Oral bisphosphonates associated with increased risk for esophageal cancer

Green J. BMJ. 2010;doi:10.1136/bmj.c4444.

The risk for esophageal cancer nearly doubled in patients given 10 or more prescriptions for oral bisphosphonates, and the risk associated with the drugs increased over time. The drugs were not associated with increased risk for gastric or colorectal cancer.

Researchers in the United States and Europe recruited 2,954 patients with esophageal cancer who were matched with 14,721 healthy controls. The mean observation period was 7.5 years.

The mean number of prescriptions for those assigned to fewer than 10 prescriptions was 3.6 vs. 21.6 for those given more than 10 prescriptions. Patients with at least one prescription were at increased risk compared with those who were not prescribed oral bisphosphonates (RR=1.30; 95% CI, 1.02-1.66). The risk was significantly increased for those with 10 or more prescriptions (RR=1.93; 95% CI, 1.37-2.70).

Longer duration of bisphosphonates was similarly associated with an increased risk for esophageal cancer. Researchers segregated patients by duration of bisphosphonate use: less than 1 year, 1 to 3 years and more than 3 years. The mean duration of use for those who used bisphosphonates for more than 3 years was 4.6 years.

Compared with controls, RR for the less than 1 year group was 0.98 (95% CI, 0.66-1.46), 1.12 for 1 to 3 years (95% CI, 0.73-1.73) and 2.24 for 3 years or more (95% CI, 1.47-3.43).

Risk did not vary by bisphosphonate type.

“If confirmed, an association between use of oral bisphosphonates and risk of esophageal cancer would add to our knowledge of the risks and benefits of use of oral bisphosphonates,” Green and colleagues concluded.

These findings contrast data by Cardwell et al published in the Journal of the American Medical Association in August. After analyzing pooled data from the U.K. General Practice Research Database on more than 80,000 people, the researchers found no significantly increased risk for esophageal or gastric cancers with oral bisphosphonate use when compared with no bisphosphonate use. During a mean 4.5 years of follow-up, 116 cases of esophageal or gastric cancers occurred compared with 115 cases identified in nonusers. Among bisphosphonate users, the overall risk for esophageal cancer was 0.48 per 1,000 person-years vs. 0.44 per 1,000 person-years among nonusers. Risk for either type of cancer also did not differ by duration of bisphosphonate use.

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