The FDA released a Drug Safety Communication warning about a possible risk of increased fractures with acid blocking medications called proton pump inhibitors or PPIs.

PPIs have been a major advance in medical science. Prior to these and earlier medications, the treatment for severe gastroesophageal reflux disease (GERD) was major surgery. PPIs are now commonly prescribed for GERD and less serious heart burn, many are generic, and some are now sold over the counter.

The popular PPIs include Nexium (esomeprazole), Prilosec (omeprazole), Prevacid (lansoprazole), and Protonix (pantoprazole) which are available by prescription. Prilosec OTC and Prevacid 24HR are sold over-the-counter (OTC). Given the use and popularity of these medications, this warning may cause great concern among patients who rely on these medications.

What did the FDA find?

The FDA analyzed the data from several epidemiologic studies in thousands of patients studied for several years and in 6-7 studies found a greater risk for certain kinds of fractures when patients took PPIs. These risks seemed to be the greatest when patients were taking the medications regularly, for a long time, and at a high dose.

So is this a real problem?

Maybe. It is important to know that the gold standard of studies is the randomized clinical trial (RCT). Only RCTs can prove a cause and effect. None of the RCTs with PPIs thus far have shown and increase fracture risk with PPIs. The problem with RCTs is that they are hard to do and are usually limited in time (6 months) and have fewer patients. So a rare but serious side effect is unlikely to be picked up in an RCT.

The epidemiologic studies are useful, but have limitations (which the FDA readily points out). These studies are case-control, meaning they look for people who had fractures, find similar people who didn’t have fractures, and then see how common PPI use was in each group. Though the studies show that people with fractures were more likely to take PPIs than people without fractures, this doesn’t mean that PPIs cause fractures.

Maybe the folks who took PPIs had stomach troubles and were less likely to take things that prevent fractures like calcium or bisphosphates (drugs which prevent fractures but are relatively contraindicated in those patients with GERD). In addition, these studies use claims databases.

This means that to get the data, doctors never examined or interviewed patients, rather the investigators looked at insurance claims for fractures, medication use, etc. For example, we don’t know what the bone density scores (DEXA) were for the patients in this study. It is very possible (and even likely) that the patients in the fracture group had lower DEXA scores, and this more than the PPI use accounted for fracture.

Also, if you have ever received a bill or claim notification from your insurance company, you problem know that the information they contain is not always 100% accurate. That said, the number of patients studied and the consistency of this relationship suggests that there may indeed be a cause and effect.

What should you do?

It is unlikely that short term use of PPIs substantially increase risk of fractures. So if you need an occasional Prilosec OTC, this is probably fine. If you need to take PPIs, either prescription or over the counter, on a daily basis and have symptoms when you do not take them regularly, this could be a sign of more serious disease and should be investigated by a physician (regardless of a fracture risk).

For those patients who have had an extensive medical work up for a stomach condition and told by a physician that taking a PPI on a daily basis for years to come is the recommended treatment, then they should discuss the risks and benefits of PPIs as it relates to fractures. This would be particularly important if you have an increased risk for fracture such as a previous fracture, family history of osteoporosis, or low bone density.

Matthew Mintz is an internal medicine physician and blogs at Dr. Mintz’ Blog.

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