FRACTURES OSTEOPOROTIQUES Antiépileptiques comme facteur de risque.

Présentation au sujet: "FRACTURES OSTEOPOROTIQUES Antiépileptiques comme facteur de risque."— Transcription de la présentation:

1 FRACTURES OSTEOPOROTIQUES Antiépileptiques comme facteur de risque

2 AE et densité osseuse Méta-analyse (Vestergaard 2005) Méta-analyse (Vestergaard 2005) ( majorité: primidone, phénytoine, carbamazépine, phénobarbital, acide valproïque ):  Diminution de la densité (colonne vert. et femur)

3 Acta Neurol Scand. 2005 Nov;112(5):277-86. Epilepsy, osteoporosis and fracture risk - a meta-analysis. Vestergaard P. Source The Osteoporosis Clinic, Aarhus Amtssygehus, Aarhus University Hospital, Denmark. p-vest@post4.tele.dk Vestergaard P Abstract Abstract This meta-analysis assesses the effects of epilepsy on fracture risk and changes in bone mineral density (BMD) in patients with epilepsy. A search of PubMed was conducted using the key words epilepsy, fracture, and bone mineral. A weighted estimate of relative risk of fractures and changes in BMD (Z-score) was calculated. From the changes in BMD, expected increase in relative fracture risk was calculated. A total of 11 studies on fracture risk and 12 studies on BMD were retrieved. The relative risk of any fracture was increased (2.2, 95% CI: 1.9-2.5, five studies), as was the risk of hip (5.3, 3.2-8.8, six studies), forearm (1.7, 1.2-2.3, six studies), and spine fractures (6.2, 2.5-15.5, three studies). A large proportion of fractures (35%) seemed related to seizures. Spine (mean +/- SEM: -0.38 +/- 0.06) and hip (-0.56 +/- 0.06) BMD Z-scores were significantly decreased, hip more than spine (2P < 0.05). The expected increases in relative risk of any fracture from BMD Z-scores were 1.2-1.3, and significantly lower than observed (2P < 0.05). This meta-analysis assesses the effects of epilepsy on fracture risk and changes in bone mineral density (BMD) in patients with epilepsy. A search of PubMed was conducted using the key words epilepsy, fracture, and bone mineral. A weighted estimate of relative risk of fractures and changes in BMD (Z-score) was calculated. From the changes in BMD, expected increase in relative fracture risk was calculated. A total of 11 studies on fracture risk and 12 studies on BMD were retrieved. The relative risk of any fracture was increased (2.2, 95% CI: 1.9-2.5, five studies), as was the risk of hip (5.3, 3.2-8.8, six studies), forearm (1.7, 1.2-2.3, six studies), and spine fractures (6.2, 2.5-15.5, three studies). A large proportion of fractures (35%) seemed related to seizures. Spine (mean +/- SEM: -0.38 +/- 0.06) and hip (-0.56 +/- 0.06) BMD Z-scores were significantly decreased, hip more than spine (2P < 0.05). The expected increases in relative risk of any fracture from BMD Z-scores were 1.2-1.3, and significantly lower than observed (2P < 0.05). The deficit in BMD in patients with epilepsy is too small to explain the observed increase in fracture risk. The remainder of the increase in fracture risk may be linked to seizures.

4 AE et risque de # Case-controle study( Même méta-analyse): Augmentation: Carbamazépine, oxcarbazépine, clonazépam, phénobarbital, valproïque Tendance d’augmentation: les autres AE (sans significance statistique) (ethosuximide,lamotrigine,phénytoine,primi done,tiagabine,topiramate,vigatrabine)

