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Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical PropertiesSpace flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with ZOL not modulating trabecular thickness in CL + NAHU mice. In summary, our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. Based on these results, we conclude that, at the structural and stiffness level, zoledronate treatment during simulated spaceflight does not impede the skeletal response to axial compression. In contrast to our hypothesis, our data show that zoledronate confers no additional mechanical or structural benefit beyond those gained from cyclical loading.
Document ID
Acquisition Source
Ames Research Center
Document Type
Conference Paper
Scott, R. T.
(San Jose State Univ. San Jose, CA, United States)
Nalavadi, M. O.
(Blue Marble Space Seattle, WA, United States)
Shirazi-Fard, Y.
(Wyle Labs., Inc. Moffett Field, CA, United States)
Castillo, A. B.
(City Univ. of New York Brooklyn, NY, United States)
Alwood, J. S.
(NASA Ames Research Center Moffett Field, CA United States)
Date Acquired
February 9, 2016
Publication Date
February 8, 2016
Subject Category
Aerospace Medicine
Report/Patent Number
Meeting Information
Meeting: 2016 Human Research Program Investigators'' Workshop
Location: Galveston, TX
Country: United States
Start Date: February 8, 2016
End Date: February 11, 2016
Sponsors: NASA Headquarters
Funding Number(s)
Distribution Limits
Public Use Permitted.
Mechanical Loading
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