Gastroenterology

Gastroenterology

Volume 138, Issue 3, March 2010, Pages 896-904
Gastroenterology

Clinical—Alimentary Tract
Proton-Pump Inhibitor Use Is Not Associated With Osteoporosis or Accelerated Bone Mineral Density Loss

https://doi.org/10.1053/j.gastro.2009.11.014Get rights and content

Backgrounds & Aims

Recent studies have shown an association between proton-pump inhibitor use (PPI) and hip fracture. The mechanism by which PPI use promotes the development of hip fracture is uncharacterized. Therefore, we sought to determine whether PPI use is associated with osteoporosis or accelerated bone mineral density (BMD) loss.

Methods

We used the Manitoba Bone Mineral Density Database to determine the relationship between chronic PPI use and osteoporosis on an initial assessment of BMD and on BMD loss between successive assessments of BMD. In the cross-sectional study, cases with osteoporosis at the hip or lumbar vertebrae (T-score ≤−2.5) were matched to 3 controls with normal BMD (T-score ≥−1.0). In the longitudinal analysis, the change in BMD among PPI users and nonusers between successive BMD assessments was assessed. Conditional logistic regression and multivariate linear regression were used to obtain estimates of the association between PPI use and osteoporosis and of the annualized change in BMD associated with PPI use.

Results

PPI use was not associated with having osteoporosis at either the hip (OR, 0.84; 95% CI, 0.55–1.34) or the lumbar spine (OR, 0.79; 95% CI, 0.59–1.06) for PPI use >1500 doses over the previous 5 years. In the longitudinal study no significant decrease was observed in BMD at either site attributable to PPI use.

Conclusions

PPI use does not appear to be associated with either the presence of osteoporosis or accelerated BMD loss. The association between PPI use and hip fracture is probably related to factors independent of osteoporosis.

Section snippets

Materials and Methods

Two separate analyses were performed. In the cross-sectional study, we compared subjects with established osteoporosis, as determined by BMD testing, to controls with normal BMD. In the longitudinal study, we analyzed the change in BMD on serial assessments between PPI users and non-PPI users. The methodology used in each of these studies is described below in detail.

Results

In the cross-sectional study, 2193 subjects had evidence of osteoporosis at the hip and were matched to 5527 controls with normal hip measurements. A total of 3596 subjects had BMD measurements consistent with osteoporosis at the lumbar spine and were in turn matched to 10,257 normal controls. A description of patient demographics, BMI, medical comorbidities, and medication use is shown in Table 1.

In univariate analyses, PPI use was associated with a lower risk of osteoporosis at the lumbar

Discussion

Our results indicate that a history of chronic PPI use is not associated with an increased likelihood of having BMD in the osteoporotic range at either the hip or the lumbar spine. Furthermore, increasing intensity of PPI exposure is not associated with an increased risk of having osteoporosis. The lack of an association between PPI use and changes in BMD was further confirmed in the longitudinal assessment. An effect of PPIs on the rate of bone mineral loss was also not detected among subjects

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    Conflicts of interest The authors disclose the following: Dr Laura Targownik has served on advisory boards for Janssen-Ortho Canada and Astra-Zeneca Canada and on the speaker's bureau for Astra-Zeneca Canada. Both companies either currently or at one time marketed particular proton pump inhibitors in Canada. The remaining authors disclose no conflicts.

    Funding Dr Targownik is supported by a Canadian Institutes of Health Research New Investigator Grant in Osteoporosis, and by Osteoporosis Canada. Dr Leslie is supported by the Canadian Institutes of Health Research. Dr Lix is supported by a CIHR New Investigator Award. This project was funded by a grant from the Canadian Institutes of Health Research Regional Partnership Program and the Manitoba Health Research Council.

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