Hyaluronic acid exists naturally in the fluids that bathe the joints, where it acts like a shock absorber and lubricant. People with osteoarthritis -- the common, "wear-and-tear" type of arthritis -- seem to have lower-than-normal levels.

So one treatment for arthritis patients is to get injections of hyaluronic acid directly into the affected joint, a therapy also known as viscosupplementation. In the United States, it's been approved since 1997 for knee arthritis only; in Europe, it's been used longer and for more types of arthritis.

But a new research review, published in the Annals of Internal Medicine, finds the benefits may be minimal for aching knees.

Looking at 89 past clinical trials, researchers found that overall, viscosupplementation did seem to bring pain relief to some knee arthritis sufferers -- as compared to "sham" injections or no treatment.

But when they focused on 18 larger trials (with at least a couple hundred patients), there were only "clinically irrelevant" effects, according to the researchers.

On top of that, they report, the injections can carry side effects like swelling and inflammation in the joint soon after treatment.

"We don't have evidence that viscosupplementation works, but it is associated with an increased risk of adverse events," said Dr. Peter Juni from the University of Bern in Switzerland, who worked on the study.

"That is not very reassuring," Juni told Reuters Health. He and his colleagues recommend that the injections "be discouraged" for people with knee arthritis.

But an orthopedic surgeon not involved in the study said hyaluronic acid injections should still be an option for at least some patients.

"I think patient selection is key," said Dr. Joseph Bosco, from the NYU Langone Medical Center in New York.

The injections are more likely to help someone with mild to moderate knee arthritis and "no big pieces of cartilage floating around in the joint," according to Bosco. (Osteoarthritis occurs when the cartilage cushioning the ends of the bones begins to break down.)

Bosco also pointed to the limitations of the new study.

It's what researchers call a "meta-analysis," which means the results of different studies are pooled together. The issue, Bosco said, is that the individual studies differ from each other -- in how they are done, the specific hyaluronic acid formulations and characteristics of the patients.

"I think it's difficult to make an overarching comment on the use of hyaluronic acid, based on this," Bosco said.

In general, the evidence on hyaluronic acid is not high-quality, according to Dr. John Richmond, who chaired the committee that devised the current treatment guidelines on knee arthritis from the American Academy of Orthopedic Surgeons.

But he agreed the therapy should remain an option. "It's a reasonable way to manage pain" for at least some people, Richmond, also the head of orthopedics at New England Baptist Hospital in Boston, said in an interview.

MANY OPTIONS, NO SURE THING

In the early stages of knee arthritis, people may be able to go with non-drug options alone, like exercise or, if needed, weight loss. And pain relievers such as acetaminophen might help.

But when that no longer works, people often arrive at a place where they are "stuck," Richmond said.

Most commonly, they turn to non-steroidal anti-inflammatory drugs (NSAIDs) -- painkillers like ibuprofen, naproxen and the prescription drug celecoxib (Celebrex).

But both Richmond and Bosco pointed out that regularly using those drugs has significant downsides, such as stomach irritation in some people.

Injections of cortisone, which fight inflammation, can bring a temporary reprieve. But those should not be done repeatedly, Richmond said.

The final resort is surgery to replace part or all of the damaged knee joint. But, Richmond and Bosco said, that may not be appropriate for younger, more active people.

"Hyaluronic acid is no panacea," Bosco said. But, he added, "I think it should be kept in physicians' armamentarium" against knee arthritis."

In the U.S., the injections are approved for knee arthritis that cannot be managed with non-drug tactics and simple analgesics like acetaminophen or topical rubs.

When they work, the injections -- which involve anywhere from one to five separate shots, depending on the formulation -- offer only temporary pain relief. You might feel better for a few months, then need a repeat round of shots.

Based on what's known so far, repeated rounds of treatment appear safe, Richmond said.

But that gets pricey. With all costs and fees considered, one round of treatment approaches $1,000, according to Richmond. (In the U.S., Medicare and many private insurers will at least partly pay.)

As for safety, some studies in the current review looked at "serious adverse events" -- including life-threatening conditions or problems severe enough to land someone in the hospital.

Only eight studies actually described those events, which were more common in viscosupplementation patients -- 26 suffered serious problems, versus 14 patients in the untreated groups.

But those "events" included cases of cancer, cardiovascular disease and musculoskeletal disorders. And Bosco and Richmond both doubted those problems could be pinned on hyaluronic acid injections.

The trials typically lasted four months. Attributing something like cancer to the injections "doesn't make a whole lot of sense," Richmond said.

Juni said there is an "unfortunate" lack of both safe and effective options for people with knee arthritis. But he also urged people with the condition to "not be too pessimistic."

He said the basic approaches to knee arthritis, like exercise therapy and losing excess weight, can help ease symptoms in many people, if they stick with them.

The study was funded by the Arco Foundation, a private research organization.

SOURCE: bit.ly/atTzv0 Annals of Internal Medicine, online June 11, 2012.

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