Fast pace of new research
Research over the past fifty years has brought about major advances in finding causes as well as better ways to treat arthritis. The pace of improvements have quickened in recent years. New findings have helped reduce deaths" correct deformities restore movement and reduce pain.
More than 200 years ago a gout attack kept the English statesman William Pitt from stopping the passage of a tax on tea by Parliament. The tax led to the Boston Tea Party and the independence of the American colonies. In the past 40 years researchers have found ways to control the arthritis caused by gout so that no one today need miss an important day from work.
More than 50 years ago crutches or canes were the only way to get around once rheumatoid arthritis or osteoarthritis destroyed a hip or knee joint. In the past 30 years research has created artificial joints--spare parts for people with arthritis. Replacing worn-out joints with artificial ones has given back freedom of movement to thousands of people who thought they had lost it forever.
More than 10 years ago a mysterious new form of arthritis began disabling children and adults along the Connecticut shoreline. In seven years researchers identified the cause of Lyme disease as an infection spread by ticks and found an effective treatment with antibiotics.
Today progress is so fast in some areas of arthritis research that the media often report a new finding even before the medical journal with the study reaches your doctor's office. Often this rapid transfer of research information includes very early results that need further study before your doctor can apply them.
Before World War II little could be done to help people with arthritis. But during and immediately after the war a number of discoveries excited scientists and launched a new emphasis on arthritis research.
Studies of military recruits linked a strep throat infection to rheumatic fever. Penicillin proved an effective way to prevent rheumatic fever as well as to cure arthritis related to many types of infectious diseases. Rheumatoid factor and the LE cell two types of markers in the body for specific types of arthritis were first identified during this period. The forties ended with a Nobel Prize for the discovery that cortisone controlled inflammation.
During the same time two other things happened outside medical research to help promote arthritis research. In 1948 the Arthritis Foundation began to raise voluntary contributions from the public to fund arthritis research and train new researchers. In 1950 Congress formed the National Institute of Arthritis and Metabolic Diseases to provide government funding for arthritis research and research training.
In the ensuing years increased support helped researchers better identify and classify the more than 100 arthritis-related diseases. In turn this helped improve diagnosis and allowed development of specialized treatments for specific types of arthritis.
Since the 1960s the pace of arthritis research has once again quickened as it did in the 1940s. There have been major advances in our ability to recognize and control certain types of arthritis.
For instance better management of lupus complications increased the number of people who lived five years or more after diagnosis from 50 to 98 percent. Newer drugs proved effective at reducing pain and decreasing inflammation as well as in some cases actually slowing disease progress. The use of acrylic cement and the development of high density plastics helped solve some of the problems in the loosening and wear of artificial joint replacements.
|1978||Better management of scleroderma||Improved survival|
Today scientists are looking at four broad areas of research: causes treatments education and prevention. Much of the research discussed here involves early findings. Some of these results need to be repeated in other studies before they are accepted by most scientists.
The causes of most forms of arthritis are unknown. Therefore doctors try to treat symptoms rather than attacking the roots of the problem. This is why so much research focuses on how the healthy body works and what goes wrong in arthritis. By understanding what causes arthritis researchers hope to design better methods for diagnosing treating and even preventing some arthritis-related diseases.
Research into the causes of arthritis became fast-paced in the 1980s because of the development of new techniques in molecular biology. Molecular biology is the science that studies how molecules in our cells (the smallest parts of our body) work. Research in this area has greatly advanced our understanding of how our body's defense system works and what happens when it fails.
Research into causes of arthritis looks at how four factors work alone and together to produce disease. These four factors include how the body itself contributes to the disease process and the roles heredity infections and the environment play.
Researchers are trying to understand how the body itself contributes to the disease process. They are studying how the body works and what changes accompany various types of arthritis. For instance researchers are trying to understand how the parts of the joint work and what happens when they fail. One major part of a joint they are examining is cartilage.
Cartilage is a resilient material that covers the ends of bones and prevents them from rubbing together where they meet in a joint. It serves as nature's shock absorber by changing shape as the joint moves. When you put weight on your knee the cartilage flattens. When you relax the cartilage expands.
