Rates of bone loss among women initiating antidepressant medication use in midlife

Abstract

Context: Concern has been raised that medications that block serotonin reuptake may affect bone metabolism, resulting in bone loss.

Objective: The aim of the study was to compare annual bone mineral density (BMD) changes among new users of selective serotonin reuptake inhibitors (SSRIs), new users of tricyclic antidepressants (TCAs), and nonusers of antidepressant medications.

Design and setting: We conducted a prospective cohort study at five clinical centers in the United States.

Participants: The study included 1972 community-dwelling women, aged 42 years and older, enrolled in the Study of Women's Health Across the Nation (SWAN).

Exposure: The use of antidepressant medications was assessed by interview and verified from medication containers at annual visits. Subjects were categorized as nonusers (no SSRI or TCA use at any examination), SSRI users (initiated SSRI use after the baseline SWAN visit), or TCA users (initiated TCA use after the baseline visit), using a computerized dictionary to categorize type of medication.

Main outcome measures: BMD at the lumbar spine, total hip, and femoral neck was measured using dual-energy x-ray absorptiometry at annual visits.

Results: BMD was compared among 311 new users of SSRIs, 71 new users of TCAs, and 1590 nonusers. After adjustment for potential confounders, including age, race, body mass index, menopausal status, and hormone therapy use, mean lumbar spine BMD decreased on average 0.68% per year in nonusers, 0.63% per year in SSRI users (P = .37 for comparison to nonusers), and 0.40% per year in TCA users (P = .16 for comparison to nonusers). At the total hip and femoral neck, there was also no evidence that SSRI or TCA users had an increased rate of bone loss compared with nonusers. Results were similar in subgroups of women stratified by the Center for Epidemiologic Studies Depression Scale (<16 vs ≥16).

Conclusions: In this cohort of middle-aged women, use of SSRIs and TCAs was not associated with an increased rate of bone loss at the spine, total hip, or femoral neck.

Figure 1.

Study cohort.

Figure 2.

Mean annualized change in BMD by category of antidepressant use. A, Base model at all sites adjusted for age, site, menopausal status, race, and BMI. B, Multivariable model at each site. Spine: Base model + HT, physical activity, osteoporosis, thiazide use, menopausal stage*category of antidepressant use, HT*category of antidepressant use. Femoral neck: Base model + HT, osteoporosis, thiazide use, menopausal stage*category of antidepressant use. Total hip: Base model + HT, osteoporosis, thiazide use, menopausal stage*category of antidepressant use, diabetes, CES-D. *, P = .005 for comparison between SSRI users and non-users. HT, hormone therapy use.

Figure 3.

Mean annualized change in BMD by category of antidepressant use in cohort censoring users of bone active medications. A, Base model at all sites adjusted for age, site, menopausal status, race, and BMI, censored for use of bone active medications. B, Multivariable model at each site, censored for use of bone active medications. Spine: Base model +, physical activity, osteoporosis, menopausal stage*category of antidepressant use. Femoral neck: Base model + osteoporosis, menopausal stage*category of antidepressant use. Total hip: Base model + menopausal stage*category of antidepressant use, diabetes, CES-D. *, P = .03 for comparison between SSRI users and nonusers.