Background: Selective serotonin reuptake inhibitors (SSRIs) are considered as a principal
treatment for depression. They might exhibit a skeletal effect due to the existence of functioning
serotonergic pathways in the bone evidenced by its harmful effects in the postmenopausal
period. It was shown previously that leptin is involved in bone turnover regulation. Objective:
The purpose of the present study was to investigate the effects of sertraline (an SSRI) on bone
turnover of female rats, leptin involvement and its independence of that effect on estrogen.
Method: Groups of bilaterally ovariectomized (performed 4weeks before starting treatment) &
non-ovariectomized Wistar rats received sertraline (10&20mg/kg) for 4 weeks. Serum estradiols,
serum osteocalcin, urinary hydroxyproline, mineral content of femur, serum leptin, and
hypothalamic leptin receptor mRNA expression as well as histopathological studies were
assessed. Results: The results showed sertraline increased bone turnover and decreased bone
mineral content in both non-ovariectomized and ovariectomized rats. It also decreased the level
of leptin peripherally as well as the hypothalamic leptin receptor mRNA expression in both OVX
& NOVX groups. Conclusion: These findings suggest that SSRIs, which are frequently
prescribed as antidepressants, have an undesirable impact on bone, which is probably not
dependent on estrogen. Moreover, sertraline modulates leptin level centrally and peripherally,
indicating its mechanistic involvement. Received in original form: 17 August 2022 Accepted in a final form: 26 September 2022