Effects of Deletion of ER[alpha] in Osteoblast-Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice

Estrogen receptor alpha (ER[alpha]) has been implicated in bone's response to mechanical loading in both males and females. ER[alpha] in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ER[alpha] is deleted. We demonstrated previously that when ER[alpha] is deleted from mature osteoblasts and osteocytes in mixed-background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell-specific ER[alpha]KO mice. Therefore, we crossed ER[alpha] floxed (ER[alpha]fl/fl) and osteocalcin-Cre (OC-Cre) mice to generate animals lacking ER[alpha] in mature osteoblasts and osteocytes (pOC-ER[alpha]KO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro-CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ER[alpha] in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC-ER[alpha]KO mice had decreased cortical and cancellous bone mass, whereas male pOC-ER[alpha]KO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC-ER[alpha]KO female L5 vertebrae and with increased maximum moment in pOC-ER[alpha]KO male femora. Female pOC-ER[alpha]KO mice responded more to mechanical loading, whereas the response of pOC-ER[alpha]KO male animals was similar to their littermate controls. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.