Proton Pump Inhibitors and Risk of Fracture: A Systematic Review and Meta-Analysis of Observational Studies
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
OBJECTIVES: Proton pump inhibitors (PPIs) are widely used in several acid-related gastrointestinal disorders. In vivo studies have suggested that gastric suppression by PPIs could result in decreased intestinal calcium absorption. Subsequently, there have been concerns that the chronic use of a PPI is associated with an increased risk of bone fracture. However, the results of clinical studies are conflicting. METHODS: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risks of PPI use on fracture outcome. All controlled observational studies that compared fracture outcome in patients with PPI therapy with a control group were included. We calculated pooled odds ratios (ORs) using a random-effects model. RESULTS: Of 1,668 identified studies, 10 (4 cohort and 6 case-control) with 223,210 fracture cases were included in our analysis. In PPI users, compared with non/past users, the OR for hip fracture (n=9) was 1.25 (95% confidence interval (CI)=1.14-1.37). The OR for vertebral fracture (n=4) was 1.50 (95% CI=1.32-1.72) and for wrist/forearm fracture (n=3) was 1.09 (95% CI=0.95-1.24). In subgroup analysis of hip fracture, this association was observed in both high-dose and low-dose PPI exposure. When stratified by duration of exposure, the short duration of PPI use was associated with increased risk of developing hip fracture (OR=1.24; 95% CI=1.19-1.28), whereas there was no significant increase in risk of hip fracture in long-term PPI users (OR=1.30; 95% CI=0.98-1.70). There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the subgroup analyses. CONCLUSIONS: Our results should be interpreted with caution. We found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding. Thus, randomized controlled studies are required to confirm or refute these results.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.014 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it