Back grey_arrow_rt.gif
No Cancer Risk with Bisphosphonates
  MedPage Today
Published: August 11, 2010
Action Points
* Point out that bisphosphonate use has been associated with esophagitis in some patients.
* Explain that this was a retrospective study subject to several limitations but there still was no evidence for a substantially increased risk of esophageal or gastric cancer.
Use of oral bisphosphonates did not increase the risk of esophageal or gastric cancer in a large cohort of patients followed for more than four years.
Bisphosphonate users and nonusers had similar rates of the individual cancers and of both cancers combined, according to a report in the Aug. 11 issue of the Journal of the American Medical Association.
The findings should help allay concerns about a theoretical cancer risk related to bisphosphonates' propensity to cause esophagitis in some patients, researchers Chris R. Cardwell, PhD, of Queen's University Belfast in Ireland, and coauthors noted.
Their analysis of medical records showed esophageal cancer rates of 0.48 cases per 1,000 person-years in bisphosphonate users and 0.44 cases per 1,000 person-years in nonusers.
"These drugs should not be withheld, on the basis of possible esophageal cancer risk, from patients with a genuine clinical indication for their use," they wrote in conclusion.
Widespread use of oral bisphosphonates to treat osteoporosis has shown that some patients develop serious reflux esophagitis, a known risk factor for esophageal cancer. Crystalline material resembling a bisphosphonate has been identified in patients with bisphosphonate-related esophagitis, and follow-up endoscopy showed persistent abnormalities after healing (Gastrointest Endosc. 1998;47:525-528).
Bisphosphonates' potential to cause esophageal cancer has been unclear, although the FDA has reported cases among bisphosphonate users in the United States, Europe, and Japan (N Engl J Med. 2009;360:89-90).
In an effort to assess the cancer risk in bisphosphonate users, Cardwell and colleagues analyzed records in a large database comprising 500 general medical practices. They identified all patients who received a bisphosphonate prescription from 1996 through 2006 and compiled a control group matched for age, sex, and medical practice.
Each group included 41,826 patients, 81% of whom were women and whose mean age was 70.
During a mean follow-up of about 4.5 years, 116 esophageal and gastric cancers occurred in the bisphosphonate cohort and 115 in the control group.
The combined incidence of esophageal and gastric cancer was 0.7 per 1,000 person-years in both groups.
The totals included 79 esophageal cancers in the bisphosphonate users and 72 in the control group, a nonsignificant difference.
Further analysis showed no difference in rates of esophageal or gastric cancer by duration of bisphosphonate therapy.
Nor did cancer rates differ between patients prescribed nitrogen-containing versus non-nitrogen bisphosphonates. (Preclinical studies has yielded evidence suggesting that nitrogen-containing bisphosphonates might reduce cancer risk by affecting tumor proliferation, invasion, and angiogenesis, the authors noted.)
The findings agree with those of prior studies in the U.S. and Denmark. However, both studies identified too few cases of cancer to produce reliable risk estimates (N Engl J Med. 2009;360:1789-1790, N Engl J Med. 2009;360:1791-1792).
Among the limitations of their study, Cardwell and colleagues noted that overestimation of bisphosphonate usage was possible, since patient compliance with bisphosphonate therapy is known to be a problem. Nor was their estimate of cancer incidence derived from a registry, but rather from diagnostic codes in patient files, which may be inaccurate.
They also noted that there was a relatively high proportion of missing data on potential confounders.
Cardwell and coauthors reported that they had no relevant disclosures.
Primary source: Journal of the American Medical Association
Source reference:
Cardwell CR et al. "Exposure to oral bisphosphonates and risk of esophageal cancer" JAMA 2010; 304: 657-663.
  icon paper stack View Older Articles   Back to Top