Yang said that for every 1,262 elderly patients treated with the drugs for more than a year, there would be one additional hip fracture a year attributable to the drugs. For every 336 elderly patients treated for more than a year with high doses, there would be one extra hip fracture a year attributable to the drugs.

Dr. Doug Levine of AstraZeneca PLC, which makes Nexium and Prilosec, said the study does not prove that proton pump inhibitors cause hip fractures. It merely suggests a potential association, he said. Doctors need to monitor their patients for proper dosage and watch how long they take the drugs, Levine said.

Julia Ellwanger, a spokeswoman for TAP Pharmaceutical Products Inc., which markets Prevacid, said proton pump inhibitors' safety has been well-established by rigorous studies, and the new study does not prove or disprove a connection to hip fractures.

Dr. Alan Buchman of Northwestern University, who was not involved in the research, said the study should not change medical practice, since doctors already should be monitoring the bone density of elderly people taking the drugs and recommending calcium-rich diets to all patients.

"Most people are not taking enough calcium to start with," he said. He also wondered if a similar result would have been found in a sunny climate, because vitamin D from sunshine helps with calcium absorption.

Also, Buchman said it not known whether the acid-fighting drugs prevent esophageal cancer. He said the risk of esophageal cancer has been exaggerated in the marketing of these drugs.

"I think the risk has been overplayed and scared the community," Buchman said.

Heartburn medicines are heavily are advertised in "Ask your doctor about ..." commercials in this country, particularly during the evening news.

Nexium is the third biggest selling drug in the world, behind the cholesterol medicine Lipitor and blood thinner Plavix, with global sales totaling $5.7 billion last year, according to IMS Health, which tracks drug sales.

Yang and his co-authors disclosed in the paper that they have worked as consultants and received speaking fees from companies making acid-fighting drugs. The study was funded by the National Institutes of Health and the American Gastroenterological Association/GlaxoSmithKline Glaxo Institute for Digestive Health.

Men in the study had a higher drug-associated risk of hip fracture than women, possibly because women may be more aware of osteoporosis and may get more calcium in their diets, Yang said. He plans more research on whether calcium-rich diets or calcium supplements can prevent the problem.

1

2