Valproate, a drug commonly used to treat epilepsy, bipolar disorder, and spinal muscular atrophy (SMA), can cause bone depletion, says a new study.

Valproate reduces the formation of two key proteins considered important for bone strength, thereby decreasing the production of collagen by 60 cent and levels of osteonectin by 28 percent in patients with SMA, says the study conducted at the RJAH Orthopedic Hospital in Shropshire, United Kingdom.

"Our proteomic study has revealed that treatment of cultured cells with valproate causes reduced production of collagen, the main protein in bone, and osteonectin, which is required for maintenance of bone mass," writes lead investigator Glenn Morris, PhD, from the RJAH Orthopedic Hospitaland colleagues.

The findings are especially important for those with SMA, a rare genetic disease that causes loss of muscle control and movement, they noted.

"SMA patients may already suffer bone weakness as a result of SMN1 gene deletion, so further bone loss would be undesirable," the authors say in the study, which has been published online in the Journal of Proteome Research.

Valproate, which was introduced more than 40 years ago to prevent seizures in patients with epilepsy, is also commonly prescribed to treat several mood disorders, migraine headache, and SMA.

The long-term use of valproate is a possible side effect. However, the reason for the adverse reaction has been "a long-standing mystery," the researchers said.

The researchers studied more than 2000 cellular proteins of patients with SMA. "Using iTRAQ labeling technology, followed by 2-dimensional liquid chromatography and mass spectrometry analysis, a quantitative comparison of the proteome of an SMA cell line, with and without valproate treatment, was performed," the authors say.

Results showed that although most detectable proteins were unchanged after treatment with valproate, procollagen I peptides were decreased by 60 percent. "This decrease in procollagen I suggests that the effect of valproate is on collagen production in the fibroblasts rather than collagen matrix turnover," the authors say.

Production of collagen VI was also "substantially and significantly down-regulated by valproate treatment of cultured cells." They also found the levels of osteonectin, a collagen-binding glycoprotein, decreased by 28 percent.