Older people who take heartburn drugs such as Nexium, Prilosec, Prevacid and Protonix for long periods have a significantly increased risk of hip fractures, possibly because the drugs block calcium absorption, Pennsylvania researchers reported today.
The drugs, which block production of acid in the stomach, are among the most widely used in the United States, with combined annual sales of more than $10 billion.
"The perception is that the drugs are completely safe, and doctors dispense them without thinking too much about the risks and the benefits," said Dr. Yu-Xiao Yang of the University of Pennsylvania School of Medicine, who led the study published in the Journal of the American Medical Assn.
Physicians should be aware of the potential risk, prescribe the lowest possible dose and use the drug only on patients who really need it, he said.
Annually, an estimated 300,000 Americans older than 65 suffer hip fractures, according to the National Institutes of Health, and recovery is difficult. About 20% die of complications and another 20% are permanently consigned to nursing homes after their injuries.
The findings are interesting but do not prove that the drugs caused the increased risk, said Dr. Alan Buchman of Northwestern University. "Maybe they have some other problem that increases the risk for fractures," he said.
And even if the drugs are at fault, the solution may be simply to consume more calcium, either in the form of dairy products or as supplements, said Buchman, who was not involved in the study. "The average North American doesn't get enough calcium anyway," he said.
Drug manufacturers noted that the products had been used for more than 10 years and had been through many clinical trials without evidence of risk.
Spokeswoman Amy Allen of Prevacid manufacturer TAP Pharmaceuticals Inc. in Lake Forest, Ill., said the company had an extensive post-marketing surveillance system and had "not identified a safety signal for bone fractures related to Prevacid."
Yang and his colleagues used a large British database to identify 13,566 hip fracture patients older than 50 and a matched group of 135,386 healthy people.
They found that one year of using the drugs increased the risk of hip fractures by 44%. Long-term users who received high doses of the drugs had as much as 260% the normal risk. Men using the drugs had about twice the risk of hip fractures as did women, perhaps because women are more likely to take calcium supplements (for post-menopausal therapy).
Patients taking a different class of acid inhibitors that includes Tagamet, Zantac, Pepcid and Axid had a 21% increased risk of fractures after one year.
The findings are similar to those of a smaller Danish study reported this year, Yang said. In that study, however, the risk did not appear to increase with prolonged use or higher doses of the drugs.
Adequate levels of acid are required in the duodenum, the first part of the small intestine, to dissolve calcium salts so that they can be absorbed by the body, said Yang, who has received funding from several manufacturers. Studies in animals have suggested that the acid blockers can interfere with this process.
What's needed now, Buchman said, is a study that looks directly at bone mineral density to determine whether it decreases in patients receiving the drugs.
The study was funded by the National Institutes of Health and the American Gastroenterological Assn./GlaxoSmithKline Institute for Digestive Health.