Infections, fractures linked to popular acid-reducing drugs

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A class of acid-lowering drugs that is among the most widely prescribed medications in Canada appears to increase the risk of fractures in women as well as infections with the potentially deadly bacteria, C. difficile.

Back-to-back studies published this week by the journal Archives of Internal Medicine show the drugs -- proton pump inhibitors -- are associated with increased rates of spine, lower arm and total fractures in postmenopausal women, and a more than 70 per cent increase in the odds of infection with Clostridium difficile, a bacterium that causes diarrhea and other serious intestinal conditions.

The drugs have also been shown to increase the risk of pneumonia.

The widely used family of drugs include Prilosec, Nexium and Protonix as well as Losec, Zegerid, Prevacid and omeprazole.

"A staggering 113.4 million prescriptions for proton pump inhibitors (PPIs) are filled each year, making this class of drugs, at $13.9 billion in sales, the third highest seller in the United States," Dr. Mitchell Katz of the San Francisco Department of Public Health writes in an accompanying editorial. Last year in Canada, 21.1 million prescriptions for the drugs worth nearly $1.4 billion were sold by retail pharmacies, according to prescription drug research firm IMS Health Canada.

Proton pump inhibitors -- the most potent acid-suppressing drugs on the market -- are used to prevent and treat stomach ulcers, gastroesophageal reflux disease (GERD) and other conditions.

"There's no question that they work," Katz said in an interview. "They're effective and they do not have any immediate side-effects. But people have not realized the serious side-effects associated with PPIs, because they cause increased rates of common conditions."

"So when a postmenopausal woman has a fracture, she wasn't thinking, 'Gee, this is because I was taking a PPI.' She's thinking, 'It's because I'm 65.' But that PPI may have contributed to it." Katz says 60 to 70 per cent of prescriptions for PPIs are for minor problems, such as simple heartburn, "something that our grandparents might have taken bicarbonate soda for."

"Now we say, I'll just take a pill. These medicines have been aggressively promoted by pharmaceutical companies as essentially a lifestyle drug."

All drugs have risks, he said. But "in this case, people are taking a medicine that is putting them at risk for serious side-effects, and 60 to 70 per cent of the time there is no reason for them to be on the medication."

The increased risk is not thought to be caused by the drugs themselves, but by the sharply reduced levels of acid in the stomach and intestinal tract, which make the organs a more hospitable environment for infectious agents like C. difficile and which can impair the uptake of the calcium required for strong bones.

In Canada, the drugs are so "grossly overused" and widely prescribed that "we don't bat an eye when we see them on a patient's drug list," says Dr. David Juurlink a senior scientist at the Institute for Clinical Evaluative Sciences in Toronto. "We don't often consider whether or not they're actually appropriate."

In the fractures study, researchers looked at the impact of PPIs on 130,487 women, age 50 to 79, enrolled in the Women's Health Initiative study, known best for its research on hormone replacement therapy. Over eight years of follow-up, the researchers found no increase in the risk of hip fractures in women on PPIs. But they did find a 47 per cent increased risk of spinal fracture, a 26 per cent increased risk for forearm or wrist fracture and a 25 per cent increased risk of total fractures. A woman's individual risk was "modest," Katz says, but, given the widespread use of proton pump inhibitors, "that's a lot more fractures" on a population level. He said the drugs may affect the rate of bone formation versus bone breakdown.

The C. difficile study was based on an analysis of more than 100,000 patients discharged from Boston's Beth Israel Deaconess Medical Centre between 2004 and 2008. Once-a-day proton pump inhibitor use was associated with a 74 per cent increase in C. difficile infection, compared to patients not on acid-lowering drugs. Those who took a PPI more than once a day had a more than doubling of the risk. In another study involving 1,200 patients treated for C. difficile, researchers found a 42 per cent increased risk of recurrence if proton pump inhibitors were used.

Dr. Michael Howell, director of critical care quality at Beth Israel Deaconess and an instructor at Harvard Medical School, says C. difficile rates began increasing at his hospital "at about the same time we were beginning to see lots of use of proton pump inhibitors."

-- Canwest News Service / Los Angeles Times

Republished from the Winnipeg Free Press print edition May 11, 2010 A2