title: Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. b.m.verdel@uu.nl
authors.forename: Bertha Maria
authors.initials: BM
authors.lastname: Verdel
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Souverein
authors.forename: Toine C G
authors.initials: TC
authors.lastname: Egberts
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: van Staa
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000009:adverse effects*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D016022:Case-Control Studies; D003863:Depression / Q000188:drug therapy; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000139:chemically induced*; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors