Fracture Risk Appears Higher With PPIs Than With H2RAs

Proton-pump inhibitors (PPIs) appear to carry a higher risk of bone fractures than histamine-2 receptor antagonists (H2RAs), according to two new studies, one in South Korean women and one in kidney-transplant recipients in the US.

PPIs are more potent gastric-acid suppressors than H2RAs, and this has boosted their use globally, Dr. Yun-Mi Song of Sungkyunkwan University School of Medicine, in Seoul, and colleagues note in Bone. However, they add, "Recent studies have suggested that long-term PPI use might be associated with an increased risk of osteoporotic fracture by reducing calcium and vitamin B12 absorption, possibly via the potent inhibition of gastric acid secretion."

The team conducted a nationwide nested case-control study in women who underwent measurements of bone-mineral density at age 66 during a so-called "life-transition medical examination" between 2009 and 2014.

They identified more than 8,900 women diagnosed with new osteoporotic fractures and five times as many matched controls. After adjustment for covariates, any PPI use was associated with a significantly increased risk of fractures compared with H2RA use only (adjusted odds ratio, 1.13), and the risk tended to increase with greater duration of PPI use.

PPI use within the past year was associated with a significantly increased risk of fracture (aOR, 1.31), but earlier PPI use was not. There was, however, no trend in the fracture risk associated with an increase in cumulative PPI dose.

Their study is the "first of its kind to demonstrate the longitudinal associations of the risk of fracture associated with PPI use compared with H2RA use in a large, general population using a well-established and validated longitudinal national database," Dr. Song's team writes.

They conclude: "The risk of osteoporotic fracture may be mitigated in women with gastrointestinal diseases who need acid inhibitor treatments and are at a high risk of osteoporotic fracture by prescribing PPI for minimal durations or replacing PPI with H2RA."

In the second study, researchers at the University of Wisconsin-Madison used the Wisconsin Allograft Recipient Database to identify 155 kidney-transplant recipients with a major fracture occurring at least 12 months after transplantation. They matched the cases to 685 controls.

PPI use, but not H2RA use, in the past year was significantly associated with higher fracture risk even in a fully adjusted model (aOR, 1.7), Dr. Brad Astor and colleagues report in Transplantation.

Kidney-transplant recipients face about a four times higher risk of fracture than the general population, particularly in the first 1 to 3 years after kidney transplantation, the team notes.

"Our results suggested PPI use might be one of the modifiable risk factors for fracture in KTRs," they write. "In addition, H2RA could be an alternative to PPI for prophylaxis of gastrointestinal complications after transplantation given their overall lack of association with fracture risk."

Neither of the authors could be reached for comments.

—Scott Baltic

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