Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study.
BACKGROUND
Patients using higher dosages of inhaled or oral glucocorticoids (GCs) have an increased risk of hip/femur fractures. The role of the underlying disease in the aetiology of this increased risk has not been widely studied.


OBJECTIVE
To evaluate the contribution of the underlying disease to the risk of hip/femur fracture in patients using inhaled or oral GCs.


METHODS
A case-control study within the Dutch PHARMO-RLS database was conducted. Cases (n = 6763) were adult patients with a first hip/femur fracture during enrolment. Each case was matched to four controls by age, gender and region.


RESULTS
The risk of hip/femur fracture increased with current use of inhaled GCs (crude OR 1.30, 95% CI:1.16-1.47) and with current use of oral GCs (crude OR 1.66, 95% CI: 1.46-1.90). After adjustment for disease severity, the risk of hip/femur fracture was no longer statistically significantly increased in inhaled GC users (adjusted OR 1.08, 95% CI: 0.91-1.27), whilst it remained elevated in oral GC users (adjusted OR 1.43, 95% CI: 1.22-1.67). Patients using inhaled GCs without any exposure to oral GCs had no increased risk of fracture (adjusted OR 0.98, 95% CI: 0.79-1.22).


CONCLUSIONS
Inhaled GC users had no increased risk of femur/hip fracture after adjustment for underlying disease severity. Our data suggest that, even at higher dosages, inhaled GC use is not an independent risk factor for fracture. In contrast, oral GC use was associated with an increased risk of fracture, which was not fully explained by the underlying disease severity.
de Vries
F
F
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Pouwels
S
S
Lammers
J W J
JW
Leufkens
H G M
HG
Bracke
M
M
Cooper
C
C
van Staa
T P
TP
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016208:Databases, Factual; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006620:Hip Fractures / Q000139:chemically induced*; D006801:Humans; D007154:Immune System Diseases / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009426:Netherlands
D005938:Glucocorticoids