The authors deleted estrogen receptor alpha (ERα) at different stages of differentiation in murine osteoblast lineage cells. They found that ERα in osteoblast progenitors expressing Osterix1 (Osx1) potentiates Wnt/β-catenin. This signaling pathway was required for optimal cortical bone accrual at the periosteum in mice. ERα expression in mature osteoblasts or osteocytes did not influence cancellous or cortical bone mass. Hence, the ERα functions to optimize bone mass at distinct bone compartments and in response to different cues.