New research shows that selective serotonin-reuptake inhibitors (SSRIs) affect bone remodelling via two distinct mechanisms. In the short term (3 weeks), fluoxetine (the active compound in Prozac), has local anti-resorptive properties and increases bone volume. However, long-term treatment (6 weeks) offset the initial anti-resorptive effect and resulted in bone loss. Importantly, co-treatment with the β-blocker propranolol prevented the long-term effects of fluoxetine and, thus, bone loss. The findings highlight a possible strategy to counteract the increased risk of fractures with SSRI use.