The use of oral bisphosphonates was not associated with esophageal or gastric cancer in a large cohort study in the United Kingdom, according to a large U.K. database analysis.
Oral bisphosphonates cause serious esophagitis in some users. Reflux esophagitis is a known risk factor for esophageal cancer, but it is not known whether bisphosphonates-associated esophagitis also predisposes patients to develop gastric cancer, said Chris R. Cardwell, Ph.D., of Queen's University Belfast (Ireland), and his associates.
“The U.S. Food and Drug Administration recently reported 23 cases of esophageal cancer (between 1995 and 2008) in patients using the bisphosphonate alendronate and a further 31 cases in patients using bisphosphonates in Europe and Japan, possibly indicating risk of malignancy,” the investigators noted.
They searched for a possible link between the drugs and esophageal or gastric cancer using the General Practice Research Database (GPRD), “the world's largest computerized database of anonymized longitudinal patient records,” which includes 500 general practices and covers about 6% of the population in the United Kingdom.
The investigators reviewed the records of 41,826 patients aged 40 years and older who used bisphosphonates and the same number of control patients matched for age, sex, and medical practice.
During a mean follow-up of 4.5 years, 287 of these patients developed esophageal or gastric cancer.
There were no significant differences between cases and controls in risk for esophageal cancer, gastric cancer, or both cancers combined.
This result did not change when the data were adjusted to account for possible confounders of gastric cancer risk, such as smoking, alcohol use, and use of drugs including NSAIDs, proton pump inhibitors, and H2 receptor antagonists.
Moreover, the risk of these cancers was no higher in patients who took larger daily doses of bisphosphonates or in those who had a longer duration of bisphosphonate use, the investigators said (JAMA 2010;304:657-63).
In addition, the risk of gastric cancer was not significantly different between men and women exposed to bisphosphonates, and it did not differ across several different bisphosphonate medications.
There also was no association between cancer risk and bisphosphonate use in the subgroup of patients who had a history of gastroesophageal reflux disease.
Previous studies of this issue were limited by very small numbers of cases and short follow-up, lack of adjustment for potential confounders, and lack of differentiation between bisphosphonates by type, dosage, or duration of use, Dr. Cardwell and his associates noted.
“In conclusion … we found no evidence for a substantially increased risk of esophageal (or gastric) cancer in persons using oral bisphosphonates.
Access to the GPRD database was funded by the Medical Research Council.
Dr. Cardwell reported no financial conflicts of interest.