Purpose: To investigate the effect of antidepressants on bone mineral density and bone metabolism in ovariectomized rats with depression. Methods: 48 female rats were randomly and equally assigned to six groups, namely, sham (Sn), ovariectomized depression (OD), ovariectomized depression rats treated with sertraline (ODs), citalopram (ODx), reboxetine (ODr), and venlafaxine groups (ODw). Behavioral alterations and bone-related parameters were evaluated before and after treatment. Results: After treatment, ODs, ODx, ODw, and ODr groups had higher levels of horizontal and vertical exercise scores, sugar water consumption, osteoclasts, and serum CTX-1 (p < 0.05) compared to OD group. Osteocytes, serum serotonin (5-HT), osteocalcin (BGP), and type I procollagen N-terminal propeptide (PINP) were significantly decreased (p < 0.05) after treatment in ODs, ODx, ODw, and ODr groups. A positive correlation was observed between 5-HT, BGP, PINP, and whole-body bone mineral density (r = 0.931, 0.907, and 0.843, p < 0.05) respectively, while a negative correlation was observed between collagen type I C-terminal propeptide (CTX-I) and bone mineral density (r = -0.855, p < 0.05). Conclusion: Antidepressants reduce bone mineral density and osteocyte proliferation, while increasing osteoclast proliferation. These effects are associated with reductions in 5-HT, PINP and BGP levels, and increase in CTX-I.
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