[Effect of SSRIs on bone metabolism]

SSRIs have been shown to affect bone health in adults, but this has been poorly studied in children. Given the frequency of SSRI prescription in children and adolescents, it is crucial to evaluate the impact of SSRIs on bone growth because the bone mass attained early in life is the most important predictor of a normal bone constitution. Experimental studies have demonstrated a direct functional role of serotonin in bone metabolism, independently of hyperprolactinemia or growth hormone levels. We have reviewed the literature on serotonin and bone metabolism, including experimental studies, clinical studies in adults as well as in the pediatric population.

Experimental studies have shown that 5-HT transporter (5-HTT) is expressed in all kind of bone cells and is highly specific of the 5-HT recapture. 5-HTT inhibition by the SSRIs in these cells affects their function in vitro. Even though a few studies have suggested exposure to SSRIs could be beneficial by an anabolic effect on the trabecular bone, more concluding studies have demonstrated that SSRIs negatively affect bone growth, resulting in a specific bone phenotype including a reduction in bone mass, an altered bone architecture, and decreased mechanical properties. This phenotype is most probably the consequence of a decrease in bone formation, rather than an increase in bone resorption and is a direct and dose-dependent effect. However, many aspects of this bone effect of 5-HTT inhibition need to be further clarified, including the signal ways for 5-HTT and 5-HT receptors, origins of 5-HT in bone, and methods to isolate the inhibitory effect of 5-HTT specifically on bone.

Metabolic and neuroendocrine side effects have been documented in children and adolescents taking SSRIs but the specific and direct effect of these molecules on bone metabolism has been poorly studied in this population. In adults, clinical studies have shown an association between the use of SSRIs and bone demineralization as well as reduction in bone mass, especially in the elderly and post-menopausal women. However, depression itself has been associated with a lower bone mass and increased risk of osteoporosis. In children, case reports show a decrease in growth due to a decreased secretion of growth hormone, but not by a direct effect. One cross-sectional study suggests a decrease in bone mass following SSRI treatment that is independent of variation in prolactin levels, but without elevation of fracture risk. These results, however, need to be replicated in further studies.

Our review shows that experimental studies have demonstrated the implication of the serotonin system in bone metabolism. Mice with genetic disruption of 5-HTT have a bone phenotype of decreased bone mass, altered architecture, and decreased mechanical properties. Clinical studies exploring the effect of SSRIs on bone metabolism are scarce in children. However, results in adults tend to show a deleterious effect in the elderly. Regarding the frequency of SSRI prescription in the pediatric population, it is becoming urgent to better explore the effect of SSRIs on bone growth of children, as it can have major implications on the ulterior follow-up and on the precautions to take.