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Is allopurinol use associated with an excess risk of osteoporotic fracture? A National Prescription Registry study

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Abstract

Summary

Using a Danish Register cohort of 86,039 adult new allopurinol users and propensity score matched controls, we found that gout requiring allopurinol prescription was associated with an increased fracture risk.

Purpose

Gout, an acute inflammatory arthritis, is common and associated with elevated serum urate, obesity and high alcohol consumption. The mainstay of therapy is the urate-lowering agent, allopurinol. Here, we report the relationship between allopurinol prescription and fracture in a large registry population.

Methods

We established a Danish Register cohort of 86,039 adult cases (new allopurinol users) and 86,039 age, sex and propensity score matched controls (not exposed to allopurinol or with a gout diagnosis), with no diagnosis of malignancy in the year prior.

Results

We found a modest adjusted effect of allopurinol prescription on major osteoporotic fractures (hazard ratio (HR) 1.09, 95 % confidence interval (CI) 1.05–1.14, p = 0.04) and on hip fractures (HR 1.07, 95 % CI 1.11–1.14, p < 0.001), robust to adjustment for confounding factors (age, sex, comorbidity, medication use). Associations were stronger in men than women, and among incident allopurinol users whose gout diagnosis had been confirmed by at least one hospital contact. Prespecified subanalyses by filled dose of allopurinol (mg/day in first year of prescription) showed increased hip and major fracture risk in women in the highest allopurinol dose grouping only, while a less strong dose effect was evident for fracture rates in men.

Conclusion

Gouty arthritis requiring allopurinol is associated with an excess risk of major or hip fracture, with an allopurinol dose effect evident in women such that women taking the highest doses of allopurinol—suggestive of more severe disease—were at increased risk relative to women taking lower doses.

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Conflict of interest

Elaine Dennison, Katrine Hass Rubin, Peter Schwarz, Nicholas Harvey, Karen Walker Bone, Cyrus Cooper and Bo Abrahamsen declare that they have no conflict of interest to declare in relation to this manuscript. ED has received speaker fees from Lilly; NH has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare and Internis Pharma. CC has received consultancy fees/honoraria from Servier, Eli Lilly, Merck, Amgen, Novartis and Medtronic. BA has received consultancy fees/honoraria from Nycomed, Takeda, Merck, Amgen, Novartis/ Eli Lilly.

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Authors and Affiliations

  1. MRC Lifecourse Epidemiology Units, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

    Elaine M. Dennison, Nicholas C. Harvey, Karen Walker Bone & Cyrus Cooper

  2. Victoria University of Wellington, Wellington, New Zealand

    Elaine M. Dennison

  3. Odense Patient data Explorative Network (OPEN), Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

    Katrine Hass Rubin & Bo Abrahamsen

  4. Department of Medicine, Holbæk Hospital, Holbæk, Denmark

    Peter Schwarz & Bo Abrahamsen

  5. NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton, Southampton, UK

    Elaine M. Dennison, Nicholas C. Harvey & Cyrus Cooper

  6. NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK

    Cyrus Cooper

Authors
  1. Elaine M. Dennison
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  2. Katrine Hass Rubin
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  3. Peter Schwarz
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  4. Nicholas C. Harvey
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  5. Karen Walker Bone
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  6. Cyrus Cooper
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  7. Bo Abrahamsen
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Corresponding author

Correspondence to Elaine M. Dennison.

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Dennison, E.M., Rubin, K.H., Schwarz, P. et al. Is allopurinol use associated with an excess risk of osteoporotic fracture? A National Prescription Registry study. Arch Osteoporos 10, 36 (2015). https://doi.org/10.1007/s11657-015-0241-4

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  • DOI: https://doi.org/10.1007/s11657-015-0241-4

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