Histone deacetylase 3 is required for maintenance of bone mass during aging

► Deleting Hdac3 in mature osteoblasts with Osteocalcin-Cre (Hdac3 CKOOCN) caused progressive cortical and trabecular bone loss with age. ► Cortical bone mineralization and material properties were compromised in Hdac3 CKOOCN as compared to control mice. ► Bone loss in Hdac3 CKOOCN mice was attributed to decreased bone formation and osteoblast/osteocyte function. ► Hdac3 deletion caused DNA damage in osteoblasts and osteocytes in vitro and in vivo. ► Chondrocyte activity and growth plate development were not affected in Hdac3 CKOOCN mice.