07) when we also considered treatment with SSRIs, which was inversely correlated with trabecular BMD (p < 0.04). However, including SSRI treatment in the model did not alter the significant inverse association of prolactin with trabecular BMD in non-Hispanic white boys.

SSRIs were also negatively associated with lumbar BMD z score (p < 0.05), after accounting for Tanner stage, sex–age-adjusted height and weight z scores, daily intake of calcium, physical activity, and prolactin. Moreover, this association was moderated by variants of the serotonin transporter gene [Calarge et al. 2011]. Finally, several studies have reported elevations in alkaline phosphatase during AP treatment [Kumra Inhibitors,research,lifescience,medical et al. 1996, 1997; PD98059 purchase Erdogan et al. 2008; Pavuluri et al. 2010; Geller Inhibitors,research,lifescience,medical et al. 2012]. In children and adolescents, most

circulating alkaline phosphatase consists of the bone isoenzyme [Yang and Grey, 2006]. Therefore, an increase in the concentration of total alkaline phosphatase might reflect a direct effect of APs on bone turnover. This, however, cannot be confirmed (or ruled out) since the bone-specific isoenzyme was not measured in these studies. Alternatively, it is equally likely that the hepatic isoenzyme accounts for this increase due to AP-induced weight gain, potentially leading to steatosis, Inhibitors,research,lifescience,medical or due to direct hepatotoxicity [Kumra et al. 1996, 1997; Erdogan et al. 2008, 2010]. Discussion Most, albeit not all, APs exhibit a strong affinity for dopamine D2 receptors [Richelson and Souder, 2000]. By blocking these receptors in the anterior

pituitary, APs increase circulating prolactin. This, in turn, could interfere with bone metabolism through direct and indirect effects. In addition, APs may affect bone Inhibitors,research,lifescience,medical health via several other processes, including the modulation of serotoninergic and adrenergic signaling. In children and adolescents, impaired skeletal mineralization could have lasting consequences since bone mass acquired by young adulthood is a significant determinant of lifetime fracture risk [NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, Inhibitors,research,lifescience,medical 2001]. In general, when an AP is initiated, the immediate concern is symptom control. While APs might be predominantly used to Ribonucleotide reductase treat psychotic and severe mood disorders in adults, they are commonly used to treat explosive behavior in children and adolescents, in the context of disruptive behavior disorders, pervasive developmental disorders, mood disorders, or psychosis [Findling et al. 2008; Comer et al. 2010]. Therefore, optimizing the safety of the child and their environment is the absolute priority initially. It is when the acute circumstances dissipate and the child’s behavior improves that attention ought to focus on the long-term tolerability of the treatment. Unfortunately, extended use of APs is often necessary lest the underlying psychiatric symptoms return.