Tearing of the meniscus – a cartilage-rich, crescent-shaped pad behind the kneecap that serves as a shock absorber for in joints such as the knee – is often thought of as a runner’s risk. But meniscal tears can occur spontaneously as one grows older, too. In fact, about one in five people ages 50 to 59, and more than half of people over 70 years old, have experienced one.
And meniscal tears spell increased osteoarthritis risk. Ironically, meniscectomy – surgical removal of some or all of the meniscus to relieve this condition – further elevates a patient’s risk of developing osteoarthritis over the long haul.
Throw in all the other accumulated twists and sprains and crunches of the passing years, season with a lifelong pinch of gravity, and you’ve got the recipe for a huge serving of osteoarthritis: 27 million sufferers in the United States alone.
In a study published in Nature Medicine, Stanford immunologist Bill Robinson, MD, PhD, and his collegues have now shown how an initial insult, such as a torn meniscus, triggers a cascade of low-grade-inflammatory activities in the joint that can result in the cartilage destruction that is osteoarthritis.
This discovery is a big deal because right now there are no decent drugs to slow, halt, or reverse the course of osteoarthritis – just painkillers providing symptomatic relief as the disease worsens.
But by implicating the so-called complement cascade, an all-important “first strike” immune defense system against microbial infection, in the initiation of osteoarthritis, Robinson and his colleagues have pointed at a new new target for drugs that could cut the rug out from under osteoarthritis before it ever hits the dance floor.
“People in the field predominantly view osteoarthritis as a matter of simple wear and tear, like tires gradually wearing out on a car,” Robinson told me in an interview for my news release on his study:
Recent findings suggest that low-grade complement activation contributes to the development of degenerative diseases including Alzheimer’s disease and macular degeneration. Our results suggest that osteoarthritis can be added to this list of diseases. . . . Right now we don’t have anything to offer osteoarthritis patients to treat their underlying disease. . . . It would be incredible, for the one-third of humans over 60 who have it, to find a way to slow it down.
Robinson suggests that delivering a complement-system-impeding drug only to the affected joint might someday prove therapeutic at a much more fundamental level. (You don’t want that drug roaming around in the circulatory system, because knocking out complement willy-nilly would vastly increase infection risk.)
Discovering molecular mechanisms operating very early in the course of a chronic disease gives you a chance to monitor promising therapies long before overt symptoms manifest, which in the case of osteoarthritis probably means irreversible damage to affected joints. A few years ago I wrote about another Stanford researcher, radiologist Garry Gold, MD, who’s working on a form of MRI that can visualize osteoarthritis early on. Robinson’s and Gold’s line of work, combined, could perhaps greatly speed up the search for a cure, not a palliative, for osteoarthritis.
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