Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria.
PPIs may also reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps.
Dr David Metz and colleagues from Philadelphia determined the association between PPI therapy and risk of hip fracture.
The research team conducted a nested case-control study using the General Practice Research Database from 1987 to 2003.
| Hip fracture was increased especially with long-term high-dose PPIs|
|Journal of the American Medical Association|
The database contained 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.
The researchers evaluated all patients with an incident hip fracture.
The team selected controls using incidence density sampling, matched for sex, index date, and year of birth.
In addition, the controls were matched for both calendar period and duration of up-to-standard follow-up before the index date.
For comparison purposes, the researchers performed a similar nested case-control analysis for histamine 2 receptor antagonists.
The team's main outcome measure was the risk of hip fractures associated with PPI use.
The researchers found that there were 13,556 hip fracture cases and 135,386 controls.
The adjusted odds ratio for hip fracture associated with more than 1 year of PPI therapy was 1.4.
The team noted that the risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs.
The strength of the association increased with increasing duration of PPI therapy with an odds ratio of 1.4 at 2, 1.5 at 3 years, and 1.6 at 4 years.
Dr Metz's team concludes, “Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.”