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Proton Pump Inhibitor Use, H2-Receptor Antagonist Use, and Risk of Incident Clinical Vertebral Fracture in Women

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Abstract

The few prospective studies examining the relation between proton pump inhibitor (PPI) use and risk of vertebral fracture (VF) suggest a higher risk, but the magnitude of the association has been inconsistent. Moreover, no prospective studies have examined the association between substantially longer duration of PPI use and VF risk. Our objective was to determine the association between PPI use, H2RA use, and incident clinical VF in women. We conducted a prospective study in 55,545 women participating in the Nurses’ Health Study. PPI and H2RA use was assessed by questionnaire every 4 years. Self-reports of VF were confirmed by medical record. Our analysis included 547 incident VF cases (2002–2014). The multivariate adjusted relative risk (MVRR) of VF for women taking PPIs was 1.29 (95% CI 1.04–1.59) compared with non-users. Longer duration of PPI use was associated with higher VF risk (MVRR 1.16 [0.90–1.49] for < 4 years; 1.27 [0.93–1.73] for 4–7.9 years; 1.64 [1.02–2.64] for ≥ 8 years; ptrend = 0.01). The MVRR of VF for women taking H2RAs was 1.22 (0.90–1.67) compared with non-users. Longer duration of H2RA use was not associated with VF risk (MVRR 1.16 [0.88–1.53] for < 4 years; 0.98 [0.60–1.59] for ≥ 4 years; ptrend = 0.72). PPI use is independently associated with a modestly higher risk of VF and the risk increases with longer duration of use. There was no statistically significant association between H2RA use and VF risk. Our findings add to the growing evidence suggesting caution with PPI use, particularly with longer duration of use.

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Acknowledgements

We are indebted to the participants in the Nurses’ Health Study for their continuing cooperation.

Funding

This research was supported by the National Institutes of Health grants DK100447, DK091417, and CA186107.

Author information

Authors and Affiliations

  1. Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Julie M. Paik & Gary C. Curhan

  2. Renal Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Julie M. Paik & Gary C. Curhan

  3. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA

    Julie M. Paik & Gary C. Curhan

  4. New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA, USA

    Julie M. Paik

  5. Endocrinology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    Harold N. Rosen

  6. Division of Adolescent and Transition Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Catherine M. Gordon

  7. University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Catherine M. Gordon

  8. Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Room 432, Boston, MA, 02115, USA

    Julie M. Paik

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Contributions

All authors have contributed significantly to the manuscript. Study design: JMP, GCC. Acquisition and analysis of data: JMP. Interpretation of data: All authors. Drafting of the manuscript: JMP, GCC. Critical revision of the manuscript for important intellectual content: All authors. JMP takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Julie M. Paik.

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Conflict of interest

Julie M. Paik, Harold N. Rosen, Catherine M. Gordon and Gary C. Curhan state that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

The study protocol was approved by the Brigham and Women’s Hospital Institutional Review Board.

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Paik, J.M., Rosen, H.N., Gordon, C.M. et al. Proton Pump Inhibitor Use, H2-Receptor Antagonist Use, and Risk of Incident Clinical Vertebral Fracture in Women. Calcif Tissue Int 103, 380–387 (2018). https://doi.org/10.1007/s00223-018-0432-2

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  • DOI: https://doi.org/10.1007/s00223-018-0432-2

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