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

Yarrow, Joshua F. PhD1,2; McCoy, Sean C. PhD1,2; Ferreira, J. Andries BS3; Pingel, Jennifer E. BS4; Conrad, Bryan P. PhD5; Wronski, Thomas J. PhD4; Williams, Alyssa A. BS4; Borst, Stephen E. PhD1,2; Brown, Marybeth PhD3

doi: 10.1097/gme.0b013e318255657f
Original Articles

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 (E2) 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 + E2, (4) OVX + 4 weeks of HLU, (5) OVX + E2 + HLU, (6) OVX + HLU + 2 weeks of quadrupedal REAMB, (7) OVX + E2 + HLU + REAMB, (8) OVX + HLU + REAMB + supplemental climbing, jumping, and balance exercises (EX), or (9) OVX + E2 + 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 E2, whereas BMD did not change in animals without E2. OVX reduced trabecular BMD at the femoral metaphysis, and HLU exacerbated this loss while also reducing cortical BMD. E2 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 E2, 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 E2, REAMB + EX did not negatively influence bone mineral characteristics.

Conclusions E2 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.

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From the 1VA Medical Center, Gainesville, FL; 2Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL; 3Department of Physical Therapy, University of Missouri-Columbia, Columbia, MO; and Departments of 4Physiological Sciences and 5Orthopedics and Rehabilitation, University of Florida, Gainesville, FL.

Received December 14, 2011; revised and accepted March 13, 2012.

Funding/support: This work was supported, in part, by Veterans Affairs grant CDA-2 (J.F.Y.), a Veterans Affairs Merit Award (S.E.B.), and National Aeronautics and Space Administration grants NA65-12300 and AG15796 (M.B.).

Financial disclosure/conflicts of interest: None reported.

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Address correspondence to: Joshua F. Yarrow, PhD, VA Medical Center, Research 151, Gainesville, FL 32607. E-mail:

©2012The North American Menopause Society