An Approach to Preventing SSRI-Induced Bone Loss?

Chronic use of some selective serotonin reuptake inhibitors (SSRIs) causes bone loss and predisposes to fractures. To determine why, investigators conducted a series of in vitro experiments and in vivo studies of mice exposed to therapeutic levels of fluoxetine for 3 or 6 weeks.

After the shorter period of exposure, the authors identified a nonserotonergic mechanism involving alteration of a calcium–calmodulin cascade that led to altered activity of a transcription factor. This cascade resulted in decreased osteoclast production and less preservation of bone. After 6 weeks, increased synaptic serotonin in the hypothalamus desensitized 5-HT2 receptors, with the result that hypothalamic activation of the sympathetic nervous system was disinhib…