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.
Highlights
Other studies report that both specific serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) increase the risk of hip fracture in older patients without commenting on bone mineral density (BMD).[4,5,6]
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)
Similar trends were seen in failure load results, the comparison was only statistically significant between the CBZ and carbamazepine vehicle (CBZ-V) groups
Summary
Recent data in large populations of older individuals indicate that specific serotonin reuptake inhibitors (SSRIs) are associated with the risk of decreased bone mineral density (BMD) and/or hip fracture.[1,2,3] Other studies report that both SSRIs and tricyclic antidepressants (TCAs) increase the risk of hip fracture in older patients without commenting on BMD.[4,5,6] The impact of antidepressants on BMD is complicated by the fact that many papers find that major depression is associated with loss of BMD per se.[7,8,9] This loss of BMD in patients with major depression potentially reflects a number of hormonal alterations that may be risk factors for decreased BMD, including hypercortisolism, decreased secretion of growth hormone and hypothalamic hypogonadism.[10,11,12] In addition, melancholic patients with major depression have around-the-clock increases in plasma and CSF norepinephrine secretion,[13] and recent data indicate that sympathetic drive contributes to bone loss.[14]. In our premenopausal women with major depression, bone loss was considerably greater at the hip than at the spine,[7] in contrast to the usual pattern of greater loss of vertebral bone in common forms of osteoporosis. This pattern is more compatible with inflammatory causes of osteoporosis. Inflammation may be important in the bone loss of depressive illness
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