Researchers have discovered that early in osteoarthritis chemical changes result in the loss of two types of fibers proteoglycans and collagen which help give cartilage its resiliency. At the same time enzymes called proteases--which normally destroy old cartilage so it can be replaced by new growth--begin destroying cartilage much faster than it can be replaced. This process seems to happen faster in some people and studies are under way to find out why.
Another key question is how the immune system protects the body from the destruction of inflammatory types of arthritis. In the immune system there are specialized cells and a special family of proteins called antibodies as well as other chemical substances that help control and modify how the system responds. Among these chemical substances are interleukins and gamma interferon which are made by the immune cells. These substances appear to be involved with certain types of arthritis.
Inflammation which involves swelling redness and heat is one of the immune system's responses in several types of arthritis. Studies have found that high levels of a group of chemicals called prostaglandins result in inflammation. Researchers have found for instance that aspirin interferes with the production of prostaglandins.
Scientists are researching how heredity increases risk for certain types of arthritis. Heredity may help explain why some kinds of arthritis such as ankylosing spondylitis and rheumatoid arthritis strike people of various sexes and races differently. Some genes may carry a set of instructions that increases the chances for developing certain types of arthritis.
For instance people with HLA-B27 a genetic marker are more likely than the general population to develop ankylosing spondylitis and several other related types of arthritis. Several North American Indian tribes have higher levels of HLA-B27 and more ankylosing spondylitis. Some specific genes have already been identified for ankylosing spondylitis, gout, psoriatic arthritis, rheumatoid arthritis and systemic lupus erythematosus.
A third area of research into causes of arthritis looks at how infections set off or slow down the immune system's response. It seems that in some forms of arthritis infections combine with a faulty gene to set off one or more malfunctions in the immune system. This causes the immune system to make errors. Instead of protecting healthy parts of the joints and other sites in the body the system turns against itself. This condition is called autoimmunity.
Autoimmunity results from the actions of substances called T cells or autoantibodies. T cells are specialized white blood cells which help distinguish between the body's own tissues and foreign invaders. Antibodies are specialized white blood cells that protect the body by attacking and destroying foreign invaders. For reasons not yet clearly understood in autoimmunity antibodies recognize healthy parts of the body as foreign and attack them. Researchers call these antibodies that attack healthy parts of the body autoantibodles.
Scientists are now studying why certain people make T cells and autoantibodies which cannot distinguish healthy parts of the body from foreign invaders and whether they can cause disease symptoms. Autoantibodies may also serve as a kind of name tag to indicate people who are more likely to develop certain kinds of arthritis.
Scientists think that bacteria and viruses may help trigger malfunctions in the immune system. They have already linked bacteria to infectious arthritis and Lyme disease. Researchers are now looking at how certain viruses such as the Epstein-Barr virus of infectious mononucleosis or the HIV virus of AIDS may trigger other types of arthritis.
Researchers are also trying to understand a process called molecular mimicry. In this process substances in the body look like or mimic an invading virus and thus set off destruction of healthy parts of the joint.
The fourth factor in research into the causes of arthritis environment is getting renewed attention. Here scientists are looking at how where and how you live influence your risk for certain types of arthritis.
For instance researchers have long been intrigued by variations in disease patterns among countries especially in rheumatoid arthritis. Scientists are now looking at remains of Indians in North America to see if rheumatoid arthritis was a new disease a mutation from another disease or a disease that spread during colonization from the New World to the Old.
Historical records and skeletal remains suggest that rheumatoid arthritis appeared in Europe as late as 300 years ago. New findings in North American Indian skeletons from 1200 years ago suggest that rheumatoid arthritis is a New World disease that spread to the Old World. Scientists are now looking for what caused the disease to spread. The answer may help us understand what causes rheumatoid arthritis.
Several studies indicate that certain injuries can lead to arthritis. Football players who have suffered twisting injuries to the knees have an increased likelihood of getting osteoarthritis of the knees. Early findings suggest that certain repeated movements done over a long period of time by some workers may injure a joint. More research is needed in both these areas before we can understand how they may be involved in arthritis.
