Fracture risk associated with the use of morphine and opiates.
OBJECTIVE
To study the effect of morphine and opiates on fracture risk.


METHODS
Case-control study.


METHODS
Nationwide register-based study.


METHODS
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).


METHODS
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.
Vestergaard
P
P
Department of Endocrinology and Metabolism, Aarhus Sygehus, Aarhus University Hospital, Aarhus, Denmark. p-vest@post4.tele.dk
Rejnmark
L
L
Mosekilde
L
L
D000058:Accidental Falls / Q000706:statistics & numerical data; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects*; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects*; D010024:Osteoporosis / Q000150:complications / Q000453:epidemiology; D018570:Risk Assessment
D000701:Analgesics, Opioid; D009020:Morphine