed to clean out bone and cartilage fragments that cause pain and inflammation. It is usually performed on the knee but it also may be done on the hip:

• The surgeon makes a small incision and injects a sterile solution to make the joint swell for easier viewing.
  
  
• Then a lighted tube, called an arthroscope (which enables the surgeon to view the joint), is inserted through another small incision.
  
  
• Through a third incision the surgeon trims, shaves, or stitches the damaged tissue. (Arthroscopy is most successful when the removal of cartilage only, and not bone, is involved.)

In many cases, the procedure can be done using local anesthetic and the patient can go home within a day. In the case of knee operations, patients can resume mild activity in a couple of days, but full recovery can take up to three months.

Joint Replacement (Arthroplasty)

When osteoarthritis becomes so severe that pain and immobility make normal functioning impossible, many people become candidates for artificial (prosthetic) joint implants using a procedure called arthroplasty. Hip replacement is the most established and successful replacement procedure, followed by knee replacement. Knee replacement, in fact, has a slightly better long-term success rate than hip replacement. Other joint surgeries (shoulders, elbows, wrists, fingers) are less common, and some arthritic joints (in the spine, for instance) cannot yet be treated in this manner.

Candidates. The primary indications for surgery are pain and significant limitations of movement, including walking, that cannot be treated by less invasive therapies. Patients who may not be good candidates are those with the following conditions:

• Severe neurologic, emotional, or mental disorders.
  
  
• Severe osteoporosis.
  
  
• Other chronic medical conditions.
  
  
• Obesity.

Surgeons often prefer to delay prosthetic implantation in relatively young patients in order to reduce the likelihood of repeat surgery later on. Of concern, however, are other patient groups who might be good candidates but are not receiving treatment:

• Although women have a higher prevalence of osteoarthritis of the hip and knee and worse symptoms, they are three times less likely to have arthroplasty than men are. The reasons for this are not entirely clear.
  
  
• Evidence suggests that the procedure is performed less often among African Americans. (Furthermore, the risk for arthritic knees is higher in African Americans, particularly women.)
  
  
• One 1999 study suggested that healthy people in their 90s can derive significant benefits from arthroplasty (although they are at higher risk for complications related to other medical problems).

Procedure Description. Although only hip replacement surgery is described in this report, the principles are similar for other arthroplasties. A typical procedure follows:

The surgeon removes the ball and socket joint that joins the pelvis and thigh bone (femur) and replaces it with an artificial joint (a prosthesis). The prosthesis is composed of two pieces:

• A cup-like device fits in the hip socket (called the acetabula), which has been hollowed out. This ball-and-socket cup is positioned to form the new joint.
  
  
• A metal shaft, or stem, with a polished metal ball at the top, is inserted into the narrow center of the femur.

The prosthesis is usually made of a chromium alloy and plastic. There are different options available for attaching it to the adjoining bones:

• A cement made of polymethylmethacrylate (usually preferred for older patients who generally have thinner bones).
  
  
• So-called cementless implants, in which the prosthesis is coated with a porous material that allows bone to grow into and eventually adhere to the device (usually used for patients under 65, who are likely to need repeat surgery in their lifetime).

Complications. Complications include the following:

• The risk for deep blood clots (known as deep vein thrombosis) is very high without anticoagulant therapy, which typically includes either warfarin or enoxaparin (a drug known as low-molecular weight heparin or LMWH). LMWH is more effective in preventing deep blood clots from forming but has a higher risk for bleeding than warfarin. The anticoagulant hirudin (desirudin) is proving to be another effective alternative. The patient also typically wears specially fitted elastic stockings to help prevent clots. Patients who are overweight are at higher than average risk for post-operative blood clots.
  
  
• Infection occurs in 1% of joint replacements and requires removal of the implant to treat the infection. A new prosthesis must then be re-implanted at a later time. Any pre-existing infection must be treated and cured before surgery is performed. (Older women should be aware of urinary tract infection symptoms, which may be a strong indicator for postponing surgery.) After surgery, patients should take certain precautions. For example, they should take antibiotics before invasive dental procedures or any other surgery. In such cases, bacteria may be introduced into the bloodstream and infect the areas around the artifical joints.
  
  
• Hip dislocation occurs in between 1% and 5% of all cases of hip procedures.
  
  
• Thigh pain can occur after either hip replacement. For reasons still unclear, porous hip prostheses are more apt to produce thigh pain than cement implants, although advanced techniques using a tapered shaft are reducing this complication.
  
  
• The primary reason for implant failure is osteolysis (bone destruction) caused by long-term wear. The main source of wear is from tiny particles released from the prosthesis.
  
  
• Other complications include uneven leg lengths, nerve damage that can cause numbness or weakness, urinary tract infections, delayed healing, and allergic reactions to the metal. There have been rare reports of a possible autoimmune response after long-term use. This response is a reaction by the immune system, in which certain immune factors are tricked by loose particles released from the prosthetic device into attacking its own cells. Any incidence of unexplained weight loss and fatigue may be symptoms of this uncommon event.

Rehabilitation. Aside from the surgeon's skill and the patient's underlying condition, the success rate depends on the kind and degree of activity the joint receives following replacement surgery.

• The patient is urged and aided into getting out of bed and walking the day after surgery.
  
  
• Most hip replacement patients leave the hospital within a week and can walk with crutches within two to four weeks, recovering fully in about three months.
  
  
• Physical therapy itself takes about six weeks to rebuild adjoining muscle and strengthen surrounding ligaments.

Limitations After Surgery. While many patients find that joint replacement provides remarkable pain relief and restores some mobility, they need time to adjust to the artificial joint, and there are some limitations.

Limitations after hip surgery include the following:

• Usually patients with new hips are able to walk several miles a day and climb stairs, but they cannot run.
  
  
• Prosthetic hips should not be flexed beyond 90 degrees, so patients must learn new ways to perform activities requiring bending down, for example, tying a shoe.

Limitations after knee surgery include the following:

• Walking distance improves in 80% of patients after knee replacement surgery but patients still cannot run.
  
  
• Only slightly more than half of patients report improvement in stair climbing. (Artificial knee joints generally have a range of motion of just 110 degrees.)

Failure Rates. Joint replacement represents a great medical advance, but it is not failure proof. Failure rates depend on certain factors, including materials used.

• Cement prostheses have a particularly high rate of bone loss and loosening, apparently largely due to cement deterioration. In general, studies are reporting reoperation rates of over 30% after 10 years. Fortunately, advances in cement and prosthetic implants are improving the implant survival rates and reducing the need for revision procedures.
  
  
• Uncemented arthroplasty using porous material is showing very good results. Studies now report that after 10 years, 5% of patients require reoperation and 12% of patients report some thigh pain. According to one 10-year study, even among patients who had experienced reduction in hip bone density after the procedure, 86% reported either no or mild hip pain and 95% still had less pain than before the procedure. No revision surgeries had been performed.

Revision Arthroplasty

A repair procedure called arthroplasty revision may be used in cases where the original transplant fails. The specific procedure depends on whether the bone defects that occurred are contained or uncontained.

• Contained defects can be repaired with small bone grafts, the use of cement, or oversized cementless implants as required.
  
  
• Uncontained defects are more severe and may require a large bone graft or specially constructed implants to restore bone.

If a second arthroplasty is required, the potential for complications is magnified: more bone is cut, more blood is lost, and the operation takes longer. The patients are also generally older and more vulnerable to complications.

Other Joint Procedures