Dr. Kelly Krohn's desk yesterday was piled with at least 30, maybe as many as 50, medical charts for arthritis patients who are taking some form of non-steroidal, anti-inflammatory drug.

And these were just the patients who were worried enough to call his Bethel Park office following reports linking popular arthritis drugs with heart disease and stroke. "If we pulled every chart of every patient," he noted wearily, "I'd be here until 3 a.m."

The scene was repeated in doctors' offices across the nation yesterday. On Monday, the National Institutes of Health suspended the use of naproxen, the pain reliever that Bayer sells over the counter as Aleve, in an Alzheimer's disease prevention trial because those taking the drug had a 50 percent greater risk of heart attack and stroke than those taking placebos.

The NIH also suspended the use of Celebrex, another popular arthritis drug, in the Alzheimer's study. Users of Celebrex didn't appear to be at higher risk of cardiovascular disease, but findings from a National Cancer Institute trial reported late last week suggested high doses of the Pfizer drug significantly increased the risk of heart disease and death.

The news about Celebrex had percolated over the weekend and was not totally unexpected, given that it is part of the family of drugs known as cox-2 inhibitors. Another cox-2 inhibitor, Vioxx, was withdrawn from the market by its maker, Merck, in September because it was shown to increase heart attack risk. Questions also have been raised recently about the third cox-2 inhibitor sold in the United States, Pfizer's Bextra.

But news about naproxen, an older drug that nevertheless remains a mainstay in arthritis treatment, sowed confusion. Prior to Monday's action, many doctors figured that if there were questions about the safety of cox-2 inhibitors, they could always fall back on the 20 other non-steroidal anti-inflammatory drugs on the market.

That's no longer the case, said Dr. Herbert Diamond, a rheumatologist and chairman of medicine at West Penn Hospital. "If you believe it all, then all the non-steroidals carry some risk," he said. Biologically speaking, if naproxen is risky when taken for long periods, so are other, similar drugs, such as ibuprofen, the drug sold over the counter as Advil.

"It's frankly hard to know what to do," Diamond admitted.

For now, abandoning all of these drugs is hardly an option, though doctors agree they may well be reviewing the cardiovascular disease risks of their patients who are taking non-steroidal anti-inflammatory drugs and emphasizing the importance of taking the pills only as prescribed.

And, of course, no patient should take any of these drugs unless they are really needed and really provide relief.

But physicians such as Krohn also see this as an opportunity to emphasize non-drug approaches to pain relief. Losing weight, exercising to improve muscle strength, and using orthotic devices and braces to improve the function of the knee joint in particular can do more to relieve arthritis pain than any drug, he said.

"We have proof that non-pill stuff works," said Krohn, director of clinical research in Mercy Hospital's medicine department. The nutritional supplements glucosamine and chondroitin sulfate also have shown promise, he added, and are the subject of an NIH clinical trial.

In contrast to Vioxx, which was withdrawn from the market, neither the Food and Drug Administration nor the drug makers have acted to halt sales of Celebrex or naproxen.

"It would be premature to say what we're going to do with either one of these drugs," FDA acting commissioner Lester Crawford said yesterday on NBC's "Today" show. "However, we will keep all regulator options open and make some determinations as quickly as possible."

For Charlene Phillips, 57, of Penn Hills, who has been taking Celebrex for several years, the fact that the drugs remain on the market is enough to ease her mind. Celebrex has reduced the pain of her knee osteoarthritis while supplements of Tylenol and the use of a cane help her handle flareups.

"Celebrex has not been taken off the shelf yet," said Phillips, a network coordinator for Verizon. "Until they do, I'll just sit tight."

Non-steroidal, anti-inflammatory drugs, particularly naproxen and ibuprofen, are widely used for relief of headaches, muscle aches and other pain. But the cardiovascular disease risks thus far appear to be associated only with long-term, high-dose use of these drugs ---- a concern for chronic users, such as arthritis patients, but not for people who occasionally use them for headaches or other pain.

The FDA emphasizes that the label instructions for over-the-counter Aleve, for instance, recommend that the maximum dose not exceed 220 milligrams twice daily and not be used for more than 10 days without consulting a physician.

Though print and television advertising for prescription Celebrex might imply that the drugs are better at relieving pain than other drugs, cox-2 inhibitors actually are no more potent than other non-steroidal anti-inflammatory drugs, Diamond noted. The advantage of cox-2 inhibitors isn't relief of pain, but preventing gastrointestinal bleeding.

It's been difficult to assess the effects of these drugs on cardiovascular disease in part because they don't seem to have an effect until the drugs have been used for a year or more.

Also, the detrimental effects for Celebrex and naproxen showed up in trials designed to study different diseases ---- colon cancer and Alzheimer's disease respectively ---- and were not designed to take into account the long list of risk factors that affect the cardiovascular system, such as smoking, hypertension, high cholesterol levels, lack of exercise and age, said Dr. Terence Starz, a rheumatologist at the Unversity of Pittsburgh School of Medicine.

Starz said he thinks the final answer to the safety of these drugs will emerge from further analysis of these trials and from reviews of large patient databases.

A study of 1.4 million patients in the Kaiser Permanente health system in California who took some type of prescription non-steroidal anti-inflammatory drug from 1999 through 2001, for instance, found that Vioxx increased the risk of heart attack or sudden death by about 40 percent, while those taking Celebrex actually had a decreased risk. Users of naproxen and ibuprofen were at increased risk, though less than the Vioxx users, Starz said.

All of these drugs only treat the symptom of pain, rather than addressing the cause of arthritis, noted another Pitt rheumatologist, Dr. Kent Kwoh. And all drugs, he emphasized, carry some risk. So, in the long run, the best hope may be to find a way to directly treat or prevent the disease.

Despite the common misperception, osteoarthritis is not simply a consequence of wear and tear, but results from structural and metabolic changes in the joint. Kwoh is the lead investigator locally for the Osteoarthritis Initiative, a national effort to identify biomarkers that can help identify and quantify these changes in people with knee osteoarthritis.

Once these biomarkers are identified, it should be possible to develop drugs or other therapies that can prevent, halt or reverse the process that causes osteoarthritis, he said.

Like Krohn, Kwoh emphasizes that arthritis sufferers also can get relief without drugs. "We know that exercise is good and weight loss is good," he said.

"But it takes hard work by the patient and more time by the doctor" to pursue these lifestyle prescriptions, added Krohn. "It's easier to write a Celebrex prescription."