Researchers are looking at how the body's defenses heredity infections and environment or lifestyle interact to cause certain types of arthritis.
Many tests have been developed to aid doctors in diagnosing various types of arthritis. In addition research has helped doctors look for patterns of symptoms associated with certain types of arthritis. For instance in fibrositis doctors look for chronic muscle aches in more than three sites sleep disturbances acutely painful tender points in certain parts of the body and the lack of any underlying illness. Researchers are now looking at new findings on decreased blood flow decreased endurance and cold sensitivity.
New drugs have been developed to slow down the immune system's response in rheumatoid arthritis and lupus. Some of these drugs are borrowed from treatments for cancer and transplant surgery. In arthritis these drugs are used at lower doses but still have many unwanted side effects. Researchers are currently testing whether changing the way drugs are given or combining two drugs at lower doses works and has less side effects. Early results from some combinations of specific drugs suggests this combination therapy may help reduce side effects.
Recent research on nonsteroidal antiinflammatory drugs has concentrated on reducing their side effects to the stomach. These drugs such as ibuprofen are widely used to stop pain and inflammation in arthritis. However some people cannot take them because they cause stomach problems. Scientists have been looking at anti-ulcer drugs and other ways to reduce the impact of chronic use of nonsteroidal anti-inflammatory drugs on the stomach.
How diet affects the response of the immune system in arthritis is a central question in a number of diet-related research studies. For instance dietary factors can affect the immune system's inflammatory response. In some studies there has been a modest lessening of subjective symptoms. Several researchers have observed that fasting low calorie/low protein diets and the fatty acids in fish oils slightly reduce some symptoms of rheumatoid arthritis. Scientists do not yet understand why this happens or if certain changes in diet such as short-term fasts help.
Artificial joints have helped many people with arthritis in their hips knees or even fingers regain lost movement. They have been especially helpful in reducing pain and correcting deformity in people with osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.
Research into treatments is also looking at:
- magnetic resonance imaging in diagnosis
- improving access to care
- sleep disturbances
- functional status
- pain control methods
Researchers are also looking at what people with arthritis can do to help themselves. They have shown that some aerobic exercises which are good for the heart are also safe for the joints. People with arthritis who did these exercises regularly reported less pain and fatigue.
Researchers are also studying ways to increase people's feelings of control which is called self-efficacy. Studies in education show that it is not how much people learn but how much they feel in control that helps them cope with arthritis.
Stopping arthritis before it ever starts or preventing disability once you have arthritis holds the greatest hope for the future. Research is just beginning to pick up steam in the area of prevention.
Doctors have long suspected that being overweight puts stress on the knees. Three recent studies have now confirmed that obesity increases the risk for developing osteoarthritis of the knees.
Recent studies have looked at what helps keep workers with arthritis on the job rather than on disability. These studies suggest factors related to the job rather than to disease severity cause a worker to stop working. Factors such as the physical demands of the job and the lack of control over pace or work seem to increase your chances for disability if you have arthritis. Age and the presence of other health conditions are also important. Studies now need to be done to see if changing job-related factors helps keep workers with arthritis employed. Research in prevention is beginning to identify factors such as obesity and work patterns that increase risk for disease or disability.
Research in prevention is also looking at diet injuries and social support.
The future of arthritis research
Research in arthritis holds great promise for discoveries that will help many people.
Scientists may be able to correct malfunctions in the immune system. They may be able to immunize people against bacteria or viruses that trigger some forms of arthritis. And they may be able to prevent types of arthritis from ever happening by identifying and eliminating those factors that cause them. One of the biggest areas of future research will concern genes and gene replacement. Some forms of arthritis probably result from genes that have the wrong set of instructions. For example several types of gout result from such genes. If scientists can find out exactly how genes influence the development of a particular type of arthritis they may eventually be able to replace a gene that increases your risk for disease with one that carries no increased risk. Sometimes scientists find things that cause or increase our risk for disease by studying differences in patterns of disease in large groups of people. This area of study is called epidemiology. For example almost everyone over 65 shows signs of osteoarthritis on X-ray. But only one-third of those with X-ray evidence of disease ever feel symptoms. Why? Studies of differences in disease patterns may offer us some clues to the answers. Women get some arthritis-related diseases--such as rheumatoid arthritis, lupus and osteoporosis--more often than men. Scientists are now studying the effects of both male and female hormones in some types of arthritis.
