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Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications.

Gold PW, Pavlatou MG, Michelson D, Mouro CM, Kling MA, Wong ML, Licinio J, Goldstein SA - Transl Psychiatry (2015)

Bottom Line: Major depression and bipolar disorder are associated with decreased bone mineral density (BMD).However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness.These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

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.

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Related in: MedlinePlus

Anticonvulsant drug therapy demonstrated a significant decrease in whole bone stiffness. +P=0.055 vs SA. *P<0.05 vs CC. CA, carbamazepine; CC, controls; FL, fluoxetine; IM, imipramine; SA, saline; VA, valproate.
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fig2: Anticonvulsant drug therapy demonstrated a significant decrease in whole bone stiffness. +P=0.055 vs SA. *P<0.05 vs CC. CA, carbamazepine; CC, controls; FL, fluoxetine; IM, imipramine; SA, saline; VA, valproate.

Mentions: Three months of daily treatment with IMIP and FLX had no impact on stiffness, bone yield or geometric properties of bone consisting of moment of inertia, cortical thickness and cross-sectional area (Figure 2).


Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications.

Gold PW, Pavlatou MG, Michelson D, Mouro CM, Kling MA, Wong ML, Licinio J, Goldstein SA - Transl Psychiatry (2015)

Anticonvulsant drug therapy demonstrated a significant decrease in whole bone stiffness. +P=0.055 vs SA. *P<0.05 vs CC. CA, carbamazepine; CC, controls; FL, fluoxetine; IM, imipramine; SA, saline; VA, valproate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490276&req=5

fig2: Anticonvulsant drug therapy demonstrated a significant decrease in whole bone stiffness. +P=0.055 vs SA. *P<0.05 vs CC. CA, carbamazepine; CC, controls; FL, fluoxetine; IM, imipramine; SA, saline; VA, valproate.
Mentions: Three months of daily treatment with IMIP and FLX had no impact on stiffness, bone yield or geometric properties of bone consisting of moment of inertia, cortical thickness and cross-sectional area (Figure 2).

Bottom Line: Major depression and bipolar disorder are associated with decreased bone mineral density (BMD).However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness.These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

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.

Show MeSH
Related in: MedlinePlus