title: Early detection of bone metabolism changes under different antiepileptic drugs (ED-BoM-AED)--a prospective multicenter study.
abstract: OBJECTIVE
  To determine early changes in bone turnover markers induced by treatment with oxcarbazepine or valproate.
  
  
  METHODS
  In this prospective study, 31 adults with newly diagnosed epilepsy were included who were started on therapy with either oxcarbazepine (OXC, n=16, mean age 45.6 years, 37.5% female) or valproate (VPA, n=15, mean age 42.2 years, 33.3% female). Clinical characteristics were obtained at baseline, after 2 weeks and 3 months. In addition, blood samples were drawn at each visit. Calcium, phosphate, alkaline phosphatase (AP), receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC) and cathepsin K were determined.
  
  
  RESULTS
  In OXC treated patients, OPG increased by 0.06 pmol/L (p=0.0004) after 2 weeks and remained elevated by 0.05 pmol/L (p=0.02) after 3 months. Between 2 weeks and 3 months of OXC treatment, OC increased by 1.98 ng/mL (p=0.02). During the first 3 months of OXC treatment, total serum AP increased by 11%±9% (p=0.02). Compared to baseline, serum calcium raised by 0.06 mmol/L (p=0.04) after 2 weeks and by 0.07 mmol/L (p=0.004) after 3 months of OXC treatment. In VPA treated patients, a late OPG increase by 0.07 pmol/L (p=0.007) occurred after 3 months. During the first 3 months of OXC treatment, total serum AP decreased by by 7%±15% (p=0.03). No changes in OC or calcium were seen. RANKL was below detection limit in 16 out of 31 patients (52%) and did not change significantly during treatment. Cathepsin K was below detection limit at baseline in 27 out of 31 patients (87%) and was therefore not further evaluated. Phosphate did not change during treatment.
  
  
  CONCLUSIONS
  Increased bone turnover can be measured within few weeks of newly started treatment with OXC, while significant changes under VPA treatment occurred only after 3 months. Our data suggest distinct mechanisms of increased bone turnover in different anticonvulsants. These variable mechanisms may require individual prevention and treatment strategies.
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Germany. Electronic address: bauerse@med.uni-marburg.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.forename: Adam
authors.initials: A
authors.lastname: Strzelczyk
authors.forename: Christoph
authors.initials: C
authors.lastname: Kellinghaus
authors.forename: Susanne
authors.initials: S
authors.lastname: Hallmeyer-Elgner
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Felix
authors.initials: F
authors.lastname: Rosenow
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D000078330:Oxcarbazepine; D010710:Phosphates / Q000378:metabolism; D011446:Prospective Studies; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D053244:Osteoprotegerin; D010710:Phosphates; D053246:Receptor Activator of Nuclear Factor-kappa B; D015675:Osteocalcin; D002220:Carbamazepine; D014635:Valproic Acid; D002118:Calcium; D000078330:Oxcarbazepine
keywords: Bone turnover; Osteoprotegerin; Oxcarbazepine; RANKL; Valproate