Background/Purpose: Proton pump inhibitors (PPI), which are often recommended in patients with rheumatic diseases due to frequent use of high risk medications such as NSAIDs or high dose steroids, have been associated with an increased risk for fractures. However, it is unknown whether associated chronic comorbidities contribute to the fracture risk observed from PPI use.

Methods: Using a unique medical records linkage system available in our community to undertake population-based studies, we identified 3433 community residents age ≥ 50 yrs (2269 [66%] women; 1164 men; mean age 70 yrs) who had any fracture during a 3-year period (2009-2011) and an equal number of age- and sex- matched controls from the same population who had no fractures in this time period. All fractures were validated and their antecedent cause determined by trained nurse abstractors through review of complete (inpatient and outpatient) community medical records. Using our unique resources enabling access to all medical records in the community, we identified PPI use as well as the Elixhauser Comorbidity Index (ECI) and its components in the 5 yrs prior to fracture/index date for both cases and controls. To determine whether the use of PPIs was higher among fracture cases than non-fracture controls after accounting for comorbidity differences, propensity score methodology was used to estimate inverse probability weights (IPW). The IPW were used with a weighted logistic regression model, further adjusted for age and ECI, to examine the association between PPI use (of at least 2 yrs) and fracture risk.

Results: PPI use was more common among fracture cases than non-fracture controls (35% vs 27%). Comorbidities were not only more common among fracture cases than controls (45% vs 33%, with at least 5 Elixhauser comorbidities), they were also more frequent among those who had used a PPI compared with those who had not (63% vs 34% in fracture cases, 51% vs 26% in controls). While the association between PPI use and increased fracture risk was attenuated in adjusted analyses, when compared with unadjusted analyses, it remained persistent but modestly elevated (unadjusted vs adjusted odds ratios (OR), respectively: OR: 1.50 [95% CI: 1.33-1.69] vs 1.18 [95% CI: 1.02-1.37] for any fracture; OR: 1.72 [95% CI: 1.44-2.05] vs 1.25 [95% CI: 1.01-1.55] for any major osteoporotic site [hip, spine, wrist, shoulder] fracture). We found similar results when considering only moderate trauma fractures (i.e. fractures due to a fall from a standing height or less) or any PPI use (data not shown). Using similar methods, we found no association between H2-blocker use and fracture risk (data not shown).

Conclusion: While we found an association between PPI use and increased fractures, this risk was more modest after accounting for associated chronic comorbidities, which is relevant when weighing the risks vs benefits of continuing PPI use.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/attenuated-association-between-proton-pump-inhibitor-use-and-fracture-risk-after-consideration-of-chronic-comorbidities/