The use of proton pump inhibitors (PPIs) in patients with a previous hip fracture is associated with increased risk for recurrent hip fracture, except with very low PPI doses, according to study results published in Bone Reports.

There are heterogeneous data regarding the association between the dose and duration of PPI treatment and the risk for hip fracture. Although it is well known that a prior fracture is a major risk factor for subsequent fractures, there are no data regarding the effect of PPI treatment on the risk for recurrent hip fracture.

In this nationwide retrospective study, the researchers aimed to investigate the risk for recurrent hip fracture in adults treated with PPI at different doses. The study enrolled 31,668 Austrian inpatients aged ≥50 years at hospital discharge, who sustained a first hip fracture between July 2008 and December 2010. The participants were followed up until June 2011. For each patient, the cumulative defined daily doses of prescriptions for PPI filled between July 2007 and June 2011 were documented. The primary outcome was 1 or more subsequent hip fracture. Patients were excluded if they were receiving antiosteoporotic medication.

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Use of PPI was associated with an overall elevated risk of sustaining at least 1 subsequent hip fracture (adjusted odds ratio [OR], 1.58; 95% CI, 1.25-2.00; P <.001). The risk was greater in men (adjusted OR, 1.99; 95% CI, 1.19-3.31; P <.01) than in women (adjusted OR, 1.47; 95% CI, 1.13-1.92; P <.01) who received PPIs. The risk was also more pronounced when PPI medication was initiated before the index fracture compared with after the first fracture (adjusted OR, 1.65 vs 1.47, respectively), and the highest risk was evident in PPI users aged 70 to 84 years (adjusted OR, 1.98; 95% CI, 1.32-2.97; P <.001).

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PPI prescription of >90 cumulative defined daily doses was associated with significantly increased risk for recurrent hip fracture. However, prescription of ≤90 cumulative defined daily doses and an average dose of ≤0.25/day were not associated with increased risk for hip fracture compared with the control group.

Overall, the risks for second hip fracture were highest in the first and third year after the index fracture (adjusted OR, 1.75; 95% CI, 1.28-2.38; P <.001; adjusted OR, 1.74; 95% CI, 0.68-4.46; P =.25, respectively), but were only moderately elevated in the second year.

The investigators acknowledged that the study had several limitations, including no data regarding medication other than antiosteoporotic drugs, possible selection bias, and a short study period.

“[G]iven the high prevalence of PPI use among hip fracture patients, the identification of a gender- and age group-related risk profile among PPI users according to when after the index fracture the first subsequent fractures accumulated could have implications for targeted follow-up care for high risk patient groups,” concluded the researchers.

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Brozek W, Reichardt B, Zwerina J, Dimai HP, Klaushofer K, Zwettler E. Higher dose but not low dose proton pump inhibitors are associated with increased risk of subsequent hip fractures after first hip fracture: a nationwide observational cohort study. Bone Rep. 2019;10:100204.