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Bisphosphonates may double cancer risk

Long-term oral bisphosphonates may double risk of oesophageal cancer

Louise Prime

Friday, 03 September 2010

Five years’ use of oral bisphosphonates may double a patient’s risk of developing oesophageal cancer, but not stomach or bowel cancer, UK research published today on bmj.com shows. The findings contradict those of a study we reported last month, published in JAMA, that concluded that oral bisphosphonates did not increase oesophageal cancer risk.

Dr Jane Green and colleagues from the University of Oxford’s Cancer Epidemiology Unit carried out a large-scale study, with the Medicines and Healthcare products Regulatory Agency, to examine further the suspected association between use of oral bisphosphonates for osteoporosis and increased risk of oesophageal cancer.

They analysed data from the UK General Practice Research Database – the same source as that used in August’s JAMA study – on men and women aged over 40 years. They studied 2954 people with oesophageal cancer, 2018 with stomach cancer and 10,641 with colorectal cancer, diagnosed between 1995 and 2005, and compared each case with five controls matched for age, sex, general practice and observation period.

People with at least 10 prescriptions for oral bisphosphonates, or with prescriptions over about five years, had an almost doubled risk of oesophageal cancer compared with people who had not been prescribed the drugs. No association was found for stomach or bowel cancer.

The authors estimate that in absolute terms, the increased risk translates to two cases of oesophageal cancer occurring per 1000 60-79-year-old people taking the drugs over five years, compared with a background risk of one case per 1000.

They point out that although the study published last month in JAMA found no increased risk of oesophageal cancer with bisphosphonate use, their own bmj.com research “had the potential to include people with longer durations of bisphosphonate use and also had greater statistical power, with five matched controls per case compared with equal numbers in the exposed and comparison groups in Cardwell et al’s study.”

Lead author Jane Green says: “Oesophageal cancer is uncommon. The increased risks we found were in people who used oral bisphosphonates for about five years, and even if our results are confirmed, few people taking bisphosphonates are likely to develop oesophageal cancer as a result of taking these drugs.

“Our findings are part of a wider picture. Bisphosphonates are being increasingly prescribed to prevent fractures, and what is lacking is reliable information on the benefits and risks of their use in the long term.”

Dr Diane Wysowski, an epidemiologist at the US Food and Drug Administration, discusses the differences between the JAMA and bmj.com studies in her accompanying editorial. She says: “The possibility of adverse effects on the oesophagus should prompt doctors who prescribe these drugs to consider risks versus benefits” and suggests that they “tell patients to report difficulty in swallowing and throat, chest, or digestive discomfort so that they can be promptly evaluated and possibly advised to discontinue the drug.” 

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