Variation in estradiol level affects cortical bone growth in response to mechanical loading in sheep

Although mechanical loading can stimulate cortical bone growth, little is known about how individual physiology affects this response. This study demonstrates that in vivo variation in estradiol (E2) level alters osteoblast sensitivity to exercise-induced strains, affecting cortical bone responses to mechanical loading. Subadult sheep were divided into treatment groups that varied in terms of circulating E2 levels and loading (exercised and sedentary). After 45 days, periosteal cortical bone growth rates and cross-sectional properties were measured at the midshafts of hindlimb bones and compared with strain data. The results indicate significant interactions between E2 and strain. Cortical bone growth in exercised animals with elevated E2 levels was 27% greater in the femur, 6% greater in the tibia, and 14% greater in the metatarsal than in exercised animals with lower E2 levels, or sedentary animals regardless of E2 dose (P<0.05). There was also a trend toward greater resistance to deformation in the tibia, but not the metatarsal, in the exercised, high-E2 group compared to the other treatment groups. These results demonstrate that E2 plays a role in mediating skeletal responses to strain, such that physiological variation in E2 levels among individuals may lead to differential growth responses to similar mechanical loading regimes. Efforts to model the relationship between environmental strain and bone morphology should include the effects of physiological variation in hormone levels.