Researchers Take Another Look at Bisphosphonate-Cancer Link
Earlier this month, researchers from the United Kingdom released their findings from a large study involving bisphosphonate use (drugs that treat osteoporosis) and its association with esophagitis and esophageal cancer link. At the time, the researchers admitted that there was a lack of investigative evidence to conclusively state that drugs such as Fosamax, Actonel, and Boniva increased the risk of esophageal cancer. But now the group is taking a second look at the data.
Oral Bisphosphonate Use is Linked to Adverse Esophageal Changes
In an analysis of about 80,000 patients included in the UK General Practice Research database, Dr. Jane Green of the University of Oxford and colleagues evaluated the data collected for more than seven years and found that individuals who were diagnosed with esophageal cancer were 1.93 times as likely to have received at least 10 prescriptions for oral bisphosphonates compared with those controls without cancer.
About 3.1 percent of the esophageal cancer patients had received at least one prescription before diagnosis, compared with 2.4 percent of the controls. The relationship appeared to strengthen with the number of prescriptions and the estimated duration of use.
"Our study ... had the potential to include people with longer durations of bisphosphonate use and also had greater statistical power," Dr. Green asserted. But the researchers do not ultimately conclude that oral bisphosphonate use contributes to cancer but they note that they could not “rule out the possibility”.
In an accompanying editorial, Diane Wysowski, an epidemiologist with the US Food and Drug Administration, says that the agency has collected a total of 68 case reports of esophageal cancer in patients taking the osteoporosis drugs. While esophagitis (inflammation of the esophagus), erosion, and stricture are known adverse effects, no label warnings – called a “black box warning” - have yet been ordered for oral bisphosphonates.
Overall, says Wysowski, the incidence in the population is expected to be relatively low, but doctors should consider the possibility of risk when prescribing oral bisphosphonates for osteoporosis treatment. Physicians should also reiterate the importance of following the strict instructions for taking the drugs, which minimize the drug’s direct contact with the esophageal tract.
For Fosamax, the instructions read:
• You must take alendronate just after you get out of bed in the morning, before you eat or drink anything. Never take alendronate at bedtime or before you wake up and get out of bed for the day.
• Swallow alendronate tablets with a full glass (6 to 8 ounces [180 to 240 milliliters]) of plain water. Drink at least a quarter of a cup (2 ounces [60 milliliters]) of plain water after you take alendronate solution. Never take alendronate tablets or solution with tea, coffee, juice, milk, mineral water, sparkling water, or any liquid other than plain water.
• Swallow the tablets whole; do not split, chew or crush them. Do not suck on the tablets.
• After you take alendronate, do not eat, drink, or take any other medications (including vitamins or antacids) for at least 30 minutes. Do not lie down for at least 30 minutes after you take alendronate. Sit upright or stand upright until at least 30 minutes have passed and you have eaten your first food of the day.
Patients who have difficulty swallowing or other gastrointestinal symptoms should promptly contact their physician.
"Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort."
Jane Green, Gabriela Czanner, Gillian Reeves, Joanna Watson, Lesley Wise, and Valerie Beral. BMJ 2010; 341:c4444
Published online 2 September 2010 DOI: 10.1136/bmj.c4444