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The Relationship Between Proton Pump Inhibitor Adherence and Fracture Risk in the Elderly

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Abstract

Studies suggest that long-term use of proton pump inhibitors (PPIs) may be associated with an increased risk of fracture. However, the role of medication adherence in this association is not fully understood. A retrospective cohort study was conducted to examine the relationship between PPI use/adherence and fracture risk among elderly subjects by combining administrative pharmacy claims data, survey data, and Medicare data. The study cohort included 1,604 PPI users and 23,672 nonusers who were enrolled in Pennsylvania’s Pharmaceutical Assistance Contract for the Elderly program. PPI adherence was measured by the proportion of days covered (PDC). Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of PPI use/adherence for fracture risk while controlling for demographics, comorbidity, body mass index, smoking, and non-PPI medication use. The overall incidence of any fracture per 100 person-years was 8.7 for PPI users and 5.0 for nonusers. A gradient in fracture risk according to PPI adherence was observed. Relative to nonusers, fracture HRs associated with the highest (PDC ≥ 0.80), intermediate (PDC 0.40–0.79), and lowest (PDC <0.40) adherence levels were 1.46 (p < 0.0001), 1.30 (p = 0.02), and 0.95 (p = 0.75), respectively. In addition, the fracture risk of PPI use was significant for hip (HR = 1.32, p = 0.04) and vertebral (HR = 1.69, p = 0.0005) fractures, and risk was similar between major osteoporotic and other fractures. These results provide further evidence that PPI use may increase fracture risk in the elderly and highlight the need for clinicians to periodically reassess elderly patients’ individualized needs for ongoing PPI therapy, while weighing potential risks and benefits.

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Acknowledgements

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. This report is based on the results of secondary data analysis that was conducted using existing administrative data files. The secondary linkage and use of these data was reviewed and approved by the Institutional Review Board of the Pennsylvania State University.

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Authors and Affiliations

  1. Magellan Health Services/PACE, 4000 Crums Mill Road, Suite 301, Harrisburg, PA, 17112, USA

    Jian Ding & Debra A. Heller

  2. Department of Biobehavioral Health, The Pennsylvania State University, 219 Biobehavioral Health Building, University Park, PA, 16802, USA

    Debra A. Heller & Frank M. Ahern

  3. Pennsylvania Department of Aging, 555 Walnut Street, Forum Place 6th Floor, Harrisburg, PA, 17101, USA

    Theresa V. Brown

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  1. Jian Ding
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Correspondence to Jian Ding.

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Authors Jian Ding, Debra A. Heller, Frank M. Ahern and Theresa V. Brown declare that they have no conflict of interest.

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Ding, J., Heller, D.A., Ahern, F.M. et al. The Relationship Between Proton Pump Inhibitor Adherence and Fracture Risk in the Elderly. Calcif Tissue Int 94, 597–607 (2014). https://doi.org/10.1007/s00223-014-9855-6

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