Article date: November 2010
Oral bisphosphonates are used to treat osteoporosis, Paget’s disease, and bone-related cancers. There is clear evidence that nitrogen-containing bisphosphonates (ie, alendronic acid, ibandronic acid, and risedronate) can cause oesophageal irritation and reactions. After reports of oesophageal cancer in association with oral bisphosphonates, we collaborated with the Cancer Epidemiology Unit at the University of Oxford to conduct a study to assess this issue.
The results from this study suggest a small increase in the risk of oesophageal cancer in patients who had taken oral bisphosphonates for more than 5 years compared with a group who had not taken oral bisphosphonates. The incidence rate of oesophageal cancer over 5 years in men and women aged 60–79 years in the general population is 0.5 women per 1000 and 1.5 men per 1000. In this study, the incidence increased with 5 years’ of bisphosphonates use to one woman per 1000, and three men per 1000. By contrast, other studies have not reported a link.
These studies were considered as part of a Europe-wide review of oral bisphosphonates and oesophageal cancer. This review concluded that given the limitations of the study by Green and colleagues1 and a lack of supporting evidence from other studies, there is insufficient evidence to confirm a link between oral bisphosphonate use and oesophageal cancer. The limitations of the study included little available information for risk factors for oesophageal cancer (such as smoking, alcohol consumption, social deprivation, and previous oesophageal reactions). Furthermore, patients receiving oral bisphosphonates are more likely to be monitored for oesophageal reactions than those not receiving bisphosphonates, which may result in an increased detection of oesophageal cancer in patients receiving bisphosphonates.
Information and advice for healthcare professionals and patients to minimise risk of oesophageal adverse reactions with oral bisphosphonates:
- alendronate and oral ibandronate should not be given to patients with abnormalities of the oesophagus and/or other factors which delay oesophageal emptying such as stricture or achalasia. Risedronate should be used with caution in such patients
- alendronate, oral ibandronate, and risedronate should be used with caution in patients with active or recent upper gastrointestinal problems
- in patients with known Barrett’s oesophagus, prescribers should consider the benefits and potential risks of alendronate and oral ibandronate on an individual basis
Advice for patients:
- patients should be advised about the importance of adhering to dose instructions
- tablets should be swallowed whole with at least 200 mL water on an empty stomach immediately after getting up in the morning
- patients should stay fully upright for at least 30 minutes or 1 hour after taking the tablet and before taking any food, drink, or other medicine as outlined in the product information
- patients should be advised to stop taking the tablets and to seek medical attention if they develop any symptoms of oesophageal irritation such as difficulty or pain on swallowing, chest pain, or new or worsening heartburn
Bisphosphonate product information
Questions and answers on the study by Green and colleagues
See also report from the European Pharmacovigilance Working Party, October 2010
Article citation: Drug Safety Update Nov 2010 vol 4, issue 4: H1.
Published 11 December 2014