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.
The risks are relatively small, but the drugs are so widely used that large numbers of people are affected, wrote Dr. Mitchell H. Katz of the San Francisco Department of Public Health in an editorial accompanying the reports, which were published in the Archives of Internal Medicine. Katz noted that 113.4 million prescriptions for the drugs, known as proton pump inhibitors, are written each year, and large numbers are sold without prescriptions.
Although the drugs have many valuable uses, Katz said, "for most patients, the adverse effects of [proton pump inhibitors] outweigh the benefits."
The family of drugs, which also includes Losec, Zegerid, Prevacid and omeprazole, is widely used to treat conditions in which excess stomach acid causes pain and bleeding, including ulcers, and gastroesophageal reflux disease, in which stomach acid is regurgitated into the esophagus. But the drugs are also widely used to treat simple heartburn, and that is the condition for which they are most widely overused, experts said.
"Harm will result if these commonly used medications are prescribed for conditions for which there is no benefit, such as non-ulcer dyspepsia [heartburn]," Dr. Deborah Grady and Dr. Rita F. Redberg of UC San Francisco said in another editorial.
Among the findings of the reports:
- Pharmacologist Shelly L. Gray of the University of Washington and her colleagues studied 130,487 women in the Women's Health Initiative. After an average of eight years of follow-up, they found a 47% increase in spinal fractures and a 26% increase in forearm and wrist fractures but no increase in hip fractures. Overall, the increased risk of fractures was 25%.
- Dr. Michael D. Howell of Beth Israel Deaconess Medical Center in Boston and his colleagues studied more than 100,000 patients discharged from hospitals over a five-year period. They found that incidence of infection with C. difficile increased with increasing doses of proton pump inhibitors. The hard-to-treat bacterium causes severe diarrhea and other medical problems and can be deadly if not properly treated. About 0.3% of those who received no proton pump inhibitors during their stay contracted C. difficile infections, whereas about 1.4% of those taking the most powerful drugs at least twice a day contracted the bacterium, a 366% increase.
- Dr. Amy Linsky of Boston Medical Center and her colleagues studied 1,166 patients being treated for C. difficile infections. They found that 25.2% of those who were taking proton pump inhibitors suffered a recurrence of their infection, compared with 18.5% of those who were not taking the drugs, a 36% increase in risk.