Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures

Bone. 2010 Sep;47(3):604-9. doi: 10.1016/j.bone.2010.06.006. Epub 2010 Jun 18.


Aim: Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures. The serotonin transporter (5-HTT) has been located in the bone and may play a role in bone physiology. We assessed the association between antidepressant drug use, categorized in a therapeutical-based way and on basis of their affinity for the 5-HTT, and the risk of both osteoporotic and non-osteoporotic fractures.

Methods: A case-control study was conducted using the PHARMO RLS. Cases were patients with a first hospital admission for a fracture during the study period. Up to four controls were matched to each case on gender, age, geographical area, and index date.

Results: We identified 16,717 cases, of whom 59.5% had an osteoporotic fracture, and 61,517 controls. Compared to no use, current use of SSRIs was associated with a statistically significant increased risk of osteoporotic fractures (OR 1.95, 95% CI 1.69-2.26), as was current use of TCAs and non-SSRI/non-TCA antidepressant drugs (ORs 1.37, 95% CI 1.16-1.63 and 1.40, 95% CI 1.06-1.85, respectively). The risk of an osteoporotic fracture was statistically significantly higher for antidepressants with a high affinity for the 5-HTT (OR 1.86, 95% CI 1.63-2.13) compared to antidepressants with a medium or low affinity (OR 1.43, 95% CI 1.19-1.72 (medium) and OR 1.32 95% CI 0.98-1.79 (low) (p<0.05 for trend). The risk of non-osteoporotic fractures did not show the same trend.

Conclusions: The extent of affinity for the 5-HTT may contribute to the increased risk of osteoporotic fractures related to antidepressant drug use. The pharmacological mechanism-based classification could to be an appropriate alternative for traditional classification to study the association between the use of antidepressants and the risk of fractures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Case-Control Studies
  • Depression / drug therapy
  • Fractures, Bone / chemically induced*
  • Humans
  • Middle Aged
  • Osteoporotic Fractures / chemically induced*
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Young Adult


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors