The skeletal responsiveness to mechanical loading is enhanced in mice with a null mutation in estrogen receptor-β

Mechanical loading caused by physical activity can stimulate bone formation and strengthen the skeleton. Estrogen receptors (ERs) play some role in the signaling cascade that is initiated in bone cells after a mechanical load is applied. We hypothesized that one of the ERs, ER-β, influences the responsiveness of bone to mechanical loads. To test our hypothesis, 16-wk-old male and female mice with null mutations in ER-β (ER-β^-/-) had their right forelimbs subjected to short daily loading bouts. The loading technique used has been shown to increase bone formation in the ulna. Each loading bout consisted of 60 compressive loads within 30 s applied daily for 3 consecutive days. Bone formation was measured by first giving standard fluorochrome bone labels 1 and 6 days after loading and using quantitative histomorphometry to assess bone sections from the midshaft of the ulna. The left nonloaded ulna served as an internal control for the effects of loading. Mechanical loading increased bone formation rate at the periosteal bone surface of the mid-ulna in both ER-β^-/- and wild-type (WT) mice. The ulnar responsiveness to loading was similar in male ER-β^-/- vs. WT mice, but for female mice bone formation was stimulated more effectively in ER-β^-/- mice (P < 0.001). We conclude that estrogen signaling through ER-β suppresses the mechanical loading response on the periosteal surface of long bones.