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Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy.
Neurology. 2006 May 09; 66(9):1318-24.Neur

Abstract

OBJECTIVE

To study the association between use of antiepileptic drugs (AEDs) and risk of fractures.

METHODS

The authors obtained data from the General Practice Research Database (GPRD). A case-control study was nested within a cohort of patients with active epilepsy. Cases were patients with a first fracture after cohort entry. Up to four controls were matched to each case by practice, sex, year of birth, timing of first epilepsy diagnosis, index date, and duration of GPRD history. Cumulative exposure to AEDs was assessed by summing the duration of all AED prescriptions. A distinction was made between AEDs that induce the hepatic cytochrome P-450 enzyme system and AEDs that do not. Medical conditions and drugs known to be associated with bone metabolism or falls were evaluated as potential confounders. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs.

RESULTS

The study population comprised 1,018 cases and 1,842 matched controls. The risk of fractures increased with cumulative duration of exposure (p for trend < 0.001), with the strongest association for greater than 12 years of use: adjusted OR 4.15 (95% CI 2.71 to 6.34). Risk estimates were higher in women than in men. There was no difference between users of AEDs that induce and AEDs that do not induce the hepatic cytochrome P-450 system.

CONCLUSIONS

Long-term use of AEDs was associated with an increased risk of fractures, especially in women. More research on mechanisms of AED-induced bone breakdown and female vulnerability to the effects of AEDs on bone health is warranted.

Authors+Show Affiliations

Department of Pharmacoepidemiology and Pharmacotherapy, Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. p.c.souverein@pharm.uu.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16682661

Citation

Souverein, P C., et al. "Use of Antiepileptic Drugs and Risk of Fractures: Case-control Study Among Patients With Epilepsy." Neurology, vol. 66, no. 9, 2006, pp. 1318-24.
Souverein PC, Webb DJ, Weil JG, et al. Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy. Neurology. 2006;66(9):1318-24.
Souverein, P. C., Webb, D. J., Weil, J. G., Van Staa, T. P., & Egberts, A. C. (2006). Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy. Neurology, 66(9), 1318-24.
Souverein PC, et al. Use of Antiepileptic Drugs and Risk of Fractures: Case-control Study Among Patients With Epilepsy. Neurology. 2006 May 9;66(9):1318-24. PubMed PMID: 16682661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy. AU - Souverein,P C, AU - Webb,D J, AU - Weil,J G, AU - Van Staa,T P, AU - Egberts,A C G, PY - 2006/5/10/pubmed PY - 2006/6/13/medline PY - 2006/5/10/entrez SP - 1318 EP - 24 JF - Neurology JO - Neurology VL - 66 IS - 9 N2 - OBJECTIVE: To study the association between use of antiepileptic drugs (AEDs) and risk of fractures. METHODS: The authors obtained data from the General Practice Research Database (GPRD). A case-control study was nested within a cohort of patients with active epilepsy. Cases were patients with a first fracture after cohort entry. Up to four controls were matched to each case by practice, sex, year of birth, timing of first epilepsy diagnosis, index date, and duration of GPRD history. Cumulative exposure to AEDs was assessed by summing the duration of all AED prescriptions. A distinction was made between AEDs that induce the hepatic cytochrome P-450 enzyme system and AEDs that do not. Medical conditions and drugs known to be associated with bone metabolism or falls were evaluated as potential confounders. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs. RESULTS: The study population comprised 1,018 cases and 1,842 matched controls. The risk of fractures increased with cumulative duration of exposure (p for trend < 0.001), with the strongest association for greater than 12 years of use: adjusted OR 4.15 (95% CI 2.71 to 6.34). Risk estimates were higher in women than in men. There was no difference between users of AEDs that induce and AEDs that do not induce the hepatic cytochrome P-450 system. CONCLUSIONS: Long-term use of AEDs was associated with an increased risk of fractures, especially in women. More research on mechanisms of AED-induced bone breakdown and female vulnerability to the effects of AEDs on bone health is warranted. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/16682661/Use_of_antiepileptic_drugs_and_risk_of_fractures:_case_control_study_among_patients_with_epilepsy_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=16682661 DB - PRIME DP - Unbound Medicine ER -