For instance women develop osteoporosis after menopause when a drop occurs in levels of the female hormone estrogen. Symptoms of rheumatoid arthritis and lupus may temporarily disappear while a woman is pregnant when female hormone levels are high only to come back after the baby is born. Yet an eight year study of nurses failed to show a reduced risk for rheumatoid arthritis in women who used birth control pills containing estrogen. Researchers are trying to discover how hormones work to protect or expose people to some arthritis related diseases.
Today progress is so fast in some areas of arthritis research that the media often report a new finding even before the medical journal with the study reaches your doctor's office. Often this rapid transfer of research information includes very early results that need further study before your doctor can apply them. As a consumer you now need to know how to critically evaluate research reported in the media.
Suppose you read in a newspaper about a study reported in a medical journal that an industrial chemical helped improve skin pliability in 19 people with scleroderma an arthritis-related disease that causes hardening and thickening of the skin. Sound promising?
The treatment described in this article was an early study on dimethyl sulfoxide (DMSO). DMSO is an industrial solvent often used as a degreaser. Early studies without control groups showed some promise. But the Food and Drug Administration refused to approve DMSO until enough evidence on the safety and effectiveness of the drug had been gathered. Yet media reports and enthusiastic supporters led 10 state legislatures to legalize DMSO.
Eventually a large randomized controlled study in 13 clinics across the country failed to confirm that DMSO was effective in treating skin problems in scleroderma. Over one-quarter of the people treated with DMSO in the study had to discontinue the treatment because of skin blistering and peeling.
Because research results get reported in the media even before they are published in medical journals consumers need to know how to critically evaluate claims. How can you tell if reports such as the example on DMSO are really promising?
Ask yourself these questions:
- Is there a scientific reason to think the results are likely?
- Are the results reported for large groups of people a small number of people animals or laboratory studies?
- Were the people in the study like you? (Same age same sex same race same type of arthritis?)
- Was there a control group--a group that did not receive the new treatment?
- Have the results been repeated by other researchers with similar findings?
- Has the research been published in a medical journal?
- Does the report use any qualifying words to describe the findings (such as some may preliminary or experimental)?
- Does the report list any questions that still must be answered before the results can be applied?
- Does the report suggest health actions that people with a specific type of arthritis should take as a result of the research?
When you read or hear about a research study in the media it is important to know if what is being reported is (1) an early finding (2) an unproven remedy or (3) a confirmed result that you can use to take health actions. You can use this list to look for some of the same clues in news reports that researchers use when they review a study in a medical journal.
Evaluating new research
Researchers start with a hypothesis a prediction based on research findings up to that date about why something happens or fails to happen in the body or the outside environment. They look for a biological reason or explanation based on what we already know about how the body works.
For instance some people apply industrial lubricating oil to the joints in the mistaken notion that if oil makes a machine move smoothly it will also make a joint move easily. This notion does not make biological sense because a special fluid in the joint called synovial fluid lubricates the joint not oil. When you are reading a report about a new treatment look to see why or how scientists think the treatment works.
Reports of results in a small number of people can seem promising only to prove faulty when tried in large numbers. For instance in the 1980s several arthritis drugs had to be pulled off pharmacy shelves because rare but serious side effects showed up only after they were used by millions of people. When you hear about new research results find out if the study was done in test tubes animals or a small or large number of people.
Look at the similarity of the groups
Researchers test new treatments on groups of people who are similar in age sex race and specific type of arthritis. The reason is that if one of these factors is not the same in all groups it could cause different results.
For instance a treatment that works well in adults may not be safe for children with certain types of arthritis because they are still growing. If you are reading about research findings see if the group in the study was similar in age sex and type of arthritis to you or someone you know with arthritis.
