title: Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications.
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.
authors.affiliation: Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Gold
authors.affiliation: Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Pavlatou
authors.affiliation: Merck, Whitehouse Station, NJ, USA.
authors.forename: D
authors.initials: D
authors.lastname: Michelson
authors.affiliation: Orthopaedic Research Laboratories, University of Michigan, Ann Arbor, MI, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Mouro
authors.affiliation: 1] Behavioral Health Service, Philadelphia VA Medical Center, Philadelphia, PA, USA [2] Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Kling
authors.affiliation: Department of Translational Medicine, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
authors.forename: M-L
authors.initials: ML
authors.lastname: Wong
authors.affiliation: Department of Translational Medicine, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Licinio
authors.affiliation: Orthopaedic Research Laboratories, University of Michigan, Ann Arbor, MI, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D002220:Carbamazepine / Q000494:pharmacology; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology; D055114:X-Ray Microtomography
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D005473:Fluoxetine; D002220:Carbamazepine; D014635:Valproic Acid; D007099:Imipramine