Skeletal effects of estrogen and mechanical loading are structurally distinct

Estrogen has been suggested to influence skeletal homeostasis by both increasing the sensitivity of the feedback control system for skeletal rigidity and acting directly on bone surfaces. The objective of the present study was to explore the proposed interaction between the skeletal effects of estrogen and locomotion. Thirty 3-week-old littermates of female Sprague–Dawley rats were first randomly assigned into bilateral sham (E+) or ovariectomy (E−) surgery after which, the left hindlimb each study animal was cast immobilized (L−) while the right limb served as locomotively loaded control (L+), a classic 2 × 2 factorial study design. After 8-week study period, femoral neck, femur midshaft and distal metaphysis were analyzed by peripheral quantitative computed tomography (pQCT), microcomputed tomography (µCT), and mechanical testing. The loading-induced effects were virtually identical in the estrogen-replete (E+) and estrogen-deplete (E−) groups (Femoral neck: + 78% vs. + 69% in the tCSA, + 74% vs. + 55% in the tBMC, − 6.0% vs. − 7.2% in the tBMD, and + 33% vs. + 58% in the Fmax; Femoral midshaft: + 6.9% vs. + 3.9% in the cCSA, + 13% vs. + 13% in the tCSA, + 23% vs. + 16% in the cBMC, + 5.2% vs. + 5.1% in the cBMD, and + 8.0% vs. + 8.0% in the Fmax, respectively. All comparisons, NS), challenging the alleged modulatory effect of estrogen on skeletal mechanosensitivity. Estrogen did not have an independent effect on the periosteal apposition at any of the evaluated bone regions. Instead, according to its primary reproductive function, the effects of estrogen were restricted to accrual of bone mass only, the stimulus being apparent at the endosteal surface of cortex and trabecular structure of the distal metaphysis. In conclusion, the present results indicate that that the actions of estrogen and loading on bone structure are independent and additive in nature.