Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: Evidence from clinical studies

Elizabeth M. Haney, S. J. Warden

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


The discovery of a functional serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) in bone has given rise to questions about the physiologic role of 5-HT in bone, and the possible clinical implications for humans. 5-HT is known to play a role in the pathophysiology of depression, and many antidepressant medications function by inhibiting the 5-HIT. Among the antidepressants, those that selectively block the 5-HTT (namely, selective serotonin reuptake inhibitors; SSRIs) appear to have skeletal effects. Several studies have demonstrated lower bone density, increased rates of bone loss at the hip, and increased rates of fracture among older individuals taking SSRIs. However, there remains uncertainty about whether it is the antidepressant medications themselves or the reason for their use (depression) that is responsible for these observed bone changes. This paper reviews the epidemiologic literature that explores the role of the 5-HTT in bone health, by looking at questions about how depression, antidepressant therapy and SSRIs impact bone health in humans. Further research will be important to better understand how these factors interact to influence skeletal status, and to characterize the biochemical mechanism through which 5-HT may mediate bone turnover and metabolism.

Original languageEnglish (US)
Pages (from-to)133-145
Number of pages13
JournalJournal of Musculoskeletal Neuronal Interactions
Issue number2
StatePublished - Jun 2008


  • Bone density
  • Depression
  • Fracture
  • Osteoporosis
  • Selective serotonin reuptake inhibitors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Orthopedics and Sports Medicine


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