Global estrogen receptor-alpha knockout has differential effects on cortical and cancellous bone in aged male mice

Estrogen receptor-alpha knockout (ERKO) in female rodents results in bone loss associated with increased osteocyte sclerostin expression; whether this also occurs in males is unknown. Here, we examined the effects of ERKO on femoral cortical geometry, trabecular microarchitecture, and osteocyte sclerostin expression of the femur and lumbar vertebrae. At 14 months of age, male ERKO and wild-type (WT) littermates (n = 6 per group) were sacrificed, and femora and vertebra were collected. Cortical geometry and trabecular microarchitecture were assessed via micro-computed tomography; osteocyte sclerostin expression was assessed via immunohistochemistry. ANCOVA with body weight was used to compare ERKO and WT for cortical geometry; t-tests were used for all other outcomes. Regardless of skeletal site, ERKO mice had greater trabecular bone volume and trabecular number and decreased trabecular separation compared with WT. In the femoral diaphysis, ERKO had lower total area, cortical area, and cortical thickness compared with WT. The percentage of sclerostin+osteocytes was increased in ERKO animals in cortical bone but not in cancellous bone of the femur or the lumbar vertebrae. In conclusion, ERKO improved trabecular microarchitecture in aged male mice, but negatively altered femoral cortical geometry associated with a trend towards increased cortical sclerostin expression.