**9.1 Pathophysiology of serotonin reuptake inhibitors and bone health**

Besides hypothalamic–pituitary–adrenal (HPA) axis dysregulation and other hormonal abnormalities, MDD-related lifestyle factors such as poor diet, lack of physical activity, and smoking may also contribute to bone mineralization problems [103, 106–109]. Psychotropic medications, especially selective serotonin reuptake inhibitors (SSRI), can also increase fracture risks [103–106]. Serotonin receptors, neurotransmitters, and transporters have been discovered in osteoblasts and osteoclasts since 2001. Gut bacteria synthesize 95% of serotonin [97, 110, 111]. Gut and brain serotonin was found to have different actions on the bone metabolism by acting through different pathways as follows [112]:

