Arthritis: A Joint Effort
Government and Private Researchers Seek to Understand -- And Improve -- Treatment For Osteoarthritis
By Elia Ben-Ari
Special to The Washington Post
Tuesday, January 29, 2002; Page HE01
Jim Jensen, age 48, director of congressional and government affairs at the National Research Council in the District, officially joined the tens of millions of Americans with osteoarthritis this month, when his podiatrist diagnosed the disease in both his feet. It wasn't entirely a surprise.
Although he's relatively young for such a diagnosis, he suspected arthritis because his feet "would get incredibly sore sometimes -- not just walking, but in the morning, upon waking up." In addition to the pain, he noticed that his feet were very stiff at times. "I could hardly walk outside to get the paper," he says.
Now that Jensen knows what's causing the discomfort, the question is what can he do to maintain his mobility and slow the course of this disease, the most common form of arthritis.
"I'm only 48 years old. What's it going to be like 30 years from now?" Jensen wonders.
Unfortunately, there are no good answers. The best available therapies for osteoarthritis (See "Treating Osteoarthritis: Current Options" on Page F7.) relieve pain and improve function, but can't stop progression of the disease, a leading cause of disability that accounts for billions of dollars in health care costs and lost wages each year. If impairment becomes severe, joint replacement or other surgery is usually the only remaining option; osteoarthritis is the most common reason for total knee and hip replacement.
In the last decade or so, research has begun to shed light on what goes wrong in people who have osteoarthritis. Although these advances should provide opportunities to prevent, slow or even reverse disease progression, drug development and testing have been hampered by a lack of reliable, objective ways to diagnose the disease in its earliest stages or measure its progression.
Now, a collaboration between the federal government and private drug makers aims to address these problems, just as millions of Jensen's fellow baby boomers begin to swell the ranks of the afflicted. The National Institutes of Health (NIH) and four pharmaceutical companies (GlaxoSmithKline, Merck, Novartis and Pfizer) are joining to support a seven-year study of 5,000 people with early osteoarthritis of the knee -- one of the most commonly affected joints -- or at high risk of developing it.
The Osteoarthritis Initiative, set to begin recruiting patients in May 2003, will be the first study to characterize the onset and early progression of the disease, says Gayle Lester, program director for the initiative at NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Its findings could spur development of treatments that "can have a much greater impact on the population with regard to disease prevention," says Marc Hochberg, who heads the Division of Rheumatology at the University of Maryland School of Medicine and was part of a group that helped plan the initiative.
Results of this research are not expected soon, but the effort may offer hope for Jensen and others like him.
A Growing Problem
Researchers used to think osteoarthritis was a simple case of age-related wear and tear. But recent studies indicate the disease process is more complicated, varies among individuals and involves numerous risk factors. Furthermore, it remains unclear why some of the 21 million Americans with the condition have more pain and disability than others.
Although disease incidence increases with age, "growing older is not enough to explain osteoarthritis," says Washington rheumatologist David Borenstein. "There are people who get the disease much earlier on." In fact, about 6 percent of U.S. adults age 30 and over have osteoarthritis of the knee and 3 percent have hip osteoarthritis. While about 70 percent of those over age 70 have X-ray evidence of the disease in at least one joint, only half of them ever develop symptoms.
People with osteoarthritis have a progressive loss of cartilage -- the shock-absorbing tissue in joints -- and changes in the underlying bone, including formation of bony outgrowths or "spurs." Cartilage loss shows up on X-rays, but the degree of loss has not been found to be a reliable indicator of disease severity or progression. These and other changes in and around the joint lead to chronic and sometimes crippling pain, enlarged joints and limitation of motion. In some people, only one or two joints are affected, while in others multiple joints are involved.
Besides age and genetics (studies show that predisposition to the disease is sometimes inherited), risk factors include being female or overweight, having a prior joint injury or knee malalignment (being bowlegged or knock-kneed) and participating in high-intensity, high-impact sports. Also increasing risk are jobs involving repetitious tasks or kneeling, squatting and heavy lifting and -- for knee osteoarthritis -- weakness of the quadriceps muscle.
Some findings about osteoarthritis have surprised researchers.
For example, while being overweight is thought to be a risk factor for osteoarthritis because extra weight taxes joints, a few studies have associated obesity with osteoarthritis of the hands, which are not weight-bearing, suggesting that metabolic factors may also be involved. Research has revealed that cartilage is not just "an innocent bystander" in osteoarthritis, says Hochberg. "Cartilage is a dynamic tissue, constantly undergoing degradation and repair." In osteoarthritis, the normal balance between these two processes is somehow disrupted.
Often, researchers believe, disease is caused by the interplay of two or more factors.
