Depression, Selective Serotonin Reuptake Inhibitors, and Osteoporosis

Abstract

An increasing number of studies suggest an association between depression and osteoporosis. In a mouse model, depression induces bone loss, mediated by brain-to-bone sympathetic signaling. Depression and bone antianabolic sympathetic tone are alleviated by increasing central serotonin (5-hydroxytryptamine, 5-HT) levels. However, selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants, increase extracellular 5-HT levels but have deleterious skeletal effects. The skeletal serotonergic system consists of 5-HT receptors and the 5-HT transporter (5-HTT) in osteoblasts and osteocytes. 5-HTT is a transmembrane protein targeted by SSRIs. 5-HT restrains osteoblastic activity, thus leading to bone loss. Apparently, the negative skeletal effects of the peripheral SSRI-induced increase in 5-HT outweighs the skeletal benefits resulting from the enhanced central 5-HT antidepressant and antisympathetic activity. Overall, major depression appears as an important risk factor for osteoporosis. However, antidepressants, mainly SSRIs, should be evaluated in view of the causal relationship between depression and bone loss, and vis-à-vis their skeletal adverse effects. Patients with depressive disorders should undergo a routine skeletal evaluation and receive timely antiosteoporotic therapy, especially when SSRI treatment is prescribed.

SSRI use and risk of fractures among perimenopausal women without mental disorders

“…This finding is consistent with results from studies involving patients with mental health disorders 22–28. The sustained higher risk among SSRI users is also consistent with the biological hypothesis that fractures associated with SSRI use can be at least partially attributed to antidepressant-related modulation of bone homeostasis in favour of osteoclastic activity, which may result in lower bone mineral density and higher risks of fractures 29. HRs were significantly different between cohorts only after the second year when we modelled risk without including lag and induction periods, suggesting as well that SSRIs may need several months to produce clinically meaningful cumulative effects on bone mineral density.…”

Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case–control studies

“…Previous reviews have summarized the association between SSRIs and fracture and have tried to address the inconsistent findings regarding this association [22][23][24][25][26]. However, these reviews have neither provided an overall estimation of the effect of SSRIs on fracture nor systematically reviewed the subgroups of study design, study location, sex, and controlled confounders.…”

“…and A.F.B.) independently by examining reference lists from the original studies [7-15, 19-21, 29] and review articles [22][23][24][25][26] obtained during the electronic search.…”

“…Some studies found a significant positive association between SSRI use and fracture risk [7,9,[12][13][14][15][19][20][21]; yet other studies found a nonsignificant association [8,11]. Several narrative reviews examined the inconsistent results; however, these reviews did not include meta-analyses of the results [22][23][24][25][26].…”

Chronic Psychological Stress as a Risk Factor of Osteoporosis

“…Recently, the association between chronic psychological stress and osteoporosis has been the subject of a growing body of research. The published literature, especially recent animal and human studies, showed that chronic psychological stress is a risk factor for developing osteoporosis [11][12][13][14][15]. In the present review, we aim to provide the current understanding of the relationship between chronic psychological stress and osteoporosis.…”