On July 21, 2011 the FDA issued a safety announcement concerning their ongoing investigation of oral osteoporosis drugs (bisphosphonates) and the potential increased risk of esophageal cancer.
The statement states, “[t]here have been conflicting findings from studies evaluating this risk. Therefore at this time, FDA believes that the benefits of oral bisphosphonate drugs in reducing the risk of serious fractures in people with osteoporosis continue to outweigh their potential risks.”
In January 2009, a case series was published describing reports submitted to the FDA of esophageal cancer in patients prescribed oral bisphosphonates.Since then, several epidemiological studies looking at the association between oral bisphosphonates and esophageal cancer have been published, with discrepant findings.
The two largest published studies used data from the U.K.’s General Practice Research Database (GPRD). One study compared the rate of esophageal cancer in patients taking an oral bisphosphonate to patients not taking an oral bisphosphonate. This study found no increase in the risk of esophageal cancer.
Using the same database, a second study found a doubling of the risk of esophageal cancer among patients who had 10 or more prescriptions of oral bisphosphonates, or who had taken the drugs over 3 years.
Other investigators are researching this issue. In a large cohort of Danish patients with fractures, investigators found that bisphosphonate users (who had taken them for a median of 1.5 years) had a significantly reduced risk for esophageal cancer compared to patients with fractures who had not taken any bisphosphonate.
Longer term follow-up of alendronate (Fosamax) users and non-alendronate users showed that alendronate users had a higher frequency of endoscopic examination of the esophagus, no greater incidence of esophageal cancer, and no increase in esophageal cancer deaths.
Differences in methodologies in these studies may account for the discrepant findings. Also, since these studies are observational rather than randomized, they are subject to bias and confounding. For example, it is possible that the gastrointestinal side effects of bisphosphonates increase a patient’s likelihood of undergoing an endoscopy, which could lead to earlier detection of a cancer or drug discontinuation.
Oral bisphosphonates are commonly used for the prevention and treatment of osteoporosis as well as to treat other bone diseases such as Paget’s disease. Osteoporosis is a disease that makes bones weak and more likely to break. Common oral bisphosphonates include: Fosamax (alendronate), Actonel (risedronate), Boniva (ibandronate), Atelvia (risedronate delayed release), Didronel (etidronate), and Skelid (tiludronate).
They may cause irritation of the esophagus. Irritation of the esophagus can lead to esophagitis (inflammation) or esophageal ulcers (sores), which may bleed. The risk of these esophageal events is low when oral bisphosphonates are prescribed appropriately and the specific directions for use are followed by patients.
FDA has advised medical professionals that there are insufficient data to recommend endoscopic screening of asymptomatic patients. That esophagitis and other esophageal events have been reported, particularly in patients who do not follow the specific directions for use of oral bisphosphonates. So, it is imperative that they instruct patients to carefully follow the directions for use of the oral bisphosphonate drug they are prescribed.
Patients should talk with their healthcare professionals about the benefits and risks of taking oral bisphosphonates. Patients who take oral bisphosphonates should pay particular attention to the directions for use to minimize any potential adverse events.
FDA will continue to evaluate all available data supporting the safety and effectiveness of bisphosphonate drugs and will update the public when more information becomes available.