A new analysis of the UK General Practice Research Database suggests that oral bisphosphonates (drugs commonly used to prevent or treat osteoporosis) may increase the risk of esophageal. These results—published in the British Medical Journal—differ from those of a previous report that used the same database.

Osteoporosis—a condition characterized by low bone mass and deterioration of bone structure—affects an estimated 10 million Americans over the age of 50. Each year, roughly 1.5 million Americans will experience an osteoporosis-related bone fracture. These fractures commonly involve the wrist, hip, or spine but can affect any part of the body.

Bisphosphonates are a class of drugs commonly used to prevent or treat osteoporosis. When taken orally, these drugs have been linked with esophageal inflammation in some patients. Bisphosphonates that may be given orally include Fosamax® (alendronate), Actonel® (risedronate), and Boniva® (ibandronate).

Esophageal inflammation from gastroesophageal reflux disease (GERD) is known to increase the risk of esophageal cancer, but it is not known whether bisphosphonate-related inflammation also affects risk.

An article published in the Journal of the American Medical Association in August, 2010, concluded that oral bisphosphonates did not significantly increase the risk of esophageal cancer. The study was based on an analysis of the UK General Practice Research Database.

Now a second study has also used this database to evaluate the relationship between oral bisphosphonates and esophageal cancer risk. This more recent study used a different study design and had longer follow-up (average duration of patient follow-up was 7.7 years in the current study compared with 4.5 years in the previous study).

In addition to collecting information about esophageal cancer, researchers collected information about gastric (stomach) and colorectal cancers. This allowed the researchers to test the idea that bisphosphonates increase the risk of esophageal cancer but do not affect the risk of other cancers of the digestive system.

The current analysis involved men and women age 40 or older. Information was available for 2,954 people with esophageal cancer, 2,018 with gastric cancer, and 10,641 with colorectal cancer. Information was also collected about a large group of people without cancer.

  • Compared with people with no prescriptions for an oral bisphosphonate, people who had one or more prescriptions were 30% more likely to have esophageal cancer. People who had 10 or more prescriptions for an oral bisphosphonate had an almost twofold increase in risk of esophageal cancer.
  • Oral bisphosphonates did not appear to affect the risk of gastric or colorectal cancer.

To put the twofold increase in risk of esophageal cancer in perspective, the five-year risk of esophageal cancer among people aged 60-79 would be roughly one case per 1,000 people among non-users of oral bisphosphonates and roughly two cases per 1000 people among those with five years of oral bisphosphonate use.

The researchers note that these findings will need to be confirmed by other studies. In the meantime, an accompanying editorial notes that “doctors should tell patients to report difficulty in swallowing and throat, chest, or digestive discomfort so that they can be promptly evaluated…”

References:


Cardwell CR, Abnet CC, Cantwell MM, Murray LJ. Esposure to oral bisphosphonates and risk of esophageal cancer. Journal of the American Medical Association. 2010;304:657-663.

Green J, Czanner G, Reeves G et al. Oral bisphosphonates and risk of cancer of oesphagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. British Medical Journal [early online publication]. September 2, 2010.

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