Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men

Arch Intern Med. 2007 Jun 25;167(12):1246-51. doi: 10.1001/archinte.167.12.1246.


Background: Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of antidepressants that block the serotonin transporter. Osteoblasts and osteocytes express functional serotonin transporters; serotonin transporter gene disruption in mice results in osteopenia; and SSRI use has been associated with increased risk of hip fracture.

Methods: To determine whether SSRI use is associated with lower bone mineral density (BMD) in older men and to compare the results for SSRIs with those of other antidepressants, we performed a cross-sectional analysis of data from 5995 men 65 years and older participating in the prospective cohort Osteoporotic Fractures in Men Study. Main outcome measures included medication use; BMD at the femoral neck, greater trochanter, and lumbar spine measured by dual-energy x-ray absorptiometry; and potential covariates.

Results: In adjusted analyses, mean BMD among SSRI users (n=160) was 3.9% lower at the total hip and 5.9% lower at the lumbar spine compared with BMD in men reporting no antidepressant use (n=5708 [P=.002 for total hip; P<.001 for lumbar spine]). There was no significant difference among users of trazodone hydrochloride (n=52) or tricyclic antidepressants (n=99) compared with nonusers. Adjusting for variables that could be associated with BMD and/or SSRI use did not significantly alter these results. The observed difference in BMD for SSRIs is similar to that seen with glucocorticoids.

Conclusions: In this population of men, BMD was lower among those reporting current SSRI use, but not among users of other antidepressants. Further research is needed to confirm this finding in light of widespread SSRI use and potentially important clinical implications.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Bone Density / drug effects*
  • Cross-Sectional Studies
  • Depression / drug therapy
  • Femur Neck / diagnostic imaging
  • Follow-Up Studies
  • Fractures, Bone / diagnostic imaging
  • Fractures, Bone / epidemiology
  • Fractures, Bone / etiology*
  • Hip / diagnostic imaging
  • Humans
  • Incidence
  • Lumbar Vertebrae / diagnostic imaging
  • Male
  • Middle Aged
  • Osteoporosis / chemically induced*
  • Osteoporosis / complications
  • Osteoporosis / metabolism
  • Prospective Studies
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • United States / epidemiology


  • Serotonin Uptake Inhibitors