Bone mass and adaptation to mechanical loading are sexually dimorphic in adult osteoblast-specific ERα knockout mice

Estrogen receptor-alpha (ER alpha) regulates bone mass and is implicated in bone tissue's response to mechanical loading. The effects of ER alpha deletion in mice depend on sex, anatomical location, and the cellular stage at which ER alpha is removed. Few studies have investigated the effect of age on the role of ER alpha in skeletal maintenance and functional adaptation. We previously demonstrated that bone mass and adaptation to loading were altered in growing 10-week-old female and male mice lacking ER alpha in mature osteoblasts and osteocytes (pOC-ER alpha KO). Here our goal was to determine the effects of ER alpha and mechanical loading in skeletally-mature adult mice. We subjected 26-week-old skeletally-mature adult pOC-ER alpha KO and littermate control (LC) mice of both sexes to two weeks of in vivo cyclic tibial loading. ER alpha deletion in male mice did not alter bone mass or the response to loading. Adult female pOC-ER alpha KO mice had reduced cancellous and cortical bone mass and increased adaptation to high-magnitude mechanical loading compared to LC mice. Thus, ERa deletion from mature osteoblasts reduced the bone mass and increased the mechanoadaptation of adult female but not male mice. Additionally, compared to our previous work in young mice, adult female mice had greatly reduced mechanoadaptation and adult male mice retained most of their mechanoadaptation with age.

Automated summary

Estrogen receptor-alpha (ER alpha) plays a crucial role in skeletal maintenance and adaptation to mechanical loading, with its effects depending on sex and age. Deletion of ER alpha in mature osteoblasts leads to reduced bone mass and increased mechanoadaptation in adult female mice, while the effects in male mice are minimal.