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Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates

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Abstract

Summary

Previous studies have found an association between acid suppressants and fracture risk. We assessed fracture risk in patients taking concomitant acid suppressant and bisphosphonates. Positive associations were observed for any hip and vertebral fracture. The effect size was modest; however, the significance lies in the widespread prescribing of acid suppressants.

Introduction

Previous studies have found that acid-suppressive medication (ASM) is associated with an increased risk of fracture. Bisphosphonates can cause upper gastrointestinal problems, and patients may be prescribed ASM to minimise these effects.

Methods

A retrospective cohort study using the GPRD was conducted in patients aged 40 years and older starting proton pump inhibitors (PPI, N = 234,144), H2 receptor antagonists (H2RA, N = 166,798) or bisphosphonates (N = 67,309). Fracture risk in current versus past use of ASM and concomitant use of bisphosphonate plus ASM versus bisphosphonate alone was compared using time-dependent Cox regression.

Results

In the 6 months before initiating bisphosphonate therapy, 20.1% of patients received a PPI and 7.5% an H2RA. Current PPI use was associated with an increased risk of any (adjusted relative rate (ARR) 1.15, 95% CI 1.10–1.20), hip (ARR 1.22, 95% CI 1.10–1.37), and vertebral fracture (ARR 1.40, 95% CI 1.11–1.78); and concomitant bisphosphonates and PPIs with an increased risk of any (ARR 1.08, 95% CI 1.01–1.16) and hip fracture (ARR 1.24, 95% CI 1.08–1.42).

Conclusions

ASM is associated with an increased risk of fracture when taken alone or in combination with bisphosphonates. Given the frequency of coprescription of ASM and bisphosphonates, this issue requires further investigation.

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Acknowledgements

This study was funded by Servier Laboratories Limited, UK. GPRD is owned by the UK Department of Health and operates within the Medicines and Healthcare products Regulatory Agency (MHRA). GPRD is funded by the MHRA, Medical Research Council, various universities, contract research organisations and pharmaceutical companies. The Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, private–public funded Top Institute Pharma (www.tipharma.nl and includes co-funding from universities, government, and industry), the Dutch Medicines Evaluation Board and the Dutch Ministry of Health. The views expressed in this paper are those of the authors and do not reflect the official policy or position of the Medicines and Healthcare products Regulatory Agency, UK.

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Correspondence to F. de Vries.

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de Vries, F., Cooper, A.L., Cockle, S.M. et al. Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates. Osteoporos Int 20, 1989–1998 (2009). https://doi.org/10.1007/s00198-009-0891-4

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  • DOI: https://doi.org/10.1007/s00198-009-0891-4

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