Case-control studycited by the Tayebat archiveabstract only checked★ key study A-PPI-08 in-depth review
PPIs and hip fracture (UK)
Long-term proton pump inhibitor therapy and risk of hip fracture.
Overview
Yang YX et al.. JAMA 2006 · PMID 17190895 · DOI 10.1001/jama.296.24.2947
Use for more than a year was associated with 44% higher odds of hip fracture.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Hip fracture association.
- How was the study done?
Nested case-control in UK GP records.
- How many people, animals or samples were studied?
148,942 people.
- What was actually found?
Higher odds with longer, higher-dose use.
- How large was the observed effect?
AOR 1.44; 2.65.
- What do the results mean in everyday life?
Possible bone risk with long-term use.
- What are the study's limitations?
Confounding by frailty.
- What does it say about Elawady's specific claim?
Partly supports.
- Do the results apply to Germany and Europe?
UK data.
- What can explicitly not be concluded from this study?
Causation.
Scientific in-depth review
1. Full reference
- Authors
- Yang YX, Lewis JD, Epstein S, Metz DC
- Journal
- JAMA
- Year
- 2006
- Identifier
- PMID 17190895 DOI 10.1001/jama.296.24.2947
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract; grants: NIDDK NIH HHS
2. Research question
Association between PPI therapy and hip fracture
3. Study design and population
- Study design
- Case-control study – Nested case-control study, UK General Practice Research Database
- Population
Patients >50 years using PPIs or no acid suppression
- Country
UK
- Period
1987–2003
- Sample size
13,556 cases; 135,386 controls
- Inclusion and exclusion criteria
Incident hip fracture cases; controls by incidence density sampling matched on sex, index date, birth year, follow-up
4. Methods and endpoints
- Exposure / intervention
PPI therapy >1 year; dose; duration
- Comparator
Non-users of acid suppression
- Endpoints
Incident hip fracture
- Statistical methods
Conditional logistic regression (AOR)
5. Actual results
- Results
AOR >1 year PPI 1.44 (1.30–1.59); long-term high dose AOR 2.65 (1.80–3.90); duration gradient 1 yr 1.22, 2 yrs 1.41, 3 yrs 1.54, 4 yrs 1.59.
- Absolute risks
not reported in abstract
- Authors' conclusion
Long-term PPI therapy, particularly at high doses, is associated with increased risk of hip fracture.
6. Strengths
- Large population-based dataset
- Duration and dose gradients
- H2RA comparison analysis
7. Weaknesses
- Observational
- Confounding by frailty, comorbidity and falls risk
- Prescription ≠ intake
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Residual confounding by frailty is the main concern.
9. Assessment of the statistical interpretation
Dose-duration gradient strengthens but does not prove causality.
10. Relevance to the specific claim
11. Independent contrary findings
COMPASS RCT: no significant fracture difference over 3 years.
12. Transferability to Germany and Europe
High: European (Swedish, UK, Dutch, German) data show similar associations; PPIs are widely used in Germany.
13. Overall methodological judgement
Robust association with gradient; causality uncertain.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | high |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | partly correct but over-interpreted |
14. Open questions
Effect after >5 years?
15. Linked fact checks
- Long-term acid suppression causes hip fractures and pneumonia. – Studies supporting the claim
Use by the Tayebat archive
Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.
- What the archive says about the study
UK GPRD nested case-control: PPI use over 1 year raises hip fracture risk 44%; long-term high-dose raises it 2.65-fold.
- A. What was actually studied?
Association of PPI exposure with hip fracture.
- B. What did the authors find?
AOR 1.44 (>1 year), 2.65 (long-term high dose).
- C. What conclusions do the authors themselves draw?
Associated with increased risk.
- D. What does the archive derive from it?
Presented as causal ('raises').
- E. Is this derivation scientifically justified?
Partly: numbers correct; causal wording not justified by case-control design.
- Adequacy of the interpretation (by the archive)
- partly correct but over-interpreted