Osteocalcin is a bone-derived hormone that regulates a growing number of physiological functions. Osteocalcin-/- mice have increased anxiety-like behavior and depression, decreased exploratory behavior, and impaired learning and memory. Given that osteocalcin is produced only by osteoblasts, Khrimian et al. asked whether an impairment in osteoblast differentiation and function, as may occur in various skeletal dysplasias or with aging, could affect cognition or anxiety. Their results suggest that a decrease in osteocalcin is indeed the cause for these cognitive impairments.