How Valproate Affects Bones

A proteomic study suggests how the epilepsy and bipolar disorder drug sodium valproate leads to bone loss: It reduces production of collagen and osteonectin, both critical proteins for bones (J. Proteome Res., DOI: 10.1021/pr1005263). Valproate has been in use for more than 40 years, mostly as an anticonvulsant or mood stabilizer. But the reason for its bone loss side effect has not been clear. The drug, which inhibits the enzyme histone deacetylase, has been suggested as a possible treatment for spinal muscular atrophy, a degenerative inherited neuromuscular disease. Glenn E. Morris and colleagues at Robert Jones & Agnes Hunt Orthopedic & District Hospital, in Oswestry, England, found bone loss clues in a study of possible valproate side effects in skin cells from spinal muscular atrophy patients. Valproate significantly reduced levels of osteonectin and several different subtypes of collagen, leaving more than 1,000 other proteins unchanged. The researchers believe valproate might exacerbate any bone weakness already present in spinal muscular atrophy patients. They are currently investigating valproate’s effect on bone cells to better characterize the drug’s mechanism of action.