More clues about what could be going on come from Olsen's research into the genetics of cartilage. For the past 10 years, he and his colleagues have been studying a group of families that develop advanced cases of osteoarthritis unusually early, in their 40s and 50s. So far, Olsen's group has identified at least three genetic variations that make the cartilage of these patients more susceptible to overloading. Other scientists have found at least a dozen cartilage-disrupting enzymes that appear to be overactive in osteoarthritis. Yet even the interaction between bones and cartilage doesn't tell the whole story. You also need to take into account the ligaments, those tough bands of tissue that connect bones to bones, and the muscles that surround and stabilize the joints. Ligaments can get stretched or torn, and muscles can atrophy from underuse, disrupting a joint's finely tuned mechanism.

Take, for example, the quadriceps, the large muscles on the front of the thighs that help raise and lower the legs. "It's common knowledge that patients with osteoarthritis of the knee will have weakness in the quadriceps," says Dr. Kenneth Brandt, a rheumatologist at Indiana University in Indianapolis. For a long time, physicians assumed this was because their patients' pain prevented them from exercising. But five years ago, Brandt and his colleagues began studying a group of 400 elderly people living in central Indiana and discovered, much to their surprise, that weakness in the quadriceps in some cases preceded the advent of osteoarthritis.

It makes sense. The stronger the muscles, the greater the load they take off the joint, thus limiting damage to the cartilage. Brandt's group is trying to determine whether healthy seniors who strengthen their quads by doing exercises with elastic-bands can delay, or possibly prevent, the disabling consequences of osteoarthritis in their knees.

However the arthritic process gets started, the damage to the joint eventually begins to grow. That's when the body's immune system gets into the act. White blood cells rush into the joint and release destructive proteins that chew up the bits and pieces of damaged tissue. This so-called inflammatory process, which is often but not necessarily accompanied by swelling, works well when the body needs to fend off an acute attack—say, from invading viruses or bacteria. But when the problem is chronic, as in osteoarthritis, the white blood cells may overreact, repeatedly releasing so many of their "mopping up" proteins that even healthy tissue is laid waste. In rheumatoid arthritis (see story), the immune-system response is particularly aggressive.

None of these processes occur in isolation. "Everything is failing together," says Dr. David Felson, a rheumatologist at Boston University. "That includes bone damage, the responses to that, muscle weakness, inflammation of the lining of the joint and ligament disruption." It follows that to be successful, any treatment will have to deal with all these factors.

So what can you do? The first step for most patients is to try to get some immediate relief. About 15% don't seem to experience inflammation; for them, over-the-counter pain killers like acetaminophen (Tylenol) are often all that's necessary to control their symptoms. Things become more complicated when inflammation is involved. Old standbys like aspirin or ibuprofen are pretty good anti-inflammatories, but long-term use can trigger dangerous side effects like internal bleeding. Newer drugs, such as COX-2 inhibitors Vioxx and Celebrex, are safer but no substitute for some of the long-term changes you may need to make.

Indeed, some researchers believe there's too much emphasis on drug treatments for osteoarthritis. "It's clear that there are other things that can improve symptoms as much as pills," says Indiana University's Brandt. Losing as little as 10 lbs. can make a difference, for example, as can strengthening the muscles that surround a joint. Certain exercises, such as tracing circles in the air with the arms, have also proved helpful at keeping the joints from stiffening and losing mobility. That's not to say that Brandt discounts the benefits of drugs altogether. But they're more effective, he argues, when combined with lifestyle changes.

One person who is sold on a more holistic approach is Larry Nun, 56, a computer analyst who lives in Franklin, Ind. Nun first noticed the soreness around his kneecaps when he was still in his 30s. A couple of accidents, one of which required surgery to repair torn cartilage, didn't help matters. Ten years ago, Nun, who stands 6 ft. 4 in. and weighs 345 lbs., adopted some of Brandt's exercise routines and resolved to lose weight. (One of the most effective ways to cope with sitting for long stretches, he found, was to warm up his legs with a series of leg raises before standing.) Now Nun's knees act up only when he's not moving. "I'd say I've been able to control it," he says. "And I know it's not getting worse."

Meanwhile, a lot of effort has gone into figuring out how to replace damaged cartilage. Many arthritis sufferers swear by the dietary supplements glucosamine and chondroitin. Preliminary studies suggest that they may relieve pain, but the jury's still out on whether they actually promote the growth of new cartilage. The first approved biotech cartilage implants have hit the inevitable stalemate: once the new cartilage is in place, it's subject to the same destructive forces that chewed up the original cartilage. In addition, transplanted cartilage does not seem to adhere very well to existing tissue, though researchers are trying new approaches to get around that problem.

Sometimes surgery is unavoidable. Each year doctors in the U.S. perform 270,000 knee replacements and 170,000 hip replacements. So many patients have benefited that a lot of people, like Mike Ditka, 63, the Chicago Bears' Hall of Fame tight end, have had both hips replaced. To keep his new joints in good condition, Ditka works out daily. "As you get older," he says, "whatever the complications are, they're going to become magnified a hundred times if you don't exercise."

No single approach works best for everyone. As researchers learn more about what triggers osteoarthritis, they're bound to come up with more effective treatments. As with any chronic condition, there are always some things you can't control. But there's still a lot you can do for yourself. So pay attention to those twinges. Someday, you'll be glad you did.

—With reporting by Noah Isackson/Chicago, Constance E. Richards/ Asheville and Sean Scully/Los Angeles

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