title: The effect of VPA on bone: From clinical studies to cell cultures-The molecular mechanisms revisited.
abstract: OBJECTIVE
  Valproic acid (VPA) is a broad-spectrum antiepileptic drug, which is widely used as a first line treatment for idiopathic and symptomatic generalized epilepsy, as well as in non-epileptic psychiatric disorders in adult and pediatric patients. Although valproic acid is considered to be a generally well-tolerated drug, numerous studies have shown an increased bone loss and fracture risk in patients treated with VPA. The purpose of this review is to outline recent findings on VPA molecular mechanisms and their action on bone metabolism.
  
  
  METHODS
  Unrestricted electronic search of medical databases, complemented by additional manual searches, was performed by August 2016.
  
  
  CONCLUSIONS
  The main effects of VPA on bone metabolism involve a decrease in osteoblast proliferation, changes in collagen synthesis as well as an induction of vitamin D catabolism. Apart from these direct actions of VPA in bone, indirect effects affecting other endocrine organs also contribute to VPA-induced bone loss.
authors.affiliation: 1st Neurologic Department, AHEPA University Hospital, Aristotle University of Thessaloniki, AUTH, Greece.
authors.forename: Dimitris A
authors.initials: DA
authors.lastname: Pitetzis
authors.affiliation: 1st Neurologic Department, AHEPA University Hospital, Aristotle University of Thessaloniki, AUTH, Greece.
authors.forename: Martha G
authors.initials: MG
authors.lastname: Spilioti
authors.affiliation: Division of Endocrinology and Metabolism, 1st Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, AUTH, Greece.
authors.forename: John G
authors.initials: JG
authors.lastname: Yovos
authors.affiliation: Division of Endocrinology and Metabolism, 1st Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, AUTH, Greece. Electronic address: margia@med.auth.gr.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Yavropoulou
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001851:Bone Diseases, Metabolic / Q000139:chemically induced; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D014635:Valproic Acid / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D014807:Vitamin D / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D014807:Vitamin D; D014635:Valproic Acid
keywords: Bone metabolism; HDAC; Molecular mechanisms; Valproic acid; Vitamin D