You may find that walking into a drugstore and buying a medicine to deal with a symptom is easier than scheduling an appointment to discuss what is going on with your doctor. It is! The challenge is to be a well-informed healthcare consumer. Sometimes you may plan on taking a medicine temporarily, but end up taking it long-term instead. You may forget to include the over-the-counter medicine in your list or bag of medicines when you do make it to the doctor.
Many people with heartburn or gastroesophageal reflux disease (GERD) medicate themselves with over-the-counter drugs. As you walk down the drugstore aisle, you have a variety of choices to battle stomach acid. You might choose antacids, such as Tums, or more powerful medicines such as Zantac®, Pepcid®, Prevacid, Prilosec, or Zegerid®. You may choose the generic store brand equivalents. The branded products are advertised widely, so the names may be familiar to you from your magazines or from television commercials. Zantac and Pepcid are classified as histamine2-receptor antagonists (H2 blockers); Prevacid, Prilosec, and Zegerid are proton pump inhibitors (PPIs).
Why am I making the distinction? Because recent major research studies have connected the use of PPIs to an increased risk of fractures, especially hip fractures. Both H2 blockers and PPIs work by reducing stomach acid secretion. The H2 blockers affect the first step of acid secretion by blocking the histamine of the acid-producing cells and about 70 percent of stomach acid production. Proton pump inhibitors block the proton pump, which is the last step of acid production by the stomach. As a result, PPIs suppress up to 99 percent of stomach acid and are more potent than the H2 blockers. Therefore, PPIs are prescribed more often than the older, less effective H2 blockers.
The availability of PPIs on the drugstore shelves is growing as well. Lower dose formulations of Prilosec, Prevacid, and Zegerid are available over-the-counter (OTC) without a prescription. The FDA approved these OTC treatments for frequent heartburn. In addition, one prescription pain reliever, Vimovo®, now contains esomeprazole in combination with naproxen, a nonsteroidal anti-inflammatory drug (NSAID), to lessen the risk of stomach upset or ulcers.
Proton Pump Inhibitors “PPIs”
| Brand Name | Generic Name |
| Aciphex® | rabeprazole |
| Dexilant™ (formerly Kapidex®; name changed 2010) | dexlansoprazole |
| Nexium® | esomeprazole |
| Prevaci® | lansoprazole |
| Prilosec® | omeprazole |
| Prilosec® | omeprazole |
| Protonix® | pantoprazole |
| Zegerid® (brand production for prescription strength stopped in 2010 when patents were ruled invalid. A lower strength generic is available OTC.) | omeprazole |
PPIs are now among the most widely prescribed class of medicines. In 2010, PPIs ranked eighth in number of prescriptions written in the US. The brand Nexium was number two in sales of all prescription drugs, generating $6.3 billion—just behind the cholesterol-lowering drug Lipitor.®
Millions of Americans are taking PPIs as prescription and OTC medicines.
PPIS AND FRACTURE RISK
Two research groups first reported the link between PPIS and fracture risk in 2006. Examining the British General Practice Research Database of more than 1.7 million persons, researchers reported that PPI therapy was associated with an increased risk (44 percent higher) of hip fractures. Risk increased with longer duration of use, and the highest risk was seen among those receiving high-dose PPI therapy. A large Danish study reported a similar magnitude of risk increase for hip fracture and a small increase (18 percent) in risk for all fractures.
Subsequent studies found similar results. A database analysis from the Canadian province of Manitoba observed that residents who suffered an osteoporosis-related fracture were almost twice as likely to have used a PPI for at least seven years. For hip fracture, there was an increased risk of fracture after five or more years of use. Using PPIS for fewer years was not linked to increased fracture risk.
In the US, researchers from the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF) found that use of PPIS in older women, as well as in older men with low daily calcium intake, was associated with an increased risk of nonspine fractures. Based on the women's results, the SOF researchers estimated that one extra nonspine fracture would be expected for every ten women treated for five years with a PPI. While this represents a small individual risk, given the widespread use of these medicines, the numbers for the US population as a whole are large.
The link between long-term use of proton pump inhibitors and greater likelihood of osteoporosis-related fractures of the hip, wrist, or spine is based on observational studies. This type of study describes the association but does not prove cause and effect. A clinical trial would be needed to establish causality without a doubt. In the future, it is unlikely such trials will be undertaken to try to show a harmful outcome.
POOR CALCIUM ABSORPTION
One plausible explanation for the link between PPIS and increased fracture risk is that PPIS may affect calcium balance by decreasing calcium absorption in the small intestine. Hydrochloric acid is needed for the absorption of calcium in the small intestine. Since proton pump inhibitors inhibit the production and secretion of hydrochloric acid in the stomach, calcium may not be dissolved or adequately absorbed from food or supplements. Because users of PPIS tend to take them for a long time, this could lead to a negative whole-body calcium balance, resulting in higher rates of bone loss and a greater risk of fractures.
If this is true, could adequate amounts of calcium intake diminish the observed adverse bone effects of PPI use? It is not known. However, you should be vigilant to ensure that your daily diet and supplements contain 1,000 to 1,200 mg of calcium. It is also important to remember that adequate vitamin D intake is necessary for maintaining a blood level of 30 ng/ml or greater for your body's ability to absorb calcium.
CALCIUM SUPPLEMENTATION: DOES IT MATTER?
Calcium Carbonate versus Calcium Citrate
I usually recommend taking calcium citrate when you are taking medicine to suppress acid, but studies to fully address the choice of a calcium supplement if you are taking long-term PPI therapy have not been done.
Calcium carbonate requires acid for dissolving while calcium citrate does not. Usually, you take calcium carbonate with or after a meal, but the timing of calcium citrate does not matter.
When older women volunteers who used Prilosec 20 mg daily for two weeks took calcium carbonate on an empty stomach after fasting overnight, calcium absorption was significantly decreased. It is unclear whether absorption is normal if calcium carbonate is taken with a meal, which is when it should be taken. Calcium carbonate and calcium citrate have not been compared when taken with a meal in people receiving PPI therapy.
Some experts base their recommendations for calcium on indirect evidence from studies in patients who do not produce acid. These patients can absorb calcium carbonate when taken with a meal. This suggests that taking calcium carbonate during meals should work.
However, my interpretation, based on the best available evidence regarding the choice of a calcium supplement, is that you should take calcium citrate at mealtime for good measure along with increasing calcium in your diet.
BALANCE BENEFITS OF PPIS AND RISK OF FRACTURE
Based on fracture risk alone, I would not recommend stopping a PPI if you need it. However, your risk of fracture should be assessed in conjunction with the “whole picture” of all other risk factors. If you already have low bone mass, you should talk with your doctor about strategies to lower your fracture risk. Reassess with your doctor the indication for taking the medicine and reason for continuing its use. You may consider:
- lowering your dose of PPI medicine
- changing to another non-PPI medicine
- temporarily stopping the PPI medicine to see if you still need it
- using PPI medicine only when symptoms occur
In addition, make sure you are taking an absorbable calcium supplement and adequate vitamin D.
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The Bare Bones
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