2 September 2010 Last updated at 23:03 GMT
Link between bone drugs and oesophageal cancer
Long-term use of bone-strengthening drugs - used to treat fractures - may boost the risk of oesophageal cancer, Oxford University research suggests.
The study of 3,000 people found taking bisphosphonates for five years upped the risk from one in 1,000 to two in 1,000 for 60 to 79-year-olds.
The researchers said the risk was small, but reliable information on risks and benefits was needed.
But experts said for many, the case for taking the drugs "would be strong".
The findings, published in the British Medical Journal, were based on an analysis of anonymised GP records.
They contrast with previous research which found no increased risk for the bone-strengthening drugs.
'Talk to doctor'
It is not known why the risk may be increased, although the drugs are known to irritate the oesophagus.
Thousands of stomach and colorectum cancers were also studied, but no increased risk was found.
Lead researcher Dr Jane Green said even if the findings were confirmed by other studies "few people" taking bisphosphonates would ever develop the cancer.
"Our findings are part of a wider picture. Bisphosphonates are being increasingly prescribed to prevent fracture and what is lacking is reliable information on the benefits and risks of their use in the long term."
About 600,000 people in the UK are currently taking the drugs - including a tenth of all women over the age of 70.
Dr Laura Bell, from Cancer Research UK, agreed the findings should be treated with caution, pointing out the risks were "still small".
"Anyone who is taking these drugs and is worried about their risk of cancer should talk to their doctor."
The National Osteoporosis Society said: "It is a case of balancing the reduced risk of fractures against the side effects of treatment.
"When you consider the fact that there are 230,000 osteoporotic fractures every year in the UK and 1,150 hip-fracture-related deaths every month, the case for treatment is strong."
BMJ 2010; 341:c4444 doi: 10.1136/bmj.c4444 (Published 2 September 2010)
BMJ 2010; 341:c4444
Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort
1. Jane Green, clinical epidemiologist1,
2. Gabriela Czanner, statistician1,
3. Gillian Reeves, statistical epidemiologist1,
4. Joanna Watson, epidemiologist1,
5. Lesley Wise, manager, Pharmacoepidemiology Research and Intelligence Unit2,
6. Valerie Beral, professor of cancer epidemiology1
+ Author Affiliations
1.Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF
2.Medicines and Healthcare products Regulatory Agency, Pharmacoepidemiology Research Unit, London SW8 5NQ
1. Correspondence to: J Green firstname.lastname@example.org
* Accepted 23 June 2010
Objective To examine the hypothesis that risk of oesophageal, but not of gastric or colorectal, cancer is increased in users of oral bisphosphonates.
Design Nested case-control analysis within a primary care cohort of about 6 million people in the UK, with prospectively recorded information on prescribing of bisphosphonates.
Setting UK General Practice Research Database cohort.
Participants Men and women aged 40 years or over―2954 with oesophageal cancer, 2018 with gastric cancer, and 10 641 with colorectal cancer, diagnosed in 1995-2005; five controls per case matched for age, sex, general practice, and observation time.
Main outcome measures Relative risks for incident invasive cancers of the oesophagus, stomach, and colorectum, adjusted for smoking, alcohol, and body mass index.
Results The incidence of oesophageal cancer was increased in people with one or more previous prescriptions for oral bisphosphonates compared with those with no such prescriptions (relative risk 1.30, 95% confidence interval 1.02 to1.66; P=0.02). Risk of oesophageal cancer was significantly higher for 10 or more prescriptions (1.93, 1.37 to 2.70) than for one to nine prescriptions (0.93, 0.66 to 1.31) (P for heterogeneity=0.002), and for use for over 3 years (on average, about 5 years: relative risk v no prescription, 2.24, 1.47 to 3.43). Risk of oesophageal cancer did not differ significantly by bisphosphonate type, and risk in those with 10 or more bisphosphonate prescriptions did not vary by age, sex, smoking, alcohol intake, or body mass index; by diagnosis of osteoporosis, fracture, or upper gastrointestinal disease; or by prescription of acid suppressants, non-steroidal anti-inflammatory drugs, or corticosteroids. Cancers of the stomach and colorectum were not associated with prescription of bisphosphonate: relative risks for one or more versus no prescriptions were 0.87 (0.64 to 1.19) and 0.87 (0.77 to 1.00). The specificity of the association for oesophageal cancer argues against methodological problems in the selection of cases and controls or in the analysis.
Conclusions The risk of oesophageal cancer increased with 10 or more prescriptions for oral bisphosphonates and with prescriptions over about a five year period. In Europe and North America, the incidence of oesophageal cancer at age 60-79 is typically 1 per 1000 population over five years, and this is estimated to increase to about 2 per 1000 with five years’ use of oral bisphosphonates.
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