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Using data from almost 140 studies, researchers found all of the widely used arthritis treatments -- from over-the-counter painkillers to pain-relieving injections -- brought more relief to aching knees over three months than did placebo pills.
But there were some surprises in the study, according to lead researcher Dr. Raveendhara Bannuru, of Tufts Medical Center in Boston.
Overall, the biggest benefit came from injections of hyaluronic acid (HA) -- a treatment some professional medical groups consider only marginally effective.
Hyaluronic acid is a lubricating substance found naturally in the joints. Over the years, studies have been mixed as to whether injections of synthetic HA help arthritic joints, and the treatment remains under debate.
Bannuru cautioned that despite his team's positive findings, it's not clear whether hyaluronic acid itself deserves the credit.
That's because his team found a large "placebo effect" across the HA studies. Patients who received injections of an inactive substance often reported pain relief, too. As a whole, they did better than people in other trials who were given placebo pills.
But there's no clear explanation for why that would be, Bannuru said.
He and his colleagues report their findings in the Jan. 6 issue of Annals of Internal Medicine.
According to the U.S. Centers for Disease Control and Prevention, at least 27 million Americans have osteoarthritis -- the "wear and tear" form of arthritis where the cartilage cushioning a joint breaks down. The knees are among the most commonly affected joints.
In the earlier stages of knee arthritis, doctors often recommend oral painkillers like acetaminophen (Tylenol) or nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin) and naproxen (Aleve).
Injections are another option -- either with hyaluronic acid or the anti-inflammatory drug cortisone.
The problem is, few studies have actually tested any of those treatments head-to-head, Bannuru said. So it's hard to know whether one is any better than the others.
To get an idea, his team used a statistical method that allowed it to compare results from previous clinical trials that tested either oral medications or injections.
In general, the review found, all therapies were better than placebo pills at easing pain at the three-month mark. But they were not all equal.
Injections of hyaluronic acid were most effective, followed closely by cortisone. NSAIDs came in next, with acetaminophen rounding out the bottom of the list -- which is not surprising, though it is important, Bannuru said.
And because acetaminophen is less risky, it is still a "very reasonable" place to start, said Dr. Lisa Mandl, a rheumatologist at the Hospital for Special Surgery in New York City.
"However, I would suggest using a high dose for a short trial period. And if it's not effective quickly, move on to another option," said Mandl, who cowrote an editorial published with the study.
And based on these findings, she said, injections -- whether hyaluronic acid or cortisone -- could well be worth a try. That's partly because they often work, but also because they can avoid the systemic side effects of oral painkillers, Mandl said.
With injections, side effects are usually limited to temporary pain and swelling. In rare cases, people can have an allergic reaction or infection, according to the American Academy of Orthopedic Surgeons.
Bannuru said people with knee arthritis ultimately have to decide for themselves, after discussing the pros and cons of different therapies with their doctor.
And there are options beyond oral drugs and injections.
"Even though we didn't test [them] in our study," Bannuru said, "it's important for people with knee arthritis to know there are several non-drug treatments, such as exercise and physical therapy."
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SOURCES: Raveendhara Bannuru, M.D., researcher, Center for Arthritis and Rheumatic Diseases, Tufts Medical Center, Boston; Lisa Mandl, M.D., rheumatologist, Hospital for Special Surgery, New York City; Jan. 6, 2014, Annals of Internal Medicine