Oral Estradiol Impact On Mitigating Unloading-Induced Bone Loss In Ovary-Intact Rats

BACKGROUND: The impact of the spaceflight environment on endogenous estrogen production in female crewmembers and the resulting impact on other adaptations, like bone loss, is an under-investigated topic. Hence, we investigated the interaction of exogenous 17-beta estradiol (E2) treatment and disuse to test the hypothesis that E2 treatment would mitigate disuse-induced bone loss.METHODS: There were 40 virgin female Sprague-Dawley rats (5 mo old) randomized to placebo (PL; 0 ppm E2) or estrogen (E2; 10 ppm E2) treatments, delivered via custom-made rodent diets; half of each group was randomized to either weightbearing (WB) or hindlimb unloading (HU) for similar to 39 d.RESULTS: We observed expected lower values after HU (6-15%) in volumetric BMD and cross-sectional areas at the proximal tibia metaphysis (PTM, by pQCT), 20% lower %BV/TV (nonsignificant) at the PTM, and 11% lower femoral neck maximal load; none of these HU-induced impacts were modified by E2. Impaired PTM periosteal expansion was observed in all E2-treated rats, with smaller (-13 to -18%) cross-sectional areas. Midshaft tibial geometry was unaffected by E2 treatment, but large reductions (-73 to -81%) in periosteal bone formation indices were observed in E2-treated rats.DISCUSSION: In summary, modest supplementation of exogenous E2 did not mitigate decrements in volumetric BMD, PTM cross-sectional geometry, or femoral neck strength observed with HU. However, numerous independent impacts of E2 treatment were observed, with significant suppression of periosteal bone formation indices. If maintained over time, this might impact negatively on cortical bone integrity during prolonged nonweightbearing.