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

Bertha Maria Verdel*, Patrick C Souverein, Toine C G Egberts, Tjeerd P van Staa, Hubert G M Leufkens, Frank de Vries

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)604-9
Number of pages6
Issue number3
Publication statusPublished - Sept 2010
Externally publishedYes


  • 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
  • Serotonin Plasma Membrane Transport Proteins/metabolism
  • Serotonin Uptake Inhibitors/adverse effects
  • Young Adult


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