Heart burn drugs and hip fractures in postmenopausal women smokers: Study establishes link

By Dr. Ananya Mandal, MDFeb 2 2012

A new study shows that postmenopausal women with a history of smoking who take heartburn drugs called proton pump inhibitors (PPIs) for two years or longer may be more likely to sustain a hip fracture. The risk rises with longer use say researchers. But the risk does disappear after women stop taking these drugs for two years. Further women who never smoked were not at increased risk for hip fracture even if they took PPIs regularly, the study showed. The new findings appear in the journal BMJ.

PPIs are available by prescription and over the counter. They work by reducing the secretion of stomach acid. PPIs such as Nexium, Prevacid, Prilosec, and Protonix are commonly recommended for people with gastroesophageal reflux disease (GERD), peptic ulcers, erosive esophagitis, and a precancerous condition known as Barrett's esophagus. They are among the most widely used medications worldwide.

Researchers explain that by changing the acid environment in the stomach the drugs may also reduce the absorption of calcium, which is needed for healthy bones. This is not the first study to link long-term PPI use with bone fractures, but it does help narrow down who is at greatest risk.

The team from Harvard Medical School and Massachusetts General Hospital in Boston looked at data spanning nearly 20 years involving 80,000 women who had been through the menopause.

Every two years they were asked how often they had taken these drugs and whether they had suffered any hip fractures.

Postmenopausal women with history of smoking who take PPIs for longer than two years have more than a 50% chance of sustaining a hip fracture, says researcher Hamed Khalili. He is a gastroenterologist at Massachusetts General Hospital in Boston. It is also time to take a long, hard look at who is taking these pills chronically and why. “There are very few indications that require long-term and regular use of PPIs,” he says. He advises, “Consider stopping if there are no real indications, and among those that require long-term use, you may try to switch to less potent acid-suppressive medications.” For every 500 patients on the drugs only one would be likely to fracture their hip in a year he says.

Tobie de Villiers, president of the International Menopause Society, says, “Although the relative risk of hip fracture is significantly raised in users of PPIs when compared to non-users, the absolute risk increase is small. This is still important in view of the widespread use of PPIs and the significant burden of hip fractures on affected individuals and the healthcare system.”

Robynne Chutkan adds that these medications must be used judiciously, not indiscriminately. She is an assistant professor of medicine at Georgetown University Hospital in Washington, D.C. She says “the cornerstone treatment for GERD is still lifestyle modifications.”

This includes decreasing alcohol and caffeine intake, quitting smoking, improving eating schedules especially dinner time and lose excess weight. “These drugs are so effective that people are less compelled to change their habits, but their use comes with a price - fracture risk,” she says.

Ethel S. Siris, agrees that long-term PPI use is another risk factor for fractures, especially in women with a history of smoking. She is the Madeline C. Stabile Professor of Clinical Medicine and the director of the Toni Stabile Osteoporosis Center at Columbia University Medical Center in New York. “The bottom line is that this is one more risk factor that you have to work around,” she says. “If the woman has already had a fracture, it is time to consider medication to prevent repeat fractures,” Siris says.

Dr John C Stevenson, Consultant Physician and Reader, at the Royal Brompton Hospital, says, “It has been suspected for a number of years that a certain type of indigestion pills, proton pump inhibitors, increases the risk of hip fracture. This large study confirms that suspicion. However, the absolute risk is small, with the drugs causing an additional five hip fractures per 10,000 women per year. Women should not be put off using proton pump inhibitors if they are needed, but these results provide yet another reason not to smoke.”

The Harvard study only involved women, but other research suggests that men taking these drugs are also at risk. One by Canadian scientists on both men and women in 2008 found that those who had taken the drugs for five years were 44 per cent more likely to have a hip fracture.

Dan Greer, spokesman on gastroenterology medicines at the Royal Pharmaceutical Society, says, “This is a useful study that has taken account of the other factors that can affect hip fractures such as smoking, calcium intake, and obesity that has been missing from other studies looking at the link between PPIs and hip fracture. It suggests there may be a small increase in hip fracture risk associated with these medicines in a high-risk group. Women should be reassured though that the absolute risk is small.”

In May 2010, the U.S. Food and Drug Administration warned of hip fractures among those taking PPIs but concluded that more data was needed for a full analysis. The study was funded by the U.S. National Institutes of Health.