**9. Serotonin reuptake inhibitors and bone health**

Anhedonia, insomnia, anorexia, fatigue, and cognitive dysfunction are symptoms of major depressive disorder (MDD). Osteoporosis and fractures are more likely to occur in people with MDD [91–94].

SSRIs are associated with an increased fracture risk compared to nonusers, according to a number of observational studies [95–98]. Comparing 124,655 fracture cases with 373,962 controls, Danish national registers found that the use of SSRIs increased the risk of hip and vertebral fractures [99–102]. A Dutch study found that SSRI use was associated with an early increase in fracture risk, which peaked within 8 months of use but decreased after discontinuation. The risk of fracture among old patients taking SSRIs is almost threefold in Taiwanese case– control studies [103].

In a cross-sectional study of 5995 patients, SSRIs significantly reduced hip BMD (4%) and spine BMD (6%) compared with nonusers. This was further confirmed in a cohort study of nearly 3000 women divided into three groups: SSRI users

(198), tricyclic antidepressants (TCA) users (118), and nonusers (2406). After 5 years, SSRI users had the greatest bone loss (0.8% decrease in BMD). Rauma et al. reported reduced BMD in 928 men receiving SSRIs or SNRIs, but not in TCAs users [102, 104, 105].
