title: The effect of topiramate and lamotrigine on rat bone mass, structure and metabolism.
abstract: There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models.
authors.affiliation: Department of Neurology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic. 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 in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
authors.forename: Sona
authors.initials: S
authors.lastname: Fekete
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Gradosova
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Malakova
authors.affiliation: Radioisotope Laboratories and Vivarium, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Zivna
authors.affiliation: Department of Neurology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Valis
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Palicka
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Zivny
mesh_terms: D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001696:Biomechanical Phenomena / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077213:Lamotrigine; D008297:Male; D023421:Models, Animal; D009919:Orchiectomy; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D000077236:Topiramate; D014227:Triazines / Q000008:administration & dosage*
chemical_list: D000927:Anticonvulsants; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D053244:Osteoprotegerin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D014227:Triazines; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000077236:Topiramate; D005632:Fructose; D000469:Alkaline Phosphatase; D000077213:Lamotrigine
keywords: Antiepileptic drugs; Bone markers; Bone mineral density; Lamotrigine; Topiramate