IBMS BoneKEy | Perspective
Depression, selective serotonin re-uptake inhibitors and the regulation of bone mass
Itai Bab
Raz Yirmiya
DOI:10.1138/20090357
Abstract
An increasing number of studies suggests that low bone mineral density (BMD) is disproportionately prevalent among patients with depressive disorders. However, authorities such as the National Institutes of Health, the National Osteoporosis Foundation, the National Osteoporosis Society (UK) and Osteoporosis Canada, have not yet officially acknowledged depression as a risk factor for osteoporosis. This could be because the causal relationship between depression and low bone mass has not been fully elucidated. In a recent study using a mouse model for depression we have demonstrated a causal relationship between depressive-like behavior and bone loss, which could be prevented by an antidepressant. The depression-induced bone loss was associated with increases in skeletal norepinephrine and serum corticosterone levels. Bone loss, but not the depressive behavior, could be blocked by a β-blocker, portraying an important role for adrenergic signaling in communicating depressive signals to the skeleton. For an unknown reason, selective serotonin re-uptake inhibitors (SSRIs), which have emerged as first-line agents in the treatment of depressive disorders, appear to have deleterious skeletal effects in both humans and experimental animals. The antidepressant effect of SSRIs is attributed to increased serotonin levels. Hence, their negative skeletal effect has to be evaluated not only in view of the causal relationship between depression and bone loss, but also vis-à-vis the presence of a skeletal serotonergic system, the stimulation of bone formation and bone density by exogenously administered serotonin and the paradoxical negative regulation of bone formation and bone mass by serum, gut-derived serotonin. Physicians should be aware of the unfavorable consequences of SSRIs on BMD and fracture risk.
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