Chadi A Calarge, James A Mills, Kathleen F Janz, Trudy L Burns, Janet A Schlechte, William H Coryell, Babette S Zemel

To prospectively examine the independent contribution of major depressive disorder (MDD), generalized anxiety disorder (GAD), and selective serotonin reuptake inhibitors (SSRIs) use to changes in bone metabolism in older adolescents and emerging adults. Medically-healthy 15 to 20 year-olds who were unmedicated or within one month of starting an SSRI were prospectively followed. Psychiatric functioning and medication treatment were assessed monthly. Every four months, trabecular and cortical volumetric bone mineral density (vBMD) at the radius and markers of bone metabolism were evaluated. Every eight months, total body less head areal bone mineral content and lumbar spine (LS) areal BMD were determined. Linear mixed effects regression analysis examined associations between bone measures on the one hand and MDD, GAD, and SSRI indices on the other. Two hundred and sixty four participants were followed for 1.51 ± 0.76 years. After adjusting for age, sex, vitamin D concentration, physical activity, lean mass or grip strength, and time in the study, MDD severity was associated with increasing LS aBMD. Similarly, SSRI use was associated with increasing LS aBMD and bone formation in female participants. In contrast, SSRI use was associated with decreasing LS aBMD in males. After accounting for depression, GAD was independently, albeit weakly, associated with increased bone mineralization. In older adolescents and emerging adults, MDD and GAD are associated with increasing bone mass, particularly in the lumbar spine and in females, while SSRIs are associated with increasing bone mass in females but decreasing bone mass in males. This article is protected by copyright. All rights reserved.