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The use of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants among women in midlife didn't lead to a greater rate of bone loss, a prospective cohort study found.

Among women enrolled in the longitudinal , yearly decrease in bone mineral density (BMD) at the lumbar spine averaged 0.63% in new users of SSRIs compared with 0.68% in those not taking antidepressants (P=0.37), according to Susan J. Diem, MD, of the University of Minnesota in Minneapolis, and colleagues.

And among those taking the tricyclic antidepressants, the annual lumbar spine BMD decrease was 0.40% (P=0.16 compared with nonusers),

"Theidentification of , osteocytes, and osteoclasts has suggested a role for serotonin in the regulation of bone metabolism and raised the possibility that SSRIs may have an effect on bone health," they observed.

, and in design and populations.

It's been estimated that more than 20% of U.S. women in their 40s and 50s take antidepressants. To address the question of whether those drugs are likely to have a negative effect on their long-term bone health, Diem and colleagues analyzed the rate of change in BMD over the course of 6 years among 1,972 women whose mean age was 50.

During the follow-up period, 311 women began taking SSRIs, 71 started therapy with tricyclic antidepressants, and 1,590 used no antidepressants.

After adjusting for age, race, body mass index, and menopausal status, women using SSRIs had no higher annual rate of bone loss at the spine (-0.67% versus -0.72%, P=0.36) or femoral neck (-0.70% versus -0.75%, P=0.49) than those not using antidepressants, and had lower mean BMD loss at the total hip (-0.35% versus -0.47%, P=0.005).

Further adjustment for depression scores and vasomotor symptoms didn't change the results, but in a final multivariate analysis that included factors such as vitamin D and calcium supplementation, smoking and alcohol use, social support, and comorbidities, the only difference was a loss of significance for the BMD at the total hip.

Women taking tricyclic antidepressants also had no greater annual bone loss at the spine compared with nonusers (-0.35% versus -0.72%, P=0.10). In addition, tricyclic users had nonsignificantly lower bone loss at the total hip and femoral neck.

On a secondary analysis that excluded women taking hormones, steroids, bisphosphonates, or thiazide diuretics, there once again was no evidence of increased bone loss for SSRI users.

An additional secondary analysis that stratified women according to severity of depression on the , there was no difference for women scoring high enough to suggest clinically significant depression.

Two previous studies looked at changes in BMD among users of SSRIs. In one, in which patients' mean age was 80, there was an association between bone loss and these medications, while the other, from the , found no link.

The present study has certain strengths compared with those earlier studies, the researchers noted, in that participants were seen each year so there were frequent BMD measurements and report of medication use.

In addition, because only new users of the drugs were included, confounding through inclusion of prevalent users was avoided.

However, confounding by indication is a possibility, because depression has previously been shown to have an association with bone loss and fracture risk.

"A large body of work has reported , an outcome not assessed in the present analysis," the researchers observed. "Our findings suggest that if antidepressant use is associated with fracture risk, the mechanism of that association is not due to effects of the medications on BMD."

This study "should provide reassurance" for women considering antidepressant treatment as they transition through menopause, they noted.

"Although initiating pharmacological therapy always requires careful balance of potential risks and benefits of the treatment, these results suggest that SSRIs and [tricyclic antidepressants] do not appear to have adverse effects on BMD in women in this age group," Diem and colleagues concluded.

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