Opioid use for noncancer pain and risk of fracture in adults: a nested case-control study using the general practice research database

Am J Epidemiol. 2013 Aug 15;178(4):559-69. doi: 10.1093/aje/kwt013. Epub 2013 May 2.


Opioid use has been reported to be associated with increased fracture risks. In a nested case-control study using the United Kingdom-based General Practice Research Database, we tested the hypotheses that fracture risk was associated with 1) an elevated risk of falls caused by the acute central nervous system effects of opioids including sedation and dizziness, and 2) osteoporosis caused by chronic opioid-induced hypogonadism. Among a cohort of adults aged 18-80 years without cancer who received ≥1 opioid prescription during 1990-2008, we selected cases with a first diagnosed fracture of the hip, humerus, or wrist; up to 4 controls, matched by age, sex, index date (date of the first diagnosed fracture), and general practice, were randomly selected for each case. Adjusted odds ratios and 95% confidence intervals were estimated by using conditional logistic regression. Current use of 1 prescription was associated with a strong risk of fracture (adjusted odds ratio = 2.70, 95% confidence interval: 2.34, 3.13). The risk decreased with increasing use. There was no association with current use of >20 opioid prescriptions. The findings were consistent for all study fractures and for most common opioids, suggesting that acute central nervous system effects of opioids rather than chronic opioid-induced hypogonadism play a key role in fracture risk.

Keywords: General Practice Research Database; fracture; nested case-control study; noncancer pain; opioids.

MeSH terms

  • Accidental Falls*
  • Aged
  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / therapeutic use
  • Case-Control Studies
  • Central Nervous System / drug effects*
  • Comorbidity
  • Conscious Sedation / adverse effects
  • Dizziness / chemically induced
  • Female
  • Fractures, Bone / epidemiology
  • Fractures, Bone / etiology*
  • General Practice / statistics & numerical data
  • Humans
  • Hypogonadism / chemically induced*
  • Hypogonadism / complications
  • Logistic Models
  • Male
  • Osteoporosis / complications
  • Osteoporosis / etiology*
  • Pain / drug therapy*
  • Risk Factors
  • United Kingdom / epidemiology


  • Analgesics, Opioid