Current Osteoporosis Reports

, Volume 8, Issue 4, pp 185–191 | Cite as

Depression, Selective Serotonin Reuptake Inhibitors, and Osteoporosis

  • Itai BabEmail author
  • Raz Yirmiya


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.


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 



No potential conflicts of interest relevant to this article were reported.


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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Bone LaboratoryThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.Department of Psychology, Faculty of Social SciencesThe Hebrew University of JerusalemJerusalemIsrael

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