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Excess risk of hip fractures attributable to the use of antidepressants in five European countries and the USA

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Abstract

Summary

The association between antidepressant use and hip fracture remains unclear. We conducted a systematic review to estimate Population Attributable Risks (PAR) for France, Germany, Italy, Spain, UK, and the USA. We report a heterogeneous prevalence of antidepressant use and related PARs, both lowest for Italy and highest for the USA.

Introduction

Antidepressant use has been associated with an increased hip fracture risk in observational studies. However, the potential contribution of antidepressant consumption on the population rate of hip fractures has not been described. Our aim was to estimate the impact of the use of different classes of antidepressants on the rate of hip fracture at a population-level in France, Germany, Italy, Spain, the UK, and the USA.

Methods

We conducted a systematic literature review to estimate the pooled relative risk (RR) of hip fracture according to use of antidepressants. Prevalence rates of antidepressant use (Pe) in 2009 were calculated for each country using the The Intercontinental Medical Statistics database and three public databases from Denmark, the Netherlands, and Norway. Both the RR and Pe were used to calculate PAR of hip fractures associated with antidepressant use.

Results

The literature review showed an increased risk of hip fractures in antidepressant users (RR, 1.7; 95 % confidence interval (CI), 1.5–2.0). Rates of antidepressant use showed considerable differences between countries, ranging from 4.4 % (Italy) to 11.2 % (USA) in the year 2009. The estimated PAR of antidepressants on hip fracture rates were 3.0 % (95 % CI, 2.0–4.1; Italy), 3.1 % (95 % CI, 2.1–4.3; Germany), 3.8 % (95 % CI, 2.6–5.3; France), 4.8 % (95 % CI, 3.3–6.5; Spain), 4.9 % (95 % CI, 3.4–6.8; UK), and 7.2 % (95 % CI, 5.0–9.9; USA). PARs differed for different types of antidepressants, with highest attributable risks for selective serotonin reuptake inhibitors.

Conclusions

These findings suggest that the potential contribution of antidepressant use to the population rate of hip fractures in the five large EU countries and the USA varies between 3 and 7 %.

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Conflicts of interest

OK has received unrestricted funding for pharmacoepidemiological research from the private-public funded Top Institute Pharma (www.tipharma.nl). DPA has received partial support from unrestricted research grants by AMGEN SA and BIOIBERICA S.A. The authors PK, JG, NJR, and HP were all employees of Roche at the time of conduct of this research. Roche does not produce antidepressant drugs, which are the subject of this publication. JG is currently an employee of Abbott Healthcare Products B.V. in the Netherlands. She conducted this work as part of an internship at Roche when she was a student at Utrecht University.

The research leading to these results was conducted as part of the PROTECT consortium (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium; www.imi-protect.eu) which is a public-private partnership coordinated by the European Medicines Agency.

The PROTECT project has received support from the Innovative Medicine Initiative Joint Undertaking (www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.

In the context of the IMI Joint Undertaking (IMI JU), the Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, also received a direct financial contribution from Pfizer. The views expressed are those of the authors only and not of their respective institution or company.

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Authors and Affiliations

  1. Oxford National Institute for Health and Research (NIHR) Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK

    D. Prieto-Alhambra

  2. Medical Research Council (MRC) Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK

    D. Prieto-Alhambra

  3. Epidemiology and Patient Reported Outcomes, Roche Products Limited, Shire Park, 6 Falcon Way, Welwyn Garden City, AL7 1TW, UK

    H. Petri, J. S. B. Goldenberg & T. P. Khong

  4. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Utrecht, The Netherlands

    J. S. B. Goldenberg, T. P. Khong, O. H. Klungel & F. de Vries

  5. Abbott Healthcare Products B.V., Weesp, The Netherlands

    J. S. B. Goldenberg

  6. Epidemiology and Patient Reported Outcomes, Hoffman-La Roche, Building 663, Grenzacherstrasse 124, 4070, Basel, Switzerland

    N. J. Robinson

  7. Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, Maastricht, Netherlands

    F. de Vries

  8. CAPHRI School for Public Health and Primary Care, Maastricht, The Netherlands

    F. de Vries

  9. GREMPAL Research Group, IDIAP Jordi Gol, Primary Care Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain

    D. Prieto-Alhambra

  10. Musculoskeletal Research Group, IMIM-Parc de Salut Mar, Barcelona, Spain

    D. Prieto-Alhambra

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  1. D. Prieto-Alhambra
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Correspondence to F. de Vries.

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Prieto-Alhambra, D., Petri, H., Goldenberg, J.S.B. et al. Excess risk of hip fractures attributable to the use of antidepressants in five European countries and the USA. Osteoporos Int 25, 847–855 (2014). https://doi.org/10.1007/s00198-013-2612-2

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