5 Conclusions: A very limited increased fracture risk is present in users of CBZ, CZP, OXC, PB, and VPA. A limited significant increase cannot be excluded for the other AEDs because of the statistical power. Summary: Purpose: To assess fracture risk associated with different antiepileptic drugs (AEDs). An increased fracture risk has been reported in patients with epilepsy. Classical AEDs have been associated with decreased bone mineral density. The effects of newer AEDs are unknown. Summary: Purpose: To assess fracture risk associated with different antiepileptic drugs (AEDs). An increased fracture risk has been reported in patients with epilepsy. Classical AEDs have been associated with decreased bone mineral density. The effects of newer AEDs are unknown. Methods: We undertook a population-based pharmacoepidemiologic case–control study with any fracture as outcome and use of AEDs as exposure variables (124,655 fracture cases and 373,962 controls). Methods: We undertook a population-based pharmacoepidemiologic case–control study with any fracture as outcome and use of AEDs as exposure variables (124,655 fracture cases and 373,962 controls). Results: All AEDs were associated with an increased fracture risk in an unadjusted analysis. After adjustment for prior fracture, use (ever) of corticosteroids, comorbidity, social variables, and diagnosis of epilepsy, carbamazepine [CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10–1.26], [and oxcarbazepine (OXC; 1.14, 1.03–1.26)], clonazepam (CZP; 1.27, 1.15–1.41), phenobarbital (PB; 1.79, 1.64–1.95), and valproate (VPA; 1.15, 1.05–1.26). Ethosuximide (0.75, 0.37–1.52), lamotrigine (1.04, 0.91–1.19), phenytoin (1.20, 1.00–1.43), primidone (1.18, 0.95–1.48), tiagabine (0.75, 0.40– 1.41), topiramate (1.39, 0.99–1.96), and vigabatrin (0.93, 0.70–1.22) were not statistically significantly associated with fracture risk after adjustment for confounders. The relative increase was modest and in the same range for the significant and nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose–response relation. (1.19; 95% CI, 1.11–1.27). Results: All AEDs were associated with an increased fracture risk in an unadjusted analysis. After adjustment for prior fracture, use (ever) of corticosteroids, comorbidity, social variables, and diagnosis of epilepsy, carbamazepine [CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10–1.26], [and oxcarbazepine (OXC; 1.14, 1.03–1.26)], clonazepam (CZP; 1.27, 1.15–1.41), phenobarbital (PB; 1.79, 1.64–1.95), and valproate (VPA; 1.15, 1.05–1.26) were statistically significantly associated with risk of any fracture. Ethosuximide (0.75, 0.37–1.52), lamotrigine (1.04, 0.91–1.19), phenytoin (1.20, 1.00–1.43), primidone (1.18, 0.95–1.48), tiagabine (0.75, 0.40– 1.41), topiramate (1.39, 0.99–1.96), and vigabatrin (0.93, 0.70–1.22) were not statistically significantly associated with fracture risk after adjustment for confounders. The relative increase was modest and in the same range for the significant and nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose–response relation. Fracture risk was more increased by liver-inducing AEDs (OR, 1.38; 95% CI, 1.31–1.45) than by noninducing AEDs (1.19; 95% CI, 1.11–1.27).

6 Quel AE? en cas d’ostéoporose ou de risque de fracture élevé Ne pas de recommandation Ne pas de recommandation Tous les AE augmentent le risque (somnolence, vertiges, ataxie, risque de fractures, …densité osseuse) Tous les AE augmentent le risque (somnolence, vertiges, ataxie, risque de fractures, …densité osseuse)

7 Ostéodensitométrie? E ou AE ne sont pas des indications en soit pour faire une ostéodensitométrie E ou AE ne sont pas des indications en soit pour faire une ostéodensitométrie Ne sont pas repris dans les critères pour l’ostéodensitométrie Ne sont pas repris dans les critères pour l’ostéodensitométrie(NHG,INAMI,CKS,HAS)

8 Conseils style de vie et alimentaires Le principale source de vit D est l’exposition de la peau au soleil Le principale source de vit D est l’exposition de la peau au soleil Des petites quantités de vitamine D se trouve dans certains aliments, comme: Des petites quantités de vitamine D se trouve dans certains aliments, comme: poisson gras: (soumon, maqeureau, sardines), poisson gras: (soumon, maqeureau, sardines), Jaune d’oeuf, viande, Jaune d’oeuf, viande, certains margarines (ceux qui contiennent 80% de matières grasses) et certains ‘céréales du déjeuner’, soya et produits de régime. certains margarines (ceux qui contiennent 80% de matières grasses) et certains ‘céréales du déjeuner’, soya et produits de régime.

9 Donner Vit D (et Calcium) >>>évaluer les autres facteurs de risque Donner Vit D (et Calcium) si -immobilisation de longue durée -manque d’exposition au soleil -trop peu de Ca alimentaire. Il n’y a pas d’évidence ou consensus concernant le choix de préparation ou concernant le dossage.

10 INAMI\ostéoporose “Les suppléments de calcium et de vitamine D sont à recommander comme mesure générale chez les patients présentant un risque moyen à élevé de fractures, tels que… les patients qui consomment des antiépileptiques,... ”

11 INAMI\ostéoporose Le dosage utilisé Le dosage utilisé 500 à 1 000 mg de calcium élément et 500 à 1 000 mg de calcium élément et 400 à 1 000 UI de vitamine D par jour 400 à 1 000 UI de vitamine D par jour (D-cure 1 ampoule par mois).

12 En cas de manque de vit D démontré (info firme D-cure) 25.000 U.I. (= 1 ampoule/semaine): 25.000 U.I. (= 1 ampoule/semaine): traitement avec des anticonvulsifs (phénobarbital et phénytoïne) avec mise en évidence d'un manque de vitamine D