title: The effect of lamotrigine and phenytoin on bone turnover and bone strength: A prospective study in Wistar rats.
abstract: Some data suggest that exposure to lamotrigine (LTG) might be associated with impaired bone health in an orchidectomized rat model. The aim of this study was to determine if LTG poses any significant risk for bone in a gonadally intact animals and to compare the effect of LTG with that of phenytoin (PHT).
  
  
  
  Twenty-four rats were divided into control and test groups, (n=8 per group). Control rats received a standard laboratory diet (SDL), while rats in the test groups were fed a SLD enriched with LTG or PHT for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). The concentrations of bone turnover markers (BTM) were assayed in bone homogenates. The femurs were measured and biomechanically tested.
  
  
  
  Treatment with either LTG or PHT had no significant effect on BMD or on the biomechanical strength of the bones. In contrast to the effect of LTG, we did find significant changes in BTM in the PHT group: a highly significant decrease in the osteoprotegerin/receptor activator of nuclear factor kappa B ratio (p<0.01) and highly significant increases in bone alkaline phosphatase and amino-terminal propeptide of procollagen type I (p<0.001, p˂0.01, respectively). In the LTG group, the only significant change was a decrease in sclerostin (p˂0.05). The PHT level was 19.0 (15.6-19.5) μmol/l, which represents the lower end of the therapeutic range used in humans. The level of LTG was 60.7 (58.5-61.8) μmol/l.
  
  
  
  LTG has no effect on the BMD, BTM or mechanical strength in gonadally intact animals. Although a low dose of PHT was associated with enhanced BTM, it did not affect BMD or the biomechanical properties of the bones, similar to the results observed for LTG.
authors.affiliation: Department of Neurology, Charles University, Faculty of Medicine and University Hospital, Hradec Kralove, Czechia. Electronic address: simko.julius@gmail.com.
authors.forename: Julius
authors.initials: J
authors.lastname: Simko
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Czechia.
authors.forename: Iva
authors.initials: I
authors.lastname: Karesova
authors.affiliation: Department of Pathophysiology, Charles University, Faculty of Medicine in Hradec Kralove, Czechia.
authors.forename: Jan
authors.initials: J
authors.lastname: Kremlacek
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Czechia.
authors.forename: Sona
authors.initials: S
authors.lastname: Fekete
authors.affiliation: Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University, Czechia.
authors.forename: Eva
authors.initials: E
authors.lastname: Zimcikova
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Czechia.
authors.forename: Jana
authors.initials: J
authors.lastname: Malakova
authors.affiliation: Radioisotope Laboratories and Vivarium, Charles University, Faculty of Medicine in Hradec Kralove, Czechia.
authors.forename: Helena
authors.initials: H
authors.lastname: Zivna
authors.affiliation: Department of Neurology, Charles University, Faculty of Medicine and University Hospital, Hradec Kralove, Czechia.
authors.forename: Martin
authors.initials: M
authors.lastname: Valis
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine and University Hospital in Hradec Kralove, Czechia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Palicka
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D000077213:Lamotrigine; D008137:Longitudinal Studies; D008297:Male; D010672:Phenytoin / Q000494:pharmacology*; D011446:Prospective Studies; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D015415:Biomarkers; D014227:Triazines; D010672:Phenytoin; D000077213:Lamotrigine
keywords: Amino-terminal propeptide of procollagen type I; Bone alkaline phosphatase; Bone mineral density; Bone turnover markers; Osteoprotegerin/receptor activator of nuclear factor kappa B ratio; Sclerostin