For Steven Newman, 45, of Potomac, increasingly painful knee osteoarthritis resulted, he's been told, from his congenital bowleggedness along with the stress he put on his joints during 13 years as a marathon runner.
Newman says he wishes he'd known the risks of his "no pain, no gain" attitude 17 years ago, when doctors first diagnosed knee osteoarthritis after surgery for torn cartilage. Instead, he says, "I kept on with my activities, ran another marathon and continued to destroy my knees."
When a second arthroscopic surgery on his knees revealed serious degeneration, he gave up running at age 37. Two years later, a car accident left him with osteoarthritis in his right shoulder, forcing him to give up his dental practice.
Now, as associate director of education for the Washington chapter of the Arthritis Foundation, Newman sticks to low-impact exercise like walking and biking and manages his pain mainly through mental and spiritual approaches, because years of liberally gulping ibuprofen for the pain have left his stomach sensitive to medications.
The Game Plan
Researchers at the four to six clinical centers taking part in the Osteoarthritis Initiative will follow study participants for four to five years while providing them with "the highest standards of care," says planning group member Thasia Woodworth, who helps direct arthritis research at Pfizer Global Research and Development in New London, Conn.
The government and the drug firms will split the $8 million-to-$10 million yearly cost of the study.
Medical information collected during the study, including assessments of patient pain and function, and X-rays and magnetic resonance imaging (MRI) of joints, will be freely available to researchers worldwide. Blood and urine samples and DNA will be available to those who receive permission from an independent review committee.
Scientists will use these resources to identify so-called biological markers of disease and disease progression. These markers may include features of joint structure, such as bone spurs or cartilage thickness or volume, that show up on an X-ray or MRI, and substances in the blood or urine. They will also look for genetic factors that affect a person's risk of disease development or progression. A 1996 study indicated that genetic factors account for at least half of all cases of osteoarthritis in the hands and hips, and a smaller percentage in the knees.
At present, the most widely used method for monitoring disease progression in the knee is an X-ray measurement of the distance between bones in the joint -- which is thought to reflect the amount of cartilage present. (Unlike MRIs, X-rays do not show cartilage.) But some experts say this "joint-space width" is not a sensitive or reliable indicator of progression because some people have narrow joint space and little or no pain or loss of function, while others have pain and impaired function but no apparent joint-space deficit. Joint-space width also varies depending on exactly how the X-ray is taken.
The lack of sensitive disease markers means that clinical trials to test the safety and effectiveness of new drugs for osteoarthritis take at least two to three years and require large numbers of patients. This makes the testing very costly. Organizers of the initiative hope that identifying better markers will streamline clinical trials and spur development of drugs that modify the course of disease.
"Without reliable biomarkers, we will have a very hard time making decisions about taking drugs forward into the long development process that's likely," says Woodworth.
Meanwhile, some companies, including Pfizer, are moving ahead with development and testing of drugs that would have a huge and ready market.
"We can't stop trying to develop drugs for osteoarthritis, waiting for the results" of the initiative, says Woodworth. The hope, she says, is that the results will support methods of measuring disease progression that companies are already using to test next-generation drugs.
Moving Forward
Jim Jensen and his fellow boomers can't afford to sit idly waiting for a possible breakthrough either. As the search for better disease treatment continues, Jensen realizes some of the responsibility for maintaining his mobility and lessening the impact of the disease falls to him. Studies show that losing excess weight, exercising, learning about the disease and its treatment and taking an active role in its management all help reduce pain and maintain function.
Jensen is starting to explore what he can do. "I'm still terribly uneducated about the whole thing," he says. "So I intend to learn more."
He could probably learn a thing or two from Ruth Young of Sykesville, Md. After living with osteoarthritis for almost 50 years, she says, "I'm an expert in the subject."
Young first noticed the effects of osteoarthritis in her neck at around age 30, when she discovered she had trouble turning her head to look back when riding a bicycle. "Life changed when I couldn't ride my bike anymore," she says.
Now 79, the retired professor has arthritis pain in her neck, hands, feet, knees, hip and back. Still, she says, "I have not let it affect me too much, because I'm determined to overcome it." Although she has had to give up knitting and has trouble grasping a pen or holding a fistful of change, she still travels widely, swims every day and works with a physical therapist.
"You have to keep on moving," she says. "I've seen people who don't, and they freeze up pretty quickly."
Although exercise and a positive outlook, along with medications and hip replacement surgery, have provided some relief from symptoms, Young is impatient with how little is still known about osteoarthritis and its treatment.
"Arthritis has been known for centuries," she says. "I find it very irritating that they haven't made more progress. I don't care who has to partner with whom. Let's get on with it."
Elia Ben-Ari is a Washington area freelance writer. |
