title: Long-Term Proton Pump Inhibitor Use Is Not Associated With Changes in Bone Strength and Structure.
abstract: 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.
authors.affiliation: Section of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.|Manitoba Inflammatory Bowel Disease Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Targownik
authors.affiliation: Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada.|Section of Nuclear Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Goertzen
authors.affiliation: Department of Mechanical Engineering, University of Manitoba, Winnipeg, Manitoba, Canada.|Graduate Program in Biomedical Engineering, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada.|Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Leslie
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000378:metabolism; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015331:Cohort Studies; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging* / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D016014:Linear Models; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008350:Manitoba / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005755:Gastrins; D010281:Parathyroid Hormone; D010455:Peptides; D010710:Phosphates; D054328:Proton Pump Inhibitors; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase; D008274:Magnesium; D002118:Calcium