Check whether a control group was used
Studies usually compare a new treatment with one whose effects are already known. The group that receives the new treatment is called the experimental group. The group that receives the known treatment (or sometimes no treatment) is called the control group. Neither the investigators nor the people participating in the study know who is getting the new treatment until after the study is completed. This is called a double-blind study.
Control groups and blind studies help show the results are due to the new treatment and not to some other factor. Since symptoms of arthritis can come and go it is important to know that it was a treatment and not the disease itself that caused a change. Look for control groups in the research reports you read.
Was the study repeated?
A single study rarely gives a final result. Scientists repeat studies to be sure that the results are not due to chance or some factor other than the new treatment. That is why articles in medical journals include a review of other studies on the topic and a comparison of results.
For instance 32 researchers in the United States and England working on four different studies tested low doses of the anti-cancer drug methotrexate in people with advanced rheumatoid arthritis. All the studies showed similar benefits as well as the risk of side effects. When you're reading a report about a study look for references to similar findings by other researchers.
Was the study published?
Sometimes promoters of unproven remedies will use the media books direct mail or other methods to bring public attention to their theories or product. Some of these reports can look like research studies.
Researchers submit their findings to medical journals that are read by experts in arthritis research and care. Before publication experts review the methods used in the study and recommend whether the study should be published. If you read or hear about a research report look for a reference to the journal that published it.
Are there qualifying statements?
Research studies usually end with a discussion or interpretation of the results and qualifications of their use. For instance authors may note that this is an early finding and call for similar studies by other scientists. Look in media reports for these qualifying statements.
Are there unanswered questions?
Research studies often end with a list of questions that still need to be answered before the results can be applied to health actions. Look for mention of these questions in media reports. For instance in a recent study of fish oils the authors noted that the study did not answer what was the best dosage to use in order to demonstrate reduced inflammation.
Most arthritis research studies focus on understanding one of the more than 100 specific types of arthritis. Discovering the differences and similarities in various types of arthritis helps researchers in their search for causes better treatments education and prevention. This section describes two or three selected results from current research for thirteen different kinds of arthritis.
Fibrositis or fibromyalgia
Fibrositis or fibromyalgia refers to a condition that involves pain stiffness and fatigue in muscles ligaments and tendons. Researchers are trying to improve methods to diagnose and treat the disease.
Sleep disorders chemical reactions in the brain or nervous system immune responses muscle disease personality and stress have been linked as possible factors in causing or triggering fibrositis.
Fibrositis-like symptoms can appear in some other types of arthritis. For example people with rheumatoid arthritis may also experience sleep disturbances and tender points. It is not clear how these symptoms are related.
Gout occurs when excess uric acid crystals collect in the joints especially the big toe and cause severe pain. Researchers are trying to eliminate some of the causes of gout.
Low levels of the enzyme HPRT result in too much uric acid build-up. Scientists have located the gene that passes on an inherited lack of this enzyme.
For over 100 years scientists have known that lead poisoning causes gout. Now they are trying to find out if exposure to small amounts of lead from jobs or hobbies such as stained glass can also cause gout.
Plans are under way for a federal health study to see how many people who have been told they have gout and are taking anti-gout drugs actually have the disease or just have elevated levels of uric acid in their blood.
Juvenile rheumatoid arthritis
Juvenile rheumatoid arthritis may cause children's joints to become inflamed deformed and sometimes damaged. Scientists are trying to understand what goes wrong with the body's immune system how the disease affects growth and what treatments used for adults are safe and effective for growing children.
HLA-type antigens have been associated with certain types of juvenile arthritis. Findings may help explain if some children are more likely to develop the disease.
Oral gold (auranofin) a drug used for adults with rheumatoid arthritis can be safely used in children and teenagers with juvenile rheumatoid arthritis.
Lyme disease results from infection by spiral-shaped bacteria carried by a tick that can affect joints and many different parts of the body. Researchers are tracking the spread of Lyme disease and studying it as a possible model for explaining what happens in rheumatoid arthritis.
