Editors' ChoiceDEPRESSION

Sympathetic to Osteoporosis

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Science's STKE  14 Nov 2006:
Vol. 2006, Issue 361, pp. tw384
DOI: 10.1126/stke.3612006tw384

Major depression is associated with decreased bone mineral density (indicative of osteoporosis) and an increased risk for osteoporotic fractures. The precise relationship between depression and osteoporosis, however, has been unclear, leading Yirmiya et al. to investigate the effects on mouse skeleton of chronic mild stress (CMS), a rodent model of depression. Mice subjected to CMS experienced decreased bone mass and a reduced rate of bone formation in parallel with behavioral effects such as decreased preference for sucrose (comparable to human anhedonia) and reduced social exploration. Treatment with the tricyclic antidepressant imipramine attenuated both the behavioral effects of CMS and bone loss. Moreover, mice that failed to respond to imipramine behaviorally also failed to show an attenuation of bone loss. Body weight, locomotor activity, and serum testosterone were unaffected by CMS. Serum corticosterone was higher in mice exposed to CMS; however, adrenalectomized mice failed to show either behavioral responses to CMS or bone loss, making the role of corticosteroids in mediating depression-induced loss of bone mass difficult to evaluate. The content of sympathetically derived norepinephrine in trabecular bone was increased in CMS mice, and treatment with the β-adrenergic receptor propanolol, which failed to affect the behavioral response to CMS, markedly attenuated the CMS-induced decrease in bone mass and inhibition of bone formation. Thus, the authors conclude that depression leads to bone loss through sympathetic release of norepinephrine and that, in individuals at risk for both, antidepressants could be used to combat not only depression but also osteoporosis.

R. Yirmiya, I. Goshen, A. Bajayo, T. Kreisel, S. Feldman, J. Tam, V. Trembovler, V. Csernus, E. Shohami, I. Bab, Depression induces bone loss through stimulation of the sympathetic nervous system. Proc. Natl. Acad. Sci. U.S.A. 103, 16876-16881 (2006). [Abstract] [Full Text]

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