Proton Pump Inhibitors May Increase Risk for Hip Fractures

Proton pump inhibitors (PPIs) are associated with an increased risk for hip fractures after more than five years of continuous use, according to the results of a new study.

Researchers from the University of Manitoba (Winnipeg, Canada) conducted a retrospective, matched-cohort study using a population health research data repository for Manitoba (Canada). Case patients were defined as those 50 years or older who had seen a clinician or been admitted with vertebral, hip, or wrist fracture between April 1996 and March 2004. Each one of the 15,792 case patients was matched with three control subjects--a total of 47,289 subjects--on the basis of age, sex, and comorbidity conditions. Adjusted odds ratios (ORs) were calculated for the risk for hip fracture and all osteoporosis-related fractures for PPI use ranging from one or more years to more than seven years.

The results showed that the risk for all hip fractures increased after five or more years of exposure to PPIs, and the risk was even higher after seven or more years of exposure. Moreover, although the use of PPIs for durations of six years or less was not significantly associated with the overall risk for an osteoporosis-related fracture, the risk for such a fracture was significantly increased with exposure to PPIs for seven or more years. Limitations of the study included lack of anthropomorphic data and information regarding the use of over-the-counter calcium supplements, vitamin D supplements, tobacco, and alcohol; inability to determine whether increased fracture risk from PPIs is related to reduced bone density or increased risk for falls; observational design; and inability to identify fractures that did not lead to a clinician interaction. The researcher recommended that PPIs be used only if clinically indicated and suggested that anti-osteoporosis therapy may be considered with long-term use of PPIs. The study was published in the August 2008, issue of the Canadian Medical Association Journal (CMAJ).

"Use of proton pump inhibitors for seven or more years is associated with a significantly increased risk of an osteoporosis-related fracture,” concluded lead author Laura Targownik, M.D., MSHS, and colleagues of the department of gastroenterology. "There is an increased risk of hip fracture after five or more years of exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.”

Proton pump inhibitors are benzimidazole derivatives and are the most potent inhibitors of gastric acid secretion currently available; they act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system of the gastric parietal cell. PPIs have largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H2-receptor antagonists.

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