Bisphosphonates and Esophageal Cancer

What is the concern?

Researchers have been looking into a possible link between the use of oral bisphosphonate medications, such as alendronate (Fosamax®), ibandronate (Boniva®) and risedronate (Actonel®) and an increased risk of esophageal cancer. Bisphosphonate medications are prescribed to reduce the risk of fractures (broken bones).

What do we know?

Two studies were recently conducted in the United Kingdom (U.K.). The first study, published in the Journal of the American Medical Association (JAMA), did not show an increased risk of esophageal cancer in people taking oral bisphosphonates or in people taking oral bisphosphonates for longer than three years. The second study, published in the British Medical Journal (BMJ), suggested a potential increase in the risk of esophageal cancer in people taking oral bisphosphonates for about five years or more. These two studies from the same large population of patients in the U.K., used different study designs and methods to investigate the potential link between bisphosphonates and esophageal cancer.

The JAMA study, showing no increased risk, looked at people with and without exposure to oral bisphosphonates and followed them for an average of four years (over a span of time). The BMJ study, showing an increased risk, looked at patients diagnosed with esophageal cancer, matched each patient with other patients who did not have esophageal cancer and noted that those with esophageal cancer were more likely to have had greater exposure to oral bisphosphonates. TheBMJ study did not have a clear and definite measurement of the actual length of bisphosphonate therapy. Neither study was able to determine if the bisphosphonates were taken correctly and as prescribed. In general, there needs to be further study of the association between bisphosphonates and esophageal cancer.

Guidance for patients

If you take oral bisphosphonates or are considering treatment with oral bisphosphonates you should do the following:

• Discuss your concerns about bisphosphonates or any other medicine with your healthcare provider
• Review your individual risk factors for esophageal cancer, which include tobacco use, excessive alcohol use, obesity, Barrett's esophagus, radiation treatment to the chest or upper abdomen and other problems associated with the risk of esophageal cancer
• If you are taking oral bisphosphonates, take the medicine exactly as directed to reduce the chances of esophageal irritation
• Report any unusual symptoms, such as gastric reflux, painful or difficulty swallowing or other symptoms to your healthcare provider and discuss appropriate steps to take with regard to your treatment

There is no indication that concerns about esophageal cancer apply to intravenous (I.V.) forms of bisphosphonate medications.

Summary

The finding of no association in the JAMA study is consistent with two other studies, one using a U.S. patient population and the other using a Denmark patient population. None of the studies determined if the bisphosphonates were taken as prescribed. There are FDA-approved osteoporosis medications besides oral bisphosphonates for persons with risk factors for esophageal cancer. Individuals are advised to discuss their concerns and treatment options with their healthcare professional.

Serious long-term disability and death are significant consequences of osteoporotic fractures. Bisphosphonates have been shown to reduce the risk of fractures in individuals with osteoporosis. For this reason, NOF believes the benefits of bisphosphonate treatment in patients at risk of osteoporotic fracture strongly outweigh the risks from treatment for most individuals. As with all medications, the risks and benefits of treatment must be carefully considered.

References

Abrahamson B, Eiken P, Eastell R. Correspondence: More on Reports of Esophageal Cancer with Oral Bisphosphonate Use [Letter to the Editor]. NEJM. 2009 Apr 23; 360(17): 1789-1792.

Cardwell CR, Abnet CC, Cantwell MM, Murray LJ. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA. 2010 Aug 11;304(6):657-63.

Green J, Czanner G, Reeves G, Watson J, Wise L, Beral V. Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort.BMJ. 2010 Sep 1;341:c4444.

Solomon DH, Patrick A, Bookhart MA. Correspondence: More on Reports of Esophageal Cancer with Oral Bisphosphonate Use [Letter to the Editor]. NEJM. 2009 Apr 23; 360(17): 1789-1792.