Depression, selective serotonin reuptake inhibitors and osteoporosis

Itai Bab*, Raz Yirmiya

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

39 Scopus citations


An increasing number of studies suggest an association between depression and osteoporosis. In a mouse model, depression induces bone loss, mediated by brain-to-bone sympathetic signaling. Depression and bone antianabolic sympathetic tone are alleviated by increasing central serotonin (5-hydroxytryptamine, 5-HT) levels. However, selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants, increase extracellular 5-HT levels but have deleterious skeletal effects. The skeletal serotonergic system consists of 5-HT receptors and the 5-HT transporter (5-HTT) in osteoblasts and osteocytes. 5-HTT is a transmembrane protein targeted by SSRIs. 5-HT restrains osteoblastic activity, thus leading to bone loss. Apparently, the negative skeletal effects of the peripheral SSRI-induced increase in 5-HT outweighs the skeletal benefits resulting from the enhanced central 5-HT antidepressant and antisympathetic activity. Overall, major depression appears as an important risk factor for osteoporosis. However, antidepressants, mainly SSRIs, should be evaluated in view of the causal relationship between depression and bone loss, and vis-à-vis their skeletal adverse effects. Patients with depressive disorders should undergo a routine skeletal evaluation and receive timely antiosteoporotic therapy, especially when SSRI treatment is prescribed.

Original languageAmerican English
Pages (from-to)185-191
Number of pages7
JournalCurrent Osteoporosis Reports
Issue number4
StatePublished - Dec 2010


  • Adrenergic signaling
  • Antidepressant
  • Bone loss
  • Bone mass
  • Bone remodeling
  • Depression
  • Fracture
  • Glucocorticoids
  • Major depressive disorder
  • Norepinephrine
  • Osteoblast
  • Osteocyte
  • Osteoporosis
  • Selective serotonin reuptake inhibitors
  • Serotonin
  • Serotonin receptors
  • Serotonin transporter
  • Sympathetic nervous system


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