They are the chorus line of the evening news, the pinups of Modern Maturity: senior citizens in perpetual motion, heedless of arthritic knees, hips and shoulders, dancing, jogging and bicycling their way through a world populated exclusively by gleeful grandparents and adoring toddlers. They are, of course, fictitious. Bee Jay Janiga, 73, is a real person with arthritis and, like the ones in the commercials, she takes one of the new class of drugs known as Cox-2 inhibitors. She dances, too--in fact, she's been a professional since she began performing at the age of 14, and she still leads a touring dance troupe, the Racquettes (minimum age: 50).
What she doesn't do is climb stairs, walk her dog or attempt to sit still for the length of a concert. "You put a smile on your face and you perform," she says of the uneasy relationship between her art and her aching knees. She isn't complaining--but she isn't exactly celebrating, either.
The twingeless grandparents of the TV ads are the shock troops in one of the bitterest marketing battles of the year, pitting the makers of Celebrex and Vioxx--two breakthrough anti-arthritis drugs--against both older medications and each other. Last week the battle took on a new intensity when a leading cardiologist reported that the two drugs could pose a small but disturbing additional risk of heart attack--a connection that the drugs' manufacturers said was taken out of context. "There are a lot of holes in this drug class that haven't been tackled yet," says the author of the study, Dr. Eric Topol of the Cleveland Clinic. "But from watching TV you'd think you'd be dancing in the street." The subject is of intense interest to the roughly 21 million Americans with osteoarthritis, suffering joint pain that ranges from the annoying to the crippling. Dr. John Klippel, medical director of the Arthritis Foundation, expects that figure to rise to about 30 million by 2020, when the entire baby-boom generation will have passed 55. For them, the question is whether their future will be like the fictitious "Ann" in the Celebrex commercial who doesn't let arthritis interfere with her tai chi classes--or more like Janiga, who dreads the day when she will be driven to the extreme step of surgical replacement of her knee joints, buying probable relief from pain at the certain price of ending her dancing career forever.
She faces such a stark choice because osteoarthritis, a disorder seemingly as straightforward as a rusty hinge, is in fact a dauntingly complex and intractable problem. Medicine offers either palliative pain relief or radical surgery, but almost nothing in between that can reliably alter the course of the disease--although exercise, weight loss and dietary supplements such as glucosamine and chondroitin all have shown promise in treating the symptoms, and hucksters have been happy to fill the therapeutic void with strap-on magnets and copper bracelets (sidebar). The field is still searching for a biomarker--a chemical substance whose presence can serve as a reliable measure of the progress of the disease, or of treatment. That is a particular problem because the pain of arthritis is so subjective and variable, changing from day to day for no apparent reason. Last month the National Institutes of Health joined with four pharmaceutical companies to look for such biomarkers. "This was sort of a scientifically sleepy disease until maybe about seven or eight years ago," says Dr. David Felson of Boston University. "We finally woke up and said we have to put more resources into it because it's such a prevalent, disabling problem."
But for drug companies, arthritis has been a boon: a nonfatal, incurable disease that may require patients to take pain-relief medication every day for decades. This explains the phenomenal success of Celebrex and Vioxx. Since their introduction in 1999 the two drugs have captured more than 60 percent of the $6.6 billion arthritis-drug market--a figure that doesn't even include products like acetaminophen, which are used to treat other conditions as well. They were promoted remorselessly on television--a little too remorselessly for the Food and Drug Administration, which ordered the manufacturer of Celebrex (Searle, which is now part of Pharmacia) to tone down commercials that "overstate[s] the efficacy" of the drug. The company obligingly changed the tag line on its jingle--to "Come on and celebrate" from the somewhat more specific "Do what you want to do."
