Long-term proton pump inhibitor therapy and risk of hip fracture.
BACKGROUND
Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria but they also may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps.


OBJECTIVE
To determine the association between PPI therapy and risk of hip fracture.


METHODS
A nested case-control study was conducted using the General Practice Research Database (1987-2003), which contains information on patients in the United Kingdom. The study cohort consisted of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years. Cases included all patients with an incident hip fracture. Controls were selected using incidence density sampling, matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date. For comparison purposes, a similar nested case-control analysis for histamine 2 receptor antagonists was performed.


METHODS
The risk of hip fractures associated with PPI use.


RESULTS
There were 13,556 hip fracture cases and 135,386 controls. The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59). The risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The strength of the association increased with increasing duration of PPI therapy (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56]; 3 years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001 for all comparisons).


CONCLUSIONS
Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.
Yang
Yu-Xiao
YX
Division of Gastroenterology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. yangy@mail.med.upenn.edu
Lewis
James D
JD
Epstein
Solomon
S
Metz
David C
DC
D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001862:Bone Resorption; D016022:Case-Control Studies; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006620:Hip Fractures / Q000453:epidemiology*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors; D012044:Regression Analysis; D012306:Risk
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors