People taking certain types of heartburn drugs - including Prilosec, Nexium and Prevacid - are more likely to fracture a hip, compared with people who don't take the drugs, the Associated Press reported December 27. The study involved more than 145,000 adults over the age of 50. People who used a drug called a proton-pump inhibitor for more than one year increased their risk of hip fracture by 44%, the AP reported. The study appears in the December 27 issue of the Journal of the American Medical Association.

By Robert H. Shmerling, M.D.
Harvard Medical School

What Is the Doctor's Reaction?

A newly published study suggests that a common type of treatment for heartburn may increase the risk of hip fracture. That's cause for concern, but it's too soon to say how important these findings are.

Researchers from the University of Pennsylvania School of Medicine assessed the use of proton pump inhibitors (PPIs), such as omeprazole (Prilosec) or esomeprazole (Nexium), among more than 13,000 people over age 50 who had suffered a hip fracture. They did the same thing for more than 135,000 otherwise similar adults who had never had a hip fracture. There were more PPI users among those with hip fracture, suggesting that the medication might increase the risk of hip fracture. For those taking a PPI regularly for at least one year, the risk of hip fracture was 44% higher than for those not taking a PPI. The risk was even higher for individuals taking the highest doses of PPIs for the longest amount of time.

While these findings make PPI use sound risky, this type of study can produce results that are misleading. By analyzing medication use among people who already had a hip fracture, this study cannot conclude that PPIs actually caused the hip fractures. That's why you see phrases like "associated with hip fracture" rather than "caused hip fracture" in news releases about this research.

In fact, PPI use might have no effect on the risk of hip fracture, despite the headlines you will read. That's because the findings of this study might be explained by something else, such as diet or another medication.

For example, people with severe heartburn - those who are most likely to take PPIs regularly - might change their diet to lessen their heartburn. Perhaps these changes cause them to get less calcium and vitamin D. That could increase the risk of hip fracture, too. So, a difference in diet among PPI users (rather than the heartburn drugs themselves) could account for a higher risk of fracture.

Researchers try to account for factors (called "confounders") that could create the appearance of a link when none exists, but it's impossible to completely account for everything.

It's worth asking why people take PPIs in the first place. The most common reason is heartburn, also called gastroesophageal reflux disease (GERD). When acid from the stomach sloshes into the lower part of the esophagus, it may cause pain, irritation, inflammation and damage. In severe cases, a precancerous change may occur called Barrett's esophagus. This condition increases the risk of esophageal cancer. So, treatment of GERD does not just eliminate an annoying symptom – it also prevents damage and, perhaps, cancer.

People also take PPIs for "dyspepsia," which is upset stomach, distress or discomfort in the middle or upper abdomen. For these symptoms, a PPI may not be necessary, yet many people take them anyway.

What Changes Can I Make Now?

If you have heartburn, you may be able to reduce your symptoms without taking medications. For example:

• Avoid or reduce your intake of carbonated beverages, whole milk, fatty foods, coffee and chocolate. Citrus fruits, tomatoes and other acidic foods can be more irritating to the lower esophagus.
• Rather than eating 3 meals a day, eat more frequent, smaller meals.
• Elevate the head of your bed. For example, put wooden blocks under the bedposts to raise the head at least 6 inches.
• After you eat, wait at least 3 or 4 hours before you lie down.
• Don't smoke.
• Limit your alcohol intake.
• Lose excess weight.

If your symptoms are only occasional, over-the-counter medicines such as antacids, ranitidine (Zantac) or famotidine (Pepcid) can be taken as needed. If you use these medicines and your symptoms still occur 2 or more days per week, daily medication may be a good idea. Besides PPIs, prescription-strength ranitidine or cimetidine may be helpful. Talk with your doctor about your symptoms and decide together which options make the most sense for you.

If you have osteoporosis, it is particularly important to review your risk factors (such as smoking, lack of exercise, or a low intake of calcium) and to do what you can to reduce these risks. If you have low bone density (osteopenia or osteoporosis) and are currently taking a PPI, talk to your doctor about whether you can safely reduce the dose, stop it or switch to another heartburn medication.

What Can I Expect Looking to the Future?

This study raises important questions that should promote additional research. For example:

• Is the link between PPI use real, or might it be explained by some other factor, such as diet?


• If there is a direct link between PPI use and hip fractures, how does the drug increase the risk of fracture? For example, the drugs could affect bone strength by reducing calcium or vitamin D absorption in the digestive tract, or they could affect a person's balance, contributing to falls.


• What is the actual risk associated with regular PPI use? For example, a change in hip fracture risk from 1 in 1 million to 1.4 in 1 million looks small, but this is a 40% increase. A certain level of increase in risk might be acceptable in return for relief of severe heartburn symptoms.


• What is the actual risk of not taking a PPI regularly? For people with severe GERD, the risk of not taking a PPI regularly may include a reduction in quality of life due to severe symptoms, as well as a small increased risk of esophageal cancer.

When we have the answers to these questions, we'll know how worried to be about PPI use. Until then, review the findings of this new research with your doctor and figure out together whether you should be taking a PPI, what dose, how often and for how long.