Fracture risk with intermittent high-dose oral glucocorticoid therapy

Authors

  • Frank De Vries,

    1. University of Utrecht, Utrecht, The Netherlands
    Search for more papers by this author
  • Madelon Bracke,

    1. University of Utrecht, and Utrecht Medical Center, Utrecht, The Netherlands
    Search for more papers by this author
  • Hubert G. M. Leufkens,

    1. University of Utrecht, Utrecht, The Netherlands
    Search for more papers by this author
  • Jan-Willem J. Lammers,

    1. Utrecht Medical Center, Utrecht, The Netherlands
    Search for more papers by this author
  • Cyrus Cooper,

    1. Southampton General Hospital, and University of Southampton, Southampton, UK
    Search for more papers by this author
    • Dr. Cooper has received consulting fees and/or honoraria (less than $10,000 each) from Servier, Procter & Gamble, Eli Lilly, and GlaxoSmithKline/Roche. Dr. van Staa was previously employed by Procter & Gamble Pharmaceuticals and acquired stock in Procter & Gamble during his period of employment.

  • Tjeerd P. Van Staa

    Corresponding author
    1. University of Utrecht, Utrecht, The Netherlands, Southampton General Hospital and University of Southampton, Southampton, UK, and the Medicines and Healthcare Products Regulatory Agency, London, UK
    • Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
    Search for more papers by this author
    • Dr. Cooper has received consulting fees and/or honoraria (less than $10,000 each) from Servier, Procter & Gamble, Eli Lilly, and GlaxoSmithKline/Roche. Dr. van Staa was previously employed by Procter & Gamble Pharmaceuticals and acquired stock in Procter & Gamble during his period of employment.


Abstract

Objective

To evaluate the risk of fracture in patients receiving intermittent therapy with high-dose oral glucocorticoids (GCs).

Methods

The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of “current” and “no exposure.” The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation.

Results

Patients who intermittently received high-dose GCs (daily dose ≥15 mg) and had no or little previous exposure to GCs (cumulative exposure ≤1 gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this risk increased substantially with increasing cumulative exposure. Among patients who received a daily dose ≥30 mg and whose cumulative exposure was >5 gm, the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval [95% CI] 2.54–5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49–6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29–25.08).

Conclusion

Intermittent use of high-dose oral GCs (daily dose ≥15 mg and cumulative exposure ≤1 gm) may result in a small increased risk of osteoporotic fracture. Conversely, patients who receive several courses of high-dose GCs (daily dose ≥15 mg and cumulative exposure >1 gm) have a substantially increased risk of fracture.

Ancillary