Multiple studies have reported an association between proton pump inhibitor (PPI) use and fracture. However, the causality of this association is questionable, as there is not a well defined mechanism of action, nor is there evidence of an effect on PPIs on areal bone mineral density (aBMD) using dual photon X-ray absorptiometry (DXA). It is possible that PPIs may induce changes in bone structure which would predispose to fracture in the absence of changes in aBMD. We used three-dimensional quantitative computed tomography (3D-QCT) imaging to determine if long-term PPI use was associated with structural changes in bone independent of aBMD.
We enrolled a sample of long-term (≥5 years) PPI users matched to a similar cohort of persons with no PPI use in the previous 5 years. All subjects underwent assessment of aBMD using DXA, volumetric BMD using 3D-QCT, as well as markers of bone metabolism. Measures of bone strength, including buckling ratio and section modulus, were also compared between the two samples.
104 subjects were enrolled (52 PPI users and 52 PPI non-users). There were no differences detected in standard BMD, volumetric BMD, markers of bone metabolism or measures of bone strength between the two groups.
Long-term PPI use is not associated with any changes in bone mineral density or bone strength that would predispose to an increased risk of fracture. These findings provide further evidence that the association between PPI use and fracture is not causal.
1Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
2Manitoba Inflammatory Bowel Disease Research Centre, Winnipeg, Manitoba, Canada
3Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada
4Section of Nuclear Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada
5Department of Mechanical Engineering, University of Manitoba, Winnipeg, Manitoba, Canada
6Graduate Program in Biomedical Engineering, University of Manitoba, Winnipeg, Manitoba, Canada
7Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Correspondence: Laura E. Targownik, MD, MSHS, Department of Internal Medicine, University of Manitoba, Manitoba Inflammatory Bowel Disease Research Centre, 805G-715 McDermot Avenue, Winnipeg, Manitoba, R3E 3P4, Canada. E-mail: laura.targownik@med.umanitoba.ca
Guarantor of the article: Laura Targownik, MD, MSHS.
Specific author contributions: All Authors were responsible for: planning and conducting the study, collecting and interpreting data, and drafting the manuscript. For each author, there should also be a statement. All authors have approved the final version of this manuscript.
Financial support: This research was supported by a Canadian Institutes of Health Research Priority Award in Osteoporosis.
Potential competing interests: Laura Targownik: Received Investigator Initiated Grant Support from Abbvie Canada, Janssen Canada and Pfizer Canada. Attended Advisory Boards for Takeda Canada, Janssen Canada, and Pfizer Canada, Speakers’ Panels for Takeda Canada, Janssen Canada. William Leslie: Has served as a speaker for Amgen, Eli Lily, and Novartis, and has received research grants from Amgen. Yunhua Luo, Andrew Goertzen: none.
