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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

Similar to the results for stiffness, the anticonvulsants significantly reduced the load to yield in femurs. **P<0.005 vs control. CA, carbamazepine; CC, controls; FL, fluoxetine; IM, imipramine; SA, saline; VA, valproate.
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fig3: Similar to the results for stiffness, the anticonvulsants significantly reduced the load to yield in femurs. **P<0.005 vs control. CA, carbamazepine; CC, controls; FL, fluoxetine; IM, imipramine; SA, saline; VA, valproate.

Mentions: In general, anticonvulsant drug therapy causes a decrease in mechanical properties of whole bones. Both the VAL and CBZ groups exhibited significant decreases in stiffness and yield load (see Figures 2 and 3). The VAL group exhibited an 18.5% reduction in stiffness and a 25.3% reduction in yield load when compared with the SAL group. Treatment with CBZ resulted in a 21.3% decrease in stiffness and 26.5% decrease in yield load when compared with the CBZ-V group. Similar trends were seen in failure load results, although the comparison was only statistically significant between the CBZ and CBZ-V groups.


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)

Similar to the results for stiffness, the anticonvulsants significantly reduced the load to yield in femurs. **P<0.005 vs control. 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

fig3: Similar to the results for stiffness, the anticonvulsants significantly reduced the load to yield in femurs. **P<0.005 vs control. CA, carbamazepine; CC, controls; FL, fluoxetine; IM, imipramine; SA, saline; VA, valproate.
Mentions: In general, anticonvulsant drug therapy causes a decrease in mechanical properties of whole bones. Both the VAL and CBZ groups exhibited significant decreases in stiffness and yield load (see Figures 2 and 3). The VAL group exhibited an 18.5% reduction in stiffness and a 25.3% reduction in yield load when compared with the SAL group. Treatment with CBZ resulted in a 21.3% decrease in stiffness and 26.5% decrease in yield load when compared with the CBZ-V group. Similar trends were seen in failure load results, although the comparison was only statistically significant between the CBZ and CBZ-V groups.

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