The advertising tended to obscure the fact that the two drugs basically have the same effect as any number of existing medications, including aspirin--that is, they relieve pain and reduce inflammation. "The reality is that these drugs have been tested against aspirin and found to be equivalent," says Dr. Harvinder Luthra, head of rheumatology at the Mayo Clinic. Dr. Roland Moskowitz, president-elect of the Osteoarthritis Research Society International, believes that the first line of treatment for mild to moderate arthritis pain is exercise and over-the-counter analgesics such as acetaminophen, followed by the class of drugs known as NSAIDs (for "nonsteroidal anti-inflammatory drugs"): ibuprofen, naproxen, piroxicam and diclofenac. These work by blocking the production of prostaglandins, hormonelike substances that trigger inflammation. But prostaglandins also control the secretion of gastric juices and the mucus that lines the stomach--which is why prolonged use of NSAIDs can lead to ulcers and potentially life-threatening gastric bleeding. The advantage of the Cox-2 inhibitors is that they target the specific prostaglandins that cause inflammation without suppressing those that protect the stomach. The main disadvantage, at least until now, has been that they are relatively expensive--from $3 to $6 a day--and many insurance companies have been reluctant to pay for them unless patients can demonstrate that they were at high risk for gastrointestinal bleeding; just being old isn't necessarily enough.
Last week, however, the field was rocked by a paper in The Journal of the American Medical Association speculating on another downside to the two drugs--a small increase in the risk of "cardiovascular events," including heart attacks and ischemic (clot-related) strokes. Topol, the author, suspects this is because the drugs promote the formation of blood clots. But he did not study the two drugs directly; instead, he analyzed data from existing studies, including some by the manufacturers themselves. "We're not talking about a panic attack," he said, "but a small, quantifiable risk that needs to be studied."
Spokesmen for Pharmacia and for Merck (the manufacturer of Vioxx) were quick to dispute Topol's conclusions, pointing to additional studies that he failed to consider and which, they claim, showed no added risk from their products. Dr. Steve Geis of Pharmacia says the company has "no evidence that [Celebrex] causes blood clots." The issue is complicated because some of the studies compared the Cox-2 drugs with the older class of NSAIDs. At least one of those compounds, naproxen, is an anticoagulant (like aspirin) which can reduce the risk of heart attacks--making for an unfair comparison, according to Merck. Topol admitted that his tentative conclusions needed to be tested in clinical trials--but meanwhile, he strongly recommends that patients at risk for heart disease take an anticoagulant, such as low-dosage aspirin, along with a Cox-2 inhibitor. "Nobody with coronary disease ought to be taking these medicines alone," he told NEWSWEEK. On the other hand, he said, "I'm not worried about patients without heart disease"--including himself. Topol has osteoarthritis in both knees--which he treats with occasional doses of either Vioxx or Celebrex, depending on his need; he finds Vioxx's effects seem to last longer.
At 47, Topol is on the leading edge of what rheumatologists suspect is a looming epidemic of joint pain. The most obvious fact about osteoarthritis is that its incidence rises with age. But the increase appears to set in much earlier than previously believed. Historically, researchers studied osteoarthritis only in people over 55, but MaryFran Sowers of the University of Michigan has been studying a cohort of women between 25 and 55 and found that the average age of onset for the disease is between 40 and 45. "It goes from not being discerned in the 35-to-40 range to a jump of 8 percent in the 40-to-45 range, and then it jumps again," she said; on average, each year after the age of 40 sees a 2 percent increase in the rate of osteoarthritis.
That epidemiology suggests a regular process, as if joints were simply wearing out over time. What surgeons see inside arthritic joints does, indeed, look like wear and tear, particularly on the cartilage--the rubbery, slippery cushion on the ends of the bones that ordinarily provides a smooth surface for motion. Damage to the cartilage is often--but not always--accompanied by pain, although researchers aren't even sure exactly why. In the later stages of the disease, bone rubs and grates excruciatingly on bone. Often the bone sprouts knobby outgrowths, called spurs. Patients sometimes compare the pain to a toothache, insistent and deep. "The pain will eat you up eventually. It's there all the time, walking, sitting, even sleeping," says Brian Hoose, 61, whose arthritic hips, which he first noticed five years ago, caused him to give up successively tennis, walking his Russell terriers and eventually, driving. "If you had seen me walking, you would have thought, 'That guy's 90 years old'."
