Dataset Information

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort.

ABSTRACT:

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.

SUBMITTER: Green J

PROVIDER: S-EPMC2933354 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Publications

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort.

Green Jane J Czanner Gabriela G Reeves Gillian G Watson Joanna J Wise Lesley L Beral Valerie V

BMJ (Clinical research ed.) 20100901

<h4>Objective</h4>To examine the hypothesis that risk of oesophageal, but not of gastric or colorectal, cancer is increased in users of oral bisphosphonates.<h4>Design</h4>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.<h4>Setting</h4>UK General Practice Research Database cohort.<h4>Participants</h4>Men and women aged 40 years or over-2954 with oesophageal cancer, 2018 with g ...[more]

PMID: 20813820

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Project description:Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82-1.49; AOR>1-3 years = 1.41; 95% CI:1.01-1.97; AOR>3 years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Project description:Gaps in pharmacological treatment for osteoporosis can reduce effectiveness. Among older adults, we found about half of new users of oral bisphosphonate and denosumab persisted with their treatment at 2 years, with few switching to alternative therapy. Persistence is suboptimal and warrants evaluation of interventions to improve this.PurposeGaps in pharmacological treatment for osteoporosis can reduce effectiveness. This study aimed to estimate persistence rates for oral bisphosphonates and denosumab in older primary care patients and identify factors associated with discontinuation.MethodsOlder patients newly prescribed oral bisphosphonates or denosumab during 2012-2017 were identified from 44 general practices (GP) in Ireland. Persistence without a coverage gap of >90 days was calculated for both medications from therapy initiation. Factors associated with time to discontinuation were explored using Cox regression analysis. Exposures included age group, osteoporosis diagnosis, fracture history, calcium/vitamin D prescription, number of other medications, health cover, dosing frequency (bisphosphonates) and previous bone-health medication (denosumab).ResultsOf 41,901 patients, n=1569 were newly initiated on oral bisphosphonates and n=1615 on denosumab. Two-year persistence was 49.4% for oral bisphosphonates and 53.8% for denosumab and <10% were switched to other medication. Having state-funded health cover was associated with a lower hazard of discontinuation for both oral bisphosphonates (HR=0.49, 95% CI=0.36-0.66, p<0.01) and denosumab (HR=0.71, 95% CI=0.57-0.89, p<0.01). Older age group, number of medications and calcium/vitamin D prescription were also associated with better bisphosphonate persistence, while having osteoporosis diagnosed was associated with better denosumab persistence.ConclusionPersistence for osteoporosis medications is suboptimal. Of concern, few patients are switched to other bone-health treatments when denosumab is stopped which could increase fracture risk. Free access to GP services and medications may have resulted in better medication persistence in this cohort. Future research should explore prescribing choices in primary care osteoporosis management and evaluate cost-effectiveness of interventions for improving persistence.

Dataset Information

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort.

Objective

Design

Setting

Participants

Main outcome measures

Results

Conclusions

Publications

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort.

Similar Datasets

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