Fracture risk associated with the use of morphine and opiates


Peter Vestergaard MD, PhD, DrMedSc, Aarhus Amtssygehus, Tage Hansens Gade 2, DK-8000 Aarhus C, Denmark.
(fax: +45 89 49 76 84; e-mail:


Objectives.  To study the effect of morphine and opiates on fracture risk.

Design.  Case–control study.

Setting.  Nationwide register-based study.

Subjects.  Cases were all subjects with any fracture sustained during the year 2000 (n = 124 655). For each case, three controls (n = 373 962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of morphine and opiates. Morphine and other opiates had been used by 10 015 (8.0%) of the case subjects and 12 108 (3.2%) of the controls. Adjustments were made for several confounders including prior fracture, and use of weak analgesics [nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) and acetaminophene]. The effect of dose was examined by stratifying for cumulated dose (defined daily dose).

Main outcome measure.  Fracture.

Results.  Morphine (1.47, 95% CI 1.37–1.58), fentanyl (2.23, 95% CI 1.89–2.64), methadone (1.39, 95% CI 1.05–1.83), oxycodone (1.36, 95% CI 1.08–1.69), nicomorphine (1.57, 95% CI 1.38–1.78), ketobemidone (1.07, 95% CI 1.02–1.13), tramadol (1.54, 95% CI 1.49–1.58) and codeine (1.16, 95% CI 1.12–1.20) were all associated with an increase in overall fracture risk. No increase was present for buprenorphine (0.86, 95% CI 0.79–0.95), pethidine (0.98, 95% CI 0.89–1.08), dextropropoxiphene (1.02, 95% CI 0.90–1.16), and combinations of ASA and codeine (0.94, 95% CI 0.88–1.01).

Conclusions.  An increased fracture risk is seen in users of morphine and opiates. The reason for this may be related to the risk of falls due to central nervous system effects such as dizziness.