Inflammation and swelling often accompany the pain. Tony Evans, a 51-year-old preacher and the team chaplain for the Dallas Mavericks, says his arthritic left knee balloons to a size "between an orange and a grapefruit" when he plays basketball these days. When the swelling is at its worst, Evans's doctor has to drain the fluid around the knee with a syringe. In the most serious cases, the joint becomes virtually immobilized. Deborah Moraza, who is only 46, sometimes can barely walk across a room; she carries a cane in her car and leaves a pair of crutches in her office. She cannot kneel and sometimes can barely sit; she watches television stretched out on floor pillows and when she needs to stand, rolls over onto her front, assumes a push-up position and walks her feet and hands together, bending at the hips--"like a spider," she says. "A spider's knees don't bend and neither do mine." Recently the pain has spread to her thumbs, meaning she's had to learn to write all over again: "If I hold my pen like normal people do, I pay the price."
Simple in concept, on a biomolecular level the deterioration of cartilage is just the end product of a complex and still-mysterious process. Cartilage does not, it appears, simply wear out from use over time, like a piece of fabric. This should be obvious from the fact that people use both knees at the same rate, but may get arthritis in only one. "It is not a normal part of aging," says Klippel. "The vast majority, even as they age, don't really have any problems." Although X-rays usually show the telltale narrowing of cartilage between their bones, most escape without serious symptoms. Why do some people get the disease and others escape without pain? A few may be genetically programmed for it, perhaps because of defects in their production of collagen, the protein that is the structural component of cartilage. Certain enzymes seem to play a part, and these may be affected by hormone levels; women are three times more likely to suffer from osteoarthritis than men. Obesity is a significant risk factor, which makes intuitive sense; a pound of added body weight places from two to four pounds' extra stress on the knees and hips during routine movement, estimates University of Chicago rheumatologist Dr. Michael Ellman. But the actual mechanism by which cartilage deteriorates under mechanical stress is still not understood. And, to state the obvious, being fat doesn't place any added demands on your fingers or elbows.
It turns out that one of the biggest risk factors is as obvious as falling down the stairs. Unsophisticated as it sounds, researchers are coming to appreciate the role of simple joint trauma in the early development of osteoarthritis. Injuries that seem to heal perfectly well appear to set up a process of deterioration that can have devastating effects decades later. In one study, a knee injury before the age of 22 resulted in a threefold increase in the incidence of arthritis in the same knee, typically striking by the mid-50s. "Cartilage does not have the ability to repair itself like other tissues," says Luthra. He draws an analogy to a car tire, which is supposed to last about 40,000 miles under normal conditions. "But if you drive over glass and the tire gets cut, it's going to wear out faster. Cartilage is made by nature to last a lifetime,"--but not if it's damaged. And it isn't only damage directly to the cartilage itself that causes problems, but also injuries to the ligaments, the elastic bands of tissue that connect the bones and keep them in alignment. Torn or stretched ligaments around the weight-bearing joints result in instability and unnatural stress on bone and cartilage, which may set off the process of deterioration.
Of course, the injury need not be sustained in one cataclysmic episode; long-term or repeated trauma can have the same effect. This obviously is the case with many athletes, even those who don't injure themselves in contact sports. Moraza, the woman whose knees don't bend, played softball, baseball, tennis, track, basketball, volleyball and field hockey as a student, and by her 30s had dislocated her shoulder so often that it would pop out in her sleep. And some people just have the bad luck to be born with poor biomechanics--hips that curve at an unnatural angle, for example. For them, just walking may set off the process that leads to osteoarthritis down the road.
Yet, the experts all rush to add, this is not an argument against walking. On the contrary, low-impact exercise is strongly recommended as a way to prevent arthritis. "Don't think exercise will cause it," says Dr. Kenneth Cooper, founder of the famed Cooper Aerobics Center in Dallas. "It will aggravate an existing condition. But in most cases, it's going to protect you." Exercise helps in two ways, by weight reduction and by strengthening the muscles, which, along with the ligaments, stabilize and support the joints. Sharon Coyle, a physical therapist who got her first twinge of arthritis in her right hip at 50, has taken this advice to heart; at 56, she had a total hip replacement and now, a year later, she is keeping pain at bay with thrice-weekly water exercises. "When you have arthritis, you have to move," she says.
