Fracture Risk Associated with Enzyme-Inducing Antiepileptic Drugs in Patients with Epilepsy: A Systematic Review (P4.274)
Bibliographic record
Abstract
OBJECTIVE: To determine whether patients with epilepsy (PWE) treated with enzyme-inducing anti-epileptic drugs (EIAED) have either decreased bone mineral density (BMD) or increased fracture incidence versus those treated with non-EIAED. BACKGROUND: PWE have increased fracture risk, independent of seizures. Certain antiepileptic drugs (AED) are believed to increase this risk, particularly AEDs that induce the liver p450 enzyme system. DESIGN/METHODS: We searched MedLine, EMBase, CENTRAL, and CINAHL prior to November 2013 for all studies/abstracts comparing fracture risk or BMD change in PWE treated for 蠅 1 year with EIAED versus non-EIAED. No age, gender, publication date, or language restrictions were applied. RESULTS: Of the 1,770 articles identified, 13 observational studies met eligibility criteria and were included in the review: 7 cross-sectional, 4 cohort, 1 case-control, and 1 nested case-control study. These studies, representing 68,611 adult PWE, were significantly heterogeneous, making meta-analysis impossible. Study results were split, with 5 studies showing decreased BMD in EIAED users, 5 studies showing no effect of EIAED on BMD, 2 studies showing increased fracture incidence in EIAED users, and 1 study showing no difference in fracture risk. The largest study (n=63,259), which dominated the review and was the most methodologically rigorous of all included studies, showed an increased relative risk of 9-22[percnt] for any fracture, and 49-53[percnt] for hip fracture, in EIAED users. CONCLUSIONS: The literature is divided regarding the bone effects of EIAED; however, because the largest and highest-quality study to-date shows increased fracture risk associated with EIAED, current best evidence supports an increased fracture risk in PWE treated with EIAED compared to those treated with non-EIAED. Other large, methodologically rigorous, studies are needed to confirm/refute the results of this single dominant paper. Further small studies, with limited power to control for multiple potentially confounding variables, are not likely to help. Study Supported by: N/A
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.022 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.009 |
| Bibliometrics | 0.008 | 0.012 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".