title: Monotherapy with Levetiracetam Versus Older AEDs: A Randomized Comparative Trial of Effects on Bone Health.
abstract: Long-term anti-epileptic drug (AED) therapy is associated with increased fracture risk. This study tested whether substituting the newer AED levetiracetam has less adverse effects on bone than older AEDs. An open-label randomized comparative trial. Participants had "failed" initial monotherapy for partial epilepsy and were randomized to substitution monotherapy with levetiracetam or an older AED (carbamazepine or valproate sodium). Bone health assessments, performed at 3 and 15 months, included areal bone mineral density (aBMD) and content at lumbar spine (LS), total hip (TH), forearm (FA), and femoral neck (FN), radial and tibial peripheral quantitative computed tomography and serum bone turnover markers. Main outcomes were changes by treatment group in aBMD at LS, TH, and FA, radial and tibial trabecular BMD and cortical thickness. 70/84 patients completed assessments (40 in levetiracetam- and 30 in older AED group). Within-group analyses showed decreases in both groups in LS (-9.0 %; p < 0.001 in levetiracetam vs. -9.8 %; p < 0.001 in older AED group), FA (-1.46 %; p < 0.001 vs. -0.96 %; p < 0.001, respectively) and radial trabecular BMD (-1.46 %; p = 0.048 and -2.31 %; p = 0.013, respectively). C-terminal telopeptides of type I collagen (βCTX; bone resorption marker) decreased in both groups (-16.1 %; p = 0.021 vs. -15.2 %; p = 0.028, respectively) whereas procollagen Ι N-terminal peptide (PΙNP; bone formation marker) decreased in older AED group (-27.3 %; p = 0.008). The treatment groups did not differ in any of these measures. In conclusion, use of both levetiracetam and older AEDs was associated with bone loss over 1 year at clinically relevant fracture sites and a reduction in bone turnover.
authors: Department of Neurology, The Royal Melbourne Hospital, Melbourne, Australia.|Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building Royal Parade, The Royal Melbourne Hospital, Parkville, 3050, VIC, Australia.|Faculty of Medicine, Jazan University, Jazan, Saudi Arabia.
authors: Tahir
authors: T
authors: Hakami
authors: Department of Neurology, The Royal Melbourne Hospital, Melbourne, Australia.|Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building Royal Parade, The Royal Melbourne Hospital, Parkville, 3050, VIC, Australia.
authors: Terence J
authors: TJ
authors: O'Brien
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building Royal Parade, The Royal Melbourne Hospital, Parkville, 3050, VIC, Australia.
authors: Sandra J
authors: SJ
authors: Petty
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building Royal Parade, The Royal Melbourne Hospital, Parkville, 3050, VIC, Australia.
authors: Mary
authors: M
authors: Sakellarides
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building Royal Parade, The Royal Melbourne Hospital, Parkville, 3050, VIC, Australia.
authors: Jemma
authors: J
authors: Christie
authors: Bone Densitometry Unit, The Royal Melbourne Hospital, Melbourne, Australia.
authors: Susan
authors: S
authors: Kantor
authors: Department of Neurology, The Royal Melbourne Hospital, Melbourne, Australia.|Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building Royal Parade, The Royal Melbourne Hospital, Parkville, 3050, VIC, Australia.
authors: Marian
authors: M
authors: Todaro
authors: The Melbourne EpiCentre, The Royal Melbourne Hospital, Melbourne, Australia.
authors: Alexandra
authors: A
authors: Gorelik
authors: Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia.
authors: Markus J
authors: MJ
authors: Seibel
authors: Department of Neurology, The Royal Melbourne Hospital, Melbourne, Australia.
authors: Raju
authors: R
authors: Yerra
authors: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building Royal Parade, The Royal Melbourne Hospital, Parkville, 3050, VIC, Australia. jdwark@unimelb.edu.au.|Bone & Mineral Medicine, The Royal Melbourne Hospital, Melbourne, Australia. jdwark@unimelb.edu.au.
authors: John D
authors: JD
authors: Wark
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D002220:Carbamazepine / Q000009:adverse effects; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives*; D014057:Tomography, X-Ray Computed; D014635:Valproic Acid / Q000009:adverse effects
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D000077287:Levetiracetam; D014635:Valproic Acid; D010889:Piracetam
keywords: Antiepileptic drugs; Bone health; Epilepsy