Association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.
Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide.
Although short term use of PPIs is generally well tolerated, concern has grown over potential association between long term use and bone fractures, especially of the hip, which is known to be associated with substantial morbidity and mortality. PPIs may inhibit calcium absorption, directly interfere with osteoclast function, or induce hypergastrinaemia, resulting in reductions in bone mineral density related to hyperparathyroidism.
· The association between long
term PPI use and risk of hip fracture among postmenopausal women was studied in
a large prospective cohort, the Nurses’ Health Study, where detailed
information about dietary and lifestyle factors are collected biennially.
Main outcome measure Incident hip fracture
Results
· During 565,786 person years
of follow-up, 893 incident hip fractures were documented.
· The absolute risk of hip
fracture among regular users of PPIs was 2.02 events per 1000 person years,
compared with 1.51 events per 1000 person years among non-users.
· Compared with non-users, the
risk of hip fracture among women who regularly used PPIs for at least two years
was 35% higher, with longer use associated with increasing risk (Ptrend<0.01).
· Adjustment for risk factors,
including body mass index, physical activity, and intake of calcium did not
materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These
associations were also not changed after accounting for reasons for PPI use.
· The relation between PPI use
and fracture differed by smoking history (Pinteraction=0.03). Among
current and former smokers, PPI use was associated with greater than 50% increase
in risk of fracture.
· In contrast, among women who never smoked
there was no association.
· In a meta-analysis of these
results with 10 prior studies, the pooled odds ratio of hip fracture associated
with PPI use was 1.30 (1.25 to 1.36).
Among postmenopausal women, regular use of proton pump inhibitors was
associated with a 35% increased risk of hip fracture. The risk seemed to be
confined to women with a history of smoking
