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Long-term proton pump inhibitor therapy and risk of hip fracture.

Abstract

CONTEXT

Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria but they also may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps.

OBJECTIVE

To determine the association between PPI therapy and risk of hip fracture.

DESIGN, SETTING, AND PATIENTS

A nested case-control study was conducted using the General Practice Research Database (1987-2003), which contains information on patients in the United Kingdom. The study cohort consisted of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years. Cases included all patients with an incident hip fracture. Controls were selected using incidence density sampling, matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date. For comparison purposes, a similar nested case-control analysis for histamine 2 receptor antagonists was performed.

MAIN OUTCOME MEASURE

The risk of hip fractures associated with PPI use.

RESULTS

There were 13,556 hip fracture cases and 135,386 controls. The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59). The risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The strength of the association increased with increasing duration of PPI therapy (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56]; 3 years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001 for all comparisons).

CONCLUSION

Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Division of Gastroenterology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. yangy@mail.med.upenn.edu

    , ,

    Source

    JAMA 296:24 2006 Dec 27 pg 2947-53

    MeSH

    Aged
    Aged, 80 and over
    Anti-Ulcer Agents
    Bone Resorption
    Case-Control Studies
    Enzyme Inhibitors
    Female
    Gastroesophageal Reflux
    Hip Fractures
    Histamine H2 Antagonists
    Humans
    Male
    Middle Aged
    Proton Pump Inhibitors
    Regression Analysis
    Risk

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17190895

    Citation

    Yang, Yu-Xiao, et al. "Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture." JAMA, vol. 296, no. 24, 2006, pp. 2947-53.
    Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-53.
    Yang, Y. X., Lewis, J. D., Epstein, S., & Metz, D. C. (2006). Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA, 296(24), pp. 2947-53.
    Yang YX, et al. Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture. JAMA. 2006 Dec 27;296(24):2947-53. PubMed PMID: 17190895.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Long-term proton pump inhibitor therapy and risk of hip fracture. AU - Yang,Yu-Xiao, AU - Lewis,James D, AU - Epstein,Solomon, AU - Metz,David C, PY - 2006/12/28/pubmed PY - 2007/1/5/medline PY - 2006/12/28/entrez SP - 2947 EP - 53 JF - JAMA JO - JAMA VL - 296 IS - 24 N2 - CONTEXT: Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria but they also may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps. OBJECTIVE: To determine the association between PPI therapy and risk of hip fracture. DESIGN, SETTING, AND PATIENTS: A nested case-control study was conducted using the General Practice Research Database (1987-2003), which contains information on patients in the United Kingdom. The study cohort consisted of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years. Cases included all patients with an incident hip fracture. Controls were selected using incidence density sampling, matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date. For comparison purposes, a similar nested case-control analysis for histamine 2 receptor antagonists was performed. MAIN OUTCOME MEASURE: The risk of hip fractures associated with PPI use. RESULTS: There were 13,556 hip fracture cases and 135,386 controls. The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59). The risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The strength of the association increased with increasing duration of PPI therapy (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56]; 3 years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001 for all comparisons). CONCLUSION: Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/17190895/Long_term_proton_pump_inhibitor_therapy_and_risk_of_hip_fracture_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.296.24.2947 DB - PRIME DP - Unbound Medicine ER -