If she can hold out, more relief may be on the way. Both Merck and Pharmacia have second-generation Cox-2 inhibitors in the pipeline, at least one of which, Pharmacia's valdecoxib, may be on the market by early next year. The companies have said very little about the new drugs, although industry analysts speculate that they may have what drug companies call a better "safety profile." (After the stellar launches of Vioxx and Celebrex, sales have shown signs of leveling off this year, analysts say.) And new techniques for repairing damaged joints are showing promise. In one, doctors inject joints with a synthetic derivative of hyaluronic acid--a gooey fluid that lubricates normal joints and is lacking in arthritic ones. The procedure, which has been approved only for knee joints so far, requires a series of injections costing about $1,200, but can provide relief for up to a year. Even more impressively, doctors can now culture cartilage cells in vitro (after harvesting them from the patient's own body) and inject them into a diseased knee joint, where they multiply and knit themselves into a new matrix of protective tissue. So far, only patches less than an inch across have been successfully implanted, so the technique is used more to repair cartilage damage before full-blown arthritis sets in.
The ultimate treatment for osteoarthritis is to replace the damaged joint with an artificial one. The procedure is rapidly growing in popularity as more patients reach the end of the road with medicine, and the metal-and-plastic joints become more reliable. Ten years is considered a minimum life span for a replacement joint and some last as long as 20. This year American surgeons will perform as many as 267,000 total knee replacements (more than double the figure from 1990) and 168,000 artificial hip implants, up by a third from a decade ago. Brian Hoose got two of them last spring, and six weeks later he reported that for the first time in years he was able to sit without pain. "I'm looking forward to a great 10 years ahead of me, where before I had no life to look forward to at all. You get new hips and away you go."
Yes, that's what we all want: lives free of pain, a chipper old age, like the happy grandmas playing patty-cake on the TV commercials. We exercise and we take our supplements and we down our pills and we hope for the best, like Janiga, the dancer, who accepts the fact that after six decades of dancing her knees may finally have betrayed her. "I think I'm a good example for all the people in my exercise classes," she says gamely. "You have the pain. You put a smile on your face and you try to be normal."ARTHRITIS AND RELATED CONDITIONS AFFECT ONE IN EVERY SIX PEOPLE--TOUGH ODDS, NO MATTER WHO YOU ARE
After two surgeries to soothe an aching right knee, he still can't play basketball or tennis. 'The good news is it doesn't affect my golf game one bit.'
At the height of her career, 'Balanchine's muse' was diagnosed with arthritis in her right hip. Eighteen years later she still teaches almost daily.
Hall of Fame Jockey
Knee pain almost put Stevens to pasture, but glucosamine and hot baths helped him win the Preakness.
Queen of England
Her hip was replaced, and the queen is reported to have arthritis in her fingers. Too much waving?
Diagnosed in'93, he treats the pain in his right knee and elbow with exercise. 'And Advil' (his sponsor).
She reportedly discovered arthritis in her right hip while recovering from replacement surgery on her left
Super Bowl Champion
Namath, 58, has fought arthritis pain since he was 23. His knees were replaced in 1992, but he still has it in his hands and spine.
As one of the major weight-bearing joints of the body, the knee is particularly vulnerable to arthritis pain. Mild symptoms can be managed with pain relievers, while more extreme cases may require surgical replacement of the knee.
In the normal knee, cartilage coats the ends of adjoining leg bones, providing a protective buffer against wear and tear. As the joint bends, bones glide across each other with one fifth the friction of ice against ice.
A fibrous matrix of protein, water and shock-absorbing molecules
Supportive tissue that connects the bones together
The larger of the two lower leg bones
In osteoarthritis, the cartilage loses its resiliency, and starts to break down under the constant strain of knee movement.
1) EROSIONS: Obesity, injuries, aging and repetitive use can all cause the cartilage to wear away
2) FRICTION: Exposed bone surfaces grind against each other, resulting in pain, swelling and difficulty moving the joint.
3) BONE SPURS: Continual strafing causes bones to sprout abnormal growths, or spurs.
When other treatments fail, total knee replacement surgery is an option that can alleviate the pain of arthritic joints.
1) SHAPING: The damaged bone is cut away and carved to make room for the implants
2) PROSTHETIC: New synthetic surfaces are cemented into place, protecting bone ends from rubbing
3) RECOVERY: The new joint should allow patients to return to normal activity and usually lasts up to ten years