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Type: Journal article
Title: Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications
Author: Gold, P.
Pavlatou, M.
Michelson, D.
Mouro, C.
Kling, M.
Wong, M.
Licinio, J.
Goldstein, S.
Citation: Translational Psychiatry, 2015; 5(6):e576-1-e576-6
Publisher: Nature Publising Group
Issue Date: 2015
ISSN: 2158-3188
Statement of
PW Gold, MG Pavlatou, D Michelson, CM Mouro, MA Kling, M-L Wong, J Licinio and SA Goldstein
Abstract: Major depression and bipolar disorder are associated with decreased bone mineral density (BMD). Antidepressants such as imipramine (IMIP) and specific serotonin reuptake inhibitors (SSRIs) have been implicated in reduced BMD and/or fracture in older depressed patients. Moreover, anticonvulsants such as valproate (VAL) and carbamazepine (CBZ) are also known to increase fracture rates. Although BMD is a predictor of susceptibility to fracture, bone strength is a more sensitive predictor. We measured mechanical and geometrical properties of bone in 68 male Sprague Dawley rats on IMIP, fluoxetine (FLX), VAL, CBZ, CBZ vehicle and saline (SAL), given intraperitoneally daily for 8 weeks. Distinct regions were tested to failure by four-point bending, whereas load displacement was used to determine stiffness. The left femurs were scanned in a MicroCT system to calculate mid-diaphyseal moments of inertia. None of these parameters were affected by antidepressants. However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness. Only CBZ induced alterations in mechanical properties that were accompanied by significant geometrical changes. These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment. Thus, decreased BMD and increased fracture rates in older patients on antidepressants are more likely to represent factors intrinsic to depression that weaken bone rather than antidepressants per se. Patients with affective illness on anticonvulsants may be at particularly high risk for fracture, especially as they grow older, as bone strength falls progressively with age.
Keywords: Bipolar disorder; depression; drug therapy; musculoskeletal abnormalities
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
RMID: 0030048359
DOI: 10.1038/tp.2015.38
Appears in Collections:Medicine publications

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