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Common Osteoporosis Drug Linked To Higher Risk Of Esophageal Cancer

A new UK study that followed a large number of people found that those who took 10 or more prescriptions for oral bisphosphonates, a group of drugs commonly used to treat the bone disease osteoporosis, were at higher risk of developing esophageal cancer.

You can read about the research behind this finding in a paper published online in the British Medical Journal, BMJ on 2 September. The study was led by a team from the Cancer Epidemiology Unit at the University of Oxford, and the lead and corresponding author of the paper is Dr. Jane Green, a clinical epidemiologist at the Unit.

In Europe and North America, the risk of developing esophageal cancer is very small, typically about 1 per 1,000 people aged 60 to 79 over five years.

Green and colleagues estimated that taking 10 or more prescriptions for oral bisphosphonates and taking them over a period of five years doubles that risk.

However, the authors themselves and experts commenting in an accompanying editorial said this evidence is not enough to justify doctors changing their prescription policy, but they should perhaps prescribe more cautiously and be more vigilant about follow up.

In many countries, including the UK and the US, oral bisphosphonates are the recommended first line drugs for preventing bone fracture in people with osteoporosis, a common disease that affects especially postmenopausal women.

In their paper, the authors note that prescribing of bisphosphonates is increasing; for example in the UK, the percentage of women aged over 70 receiving prescriptions for oral bisphosphonates has gone up from 3 per cent in 2000 to 10 per cent in 2005.

For their study they searched the UK General Practice Research Database cohort for cases where men and women aged 40 and over, with esophageal (2,954 cases), gastric (2,018), and colorectal (10,641) cancer, diagnosed between 1995 and 2005, and their prescription medication were being followed.

To estimate the relative risk of incident invasive cancer of the esophagus, stomach, or colorectum, they matched the cancer cases with controls (5 controls per case) of the same age, sex, attending the same general practice, and who were followed for the same period.

After adjusting the results for known risk factors such as smoking, alcohol and body mass index, the researchers found that:

  • The rate of esophageal cancer was increased in patients with one or more previous prescriptions for oral bisphosphonates compared with those who had no prescriptions (relative risk RR was 1.30, 95% confidence interval CI ranged from 1.02 to1.66; statistical significance P=0.02).
  • However, this risk was significantly higher in those patients whose records showed they had 10 or more prescriptions (RR 1.93, CI 1.37 to 2.70), compared to those who had 9 or less (RR 0.93, CC 0.66 to 1.31; P for heterogeneity=0.002).
  • This was also the case for patients whose records showed they took the drugs for over 3 years: eg. for an average of about 5 years, the RR for prescription vs no prescription was 2.24, with CI 1.47 to 3.43.
  • esophageal cancer risk did not differ significantly by bisphosphonate type, and for patients taking 10 or more prescriptions, it did not vary by age, gender, smoking status, alcohol consumption, or body mass index.
  • And neither did it vary by diagnosis of osteoporosis, fracture, or upper gastrointestinal disease, nor by whether the patients were also prescribed acid suppressants, non-steroidal anti-inflammatory drugs, or corticosteroids.
  • Stomach and colorectal cancers were not associated with being prescribed with bisphosphonates.

The authors concluded that:

“The risk of esophageal cancer increased with 10 or more prescriptions for oral bisphosphonates and with prescriptions over about a five year period.”

They explained that this approximately doubles the small risk of developing esophageal cancer, which in Europe and North America is about 1 per 1,000 people aged 60-79.

They wrote that treatment of osteoporosis is a growing public health concern, “with large scale clinical and economic implications”, and that if confirmed, these findings “would add to our knowledge of the risks and benefits of use of oral bisphosphonates”.

However, they stressed that further studies are needed to “confirm or refute” these findings, and particularly to “examine the associations between use of different types and formulations of bisphosphonates and risk of the different histological types of esophageal cancer”.

Green and colleagues also mention a JAMA study published last month conducted by Cardwell et. al., that also used the UK General Practice Research Database but found no link between oral bisphosphonates and risk of esophageal cancer.

However, they suggest the reason this study has found a link and the JAMA one did not, was the difference in the observation time: Cardwell et. al. analyzed data covering an average of 4.5 years whereas Green et. al. covered 7.7 years on average:

“Our study thus 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,” they write.


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