A rehabilitation exercise program induces severe bone mineral deficits in estrogen-deficient rats after extended disuse

Objective: Both estrogen and mechanical loading regulate bone maintenance. However, mechanical overload seems less effective in enhancing bone mineral density (BMD) in estrogen-deficient women. The aim of this study was to determine whether estradiol (E-2) influences early-phase bone adaptations to reambulation (REAMB) and/or rehabilitation exercises after hindlimb unloading (HLU) of ovariectomized rats. Methods: Eighty-one 5-month-old female Sprague-Dawley rats were randomized into the following groups: (1) intact controls, (2) ovariectomy (OVX), (3) OVX + E-2, (4) OVX + 4 weeks of HLU, (5) OVX + E-2 + HLU, (6) OVX + HLU + 2 weeks of quadrupedal REAMB, (7) OVX + E-2 + HLU + REAMB, (8) OVX + HLU + REAMB + supplemental climbing, jumping, and balance exercises (EX), or (9) OVX + E-2 + HLU + REAMB + EX. Serial dual-energy x-ray absorptiometry scans were performed to track total body bone characteristics throughout the study, and peripheral quantitative computerized tomography was used to determine distal femoral metaphyseal bone mineral characteristics. Results: Total body BMD increased by 4% to 8% in all animals receiving supplemental E-2, whereas BMD did not change in animals without E-2. OVX reduced trabecular BMD at the femoral metaphysis, and HLU exacerbated this loss while also reducing cortical BMD. E-2 protected against OVX + HLU-induced bone loss at the femoral metaphysis. Conversely, REAMB did not alter BMD, regardless of estrogen status. In the absence of E-2, REAMB + EX resulted in severe bone loss after OVX + HLU, with trabecular BMD and cortical BMD measurements that were 91% and 7% below those of controls, respectively (P <= 0.001). However, in the presence of E-2, REAMB + EX did not negatively influence bone mineral characteristics. Conclusions: E-2 protects against bone loss resulting from combined OVX + HLU of rodents. In the absence of estrogen, exercise induces disadvantageous early-phase bone adaptations after extended disuse.