Lyme disease has been reported in over 33 states since it was first described in 1977. Blood samples from over half the farmers tested in one midwestern state showed signs of infection from the spirochete or spiral-shaped bacteria transmitted by bites from infected ticks. Scientists are now wondering why just some people who are bitten go on to develop Lyme disease or the chronic arthritis that accompanies it. One study showed that people with HLA-DR3 or DR4 genes were more likely to develop chronic arthritis.
Similarities between changes in joints affected by Lyme disease and rheumatoid arthritis have encouraged researchers to look at what happens in Lyme disease as a possible clue to what happens in rheumatoid arthritis.
Osteoarthritis involves a gradual breakdown in joint tissue usually in the hands knees and hips. Researchers are looking for factors that cause changes in cartilage and bone and why such changes occur more rapidly in some people.
One byproduct of the rapid breakdown of cartilage is a substance called keratan sulfate. Researchers are working on a blood test for this substance that may help detect osteoarthritis in earlier stages.
Two studies have shown that people who are very overweight especially women have a greater chance of developing osteoarthritis of the knees. Very heavy black women appear to have an even higher risk. Early studies also suggest that twisting injuries to the knee and repeated knee bending may also increase risk.
Osteoporosis is a condition that causes bones in the wrist spine and hips to lose strength and break or fracture. Researchers are looking at risk factors that may help prevent the disorder and ways to provide better diagnosis and treatment.
Bone cells have recently been found to contain receptors for estrogen. Estrogen used for the first six years after menopause has been shown to protect against fracture.
Calcium and exercise are important for building stronger bones but their exact role in osteoporosis is hotly debated.
Psoriatic arthritis develops from the skin condition psoriasis and can cause swelling in fingers fingernails toes and sometimes the spine. Researchers are looking for causes and better treatments for this type of arthritis.
One gene has been linked to psoriatic arthritis and scientists are looking for others. Researchers are now studying whether people with psoriasis but not arthritis also have this gene.
Drugs that affect the immune system have been shown to be effective in psoriasis leading researchers to look closer at the role of the immune system in psoriatic arthritis.
Rheumatoid arthritis affects many joints especially the hands and feet as well as other parts of the body. Researchers are looking at the interaction of genes and infection in causing the disease as well as seeking better treatments.
Most people with rheumatoid arthritis carry a gene called HLA-DR4 or a similar one HLA-DR1. Scientists suspect other genes are related to rheumatoid arthritis. For instance one study showed a large number of people with rheumatoid arthritis in a family group had HLA-DR4 and a second gene.
About 80 percent of those with rheumatoid arthritis have an autoantibody called rheumatoid factor. People with certain chronic infections such as tuberculosis also have this factor in their blood. This suggests that an infection is involved in rheumatoid arthritis.
Two experimental drugs one of which controls the immune system are being tested in rheumatoid arthritis. Gamma interferon which the body produces has shown promise in small numbers of people. Therafactin a drug made from a complex sugar molecule has shown in early studies that it reduces inflammation.
Scleroderma and mixed connective tissue disease are related conditions that affect the connective tissues such as the skin and blood vessels. Researchers are looking for better ways to diagnose and treat these diseases.
Autoantibodies discovered in the blood have helped doctors separate the diagnoses of three very similar conditions scleroderma mixed connective tissue disease and polymyositis. A new technique using ultrasound is also helping measure skin thickness in scleroderma.
A drug used to treat severe high blood pressure called captopril has also been used to dramatically reduce blood pressure and protect the kidneys in people with scleroderma who developed a serious form of kidney disease.
Systemic lupus erythematosus most often affects young women and involves a disorder in the body's immune system that can affect many parts of the body including joints. Scientists are finding different genetic patterns and autoantibodies for lupus and its complications.
High levels of interferon have been found in people with lupus. Scientists are looking at interferon to see whether this substance which the body produces naturally contributes to lupus.
People with lupus make many autoantibodies against normal parts of the body. One autoantibody anti-native DNA occurs in about 80 percent of those with untreated lupus.