Sertraline’s deleterious effect on bone turnover in ovariectomized rats: The potential role of leptin, independent of estrogen.

Abstract

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.