TORONTO - Long-term treatment with one class of drugs used to treat acid reflux and peptic ulcers has been linked to an increased risk of osteoporosis-related fractures, say Canadian researchers, who suggest the widely used medications are often inappropriately prescribed.
Their study, published this week in the Canadian Medical Association Journal, found that those who took the drugs for five years almost doubled their risk of hip fractures compared with people not taking the medications.
Furthermore, staying on the prescription drugs continuously for seven or more years resulted in a more than four-fold greater risk of fracture, said lead investigator Dr. Laura Targownik, a gastroenterologist at the University of Manitoba.
The drugs, which are known as proton pump inhibitors and include the brand names Prilosec, Nexium and Prevacid, treat acid reflux and heal and prevent peptic ulcers by reducing the production of hydrochloric acid in the stomach.
Hydrochloric acid is believed to play an important role in the body's absorption of calcium, which is needed for strong bones.
However, Targownik said the study does not prove that antacids like Prevacid cause the bone-thinning that can lead to fractures.
"At this point, I'd say it's an association," she said Monday from Winnipeg. "There are a number of potential reasons why proton pump inhibitors might have this effect, but we need to do further research to answer those questions."
To conduct the study, the researchers used administrative claims data in Manitoba to identify almost 16,000 patients 50 and older who had suffered a fracture of the hip, vertebra or wrist between April 1996 and March 2004. They were compared to more than 47,000 controls without such fractures, and the two groups were assessed for PPI use over the study period.
Proton pump inhibitors are widely used in Canada. More than 10 million prescriptions are written for the drugs each year, according to estimates.
And while PPIs are considered the best medications for treating severe acid reflux and peptic ulcers, Targownik said they are too often inappropriately prescribed.
"Someone might have very mild heartburn that could easily be managed with other medications, such as Tums or Zantac, who are prescribed a proton pump inhibitor," she said. "And then it works, but no one ever thinks of stepping down the therapy."
She said people taking anti-inflammatory drugs like ibuprofen for arthritis or daily ASA to prevent a heart attack are at risk for bleeding ulcers. Left untreated, these ulcers can lead to death from continued, unchecked blood loss.
Such patients need PPIs, Targownik said. "And there are a lot of people we know who aren't on these medications."
"However,there are also people who get prescribed these medications and don't know why. There is obviously appropriate use, but there is inappropriate overuse and inappropriate underuse."
Still, she said people taking the drugs shouldn't panic.
"I'm comfortable at this point with saying if you're only going to be on this medication a short time, don't worry. If you're going to be on it a long time, the jury's still out as to what you should do."
"If you're on one of these medications and think you may be at risk for osteoporosis or you have osteoporosis or you've had a fracture in the past, it's a good time for you to make an appointment with your doctor, to discuss why you're on these medications" and whether it's necessary to continue.
In a CMAJ commentary accompanying the study, Drs. David Goltzman and Brent Richards of McGill University say three studies using health-record analysis have now suggested a link between the drug class and bone fracture risk.
To prove that PPIs actually cause osteoporosis, different types of studies would be needed -- the most powerful being a randomized controlled trial that would compare one group taking the drug against another group given a placebo.
But in an interview Monday from Montreal, Goltzman said it would be difficult to get hospital ethics boards to approve such a study because of the potential risk of osteoporosis to those given the drug.
"I think the message is that first of all we need a different approach to try to confirm this," he said of the possible link.
"But also the message is strong enough now that patients and physicians should be aware that this is a potential harmful side-effect and these medications should not be used casually, which they sometimes are because they really don't have too many other side-effects."
