Arthritis patients taking strong painkillers, known as opioids, have a greater risk of fractures, cardiac trouble and even dying compared with those taking other forms of pain medication. But that risk varies depending on which opioid you take, according to two studies in Archives of Internal Medicine.

“Opioids were a lot riskier than one would have anticipated,” explains lead author Daniel Solomon, MD, an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital in Boston.

The first study followed 12,840 osteoarthritis and rheumatoid arthritis patients on Medicare to compare the safety of three types of analgesics: nonsteroidal anti-inflammatory drugs, or NSAIDS, such as aspirin or ibuprofen; COX-2 inhibitors like Celebrex; and opioids like oxycodone and hydrocodone.

Researchers say the most surprising finding was that fractures happened in 101 of every 1,000 opioid users per year – compared with just 19 of 1,000 COX-2 inhibitor users per year. Opioid users were four and a half times more likely to break bones than NSAID users.  

In addition, opioid patients had a significantly higher risk of dying and were more likely to have a heart attack while on the medication, compared with those on NSAIDS and COX-2 inhibitors. Currently, Celebrex is the only COX-2 inhibitor available in the United States; the other two, Vioxx and Bextra, were pulled from the market in 2004 and 2005, respectively, due to heart risks.

“(Our finding) seems to fit with the now current literature on opioids,” Dr. Solomon says. “The [recent] pulling of Darvocet from the market shouldn’t make us believe that other opioids are therefore safe,” he continues. “We should have concern about the safety of other opioids as well. This is an early step and we need to do more work to understand the safety of these drugs.”

A second and related study compared five types of opioids – codeine, hydrocodone, oxycodone, propoxyphene and tramadol – and used hydrocodone as the reference point. Researchers found people on codeine had a higher risk of heart attack than those on hydrocodone after six months. And people on codeine or oxycodone had the greatest risk of dying from any cause.

But some opioids seemed safer when it came to fracture risk. Compared with patients on hydrocodone, those on tramadol were 79 percent less likely to have a fracture, and those on propoxyphene were 46 percent less likely to have a fracture.

“I can’t tell you exactly why, but the point of the study is that there’s a lot of variation across the drugs,” Dr. Solomon says. “Taken in conjunction with our first study, I think it raises questions of the safety of any of the opioids.”

Jon T. Giles, MD, an assistant professor of medicine at Columbia University College of Physicians and Surgeons in New York City says it’s interesting and useful to see data directly compare adverse events for opioids against other analgesics. “The primary significance is that the risks of opioids compared to NSAIDs have been underestimated in this population,” Dr. Giles says. “Switching patients with chronic pain from NSAIDs to opioids because of concern for cardiovascular risk may not have any effect, or could possibly increase risk in older patients.”

Dr. Solomon says he still prescribes these strong painkillers, but thinks his study’s findings show the need for patients to talk with doctors about how this new data relates to them.

“We recognize there are patients that this is the only thing that gives them relief,” Dr. Solomon says. “One needs to balance the benefits with potential risks and until this day we’ve had nothing to say about their safety. I’m not saying this is the final word on their safety, but it gives us more information about their risks.”