Serotonin reuptake inhibitors may increase the risk of osteoporosis

Remodelling of the skeleton is initiated by multinucleated osteoclasts resorbing either trabecular or cortical bone. Termination of the resorptive phase is followed by new bone formation by osteoblasts. Under normal conditions, remodeling is balanced and bone mass is preserved, with the amount of new bone formed equaling the amount that was initially resorbed. Skeletal remodeling is thought to be controlled by several hormones and many different cytokines. Recent studies have indicated that signaling molecules found in the nervous system may also play an important role in bone remodeling. One of these signaling molecules is thought to be serotonin (5-hydroxytryptamin; 5-HT). Osteoblasts and osteoclasts have receptors for serotonin and both cells express the membrane protein that is responsible for serotonin reuptake (5-HTT). Gene knockout studies in mice and use of selective serotonin reuptake inhibitors (SSRls) in mice and humans have suggested that inhibition of 5-HTT leads to reduced bone mass. These observations raise the possibility that patients treated with SSRIs may have an increased risk for secondary osteoporosis and skeletal fractures.