NASA Human Research Program Investigators' Workshop (2012)
4105.pdf
EFFECTS OF SPACEFLIGHT ON BONE MINERAL DENSITY AND MICROARCHITECTURE IN
MICE: RESULTS FROM STS-135
R. Ellman1,4, V. L. Ferguson2, E. W. Livingston3, M. Lemus3, L. D. Louis4, J. M. Spatz1,4, L. S. Stodieck5, M. L.
Bouxsein4, T. A. Bateman3
1
Division of Health Sciences & Technology, Harvard-MIT; 2Dept of Mechanical Engineering, Univ of Colorado;
3
Dept of Biomedical Engineering, Univ of North Carolina - Chapel Hill; 4Dept of Orthopedic Surgery, Beth Israel
Deaconess Medical Center and Harvard Medical School; 5BioServe Space Technologies, Univ of Colorado
BMD (% change)
INTRODUCTION
Mice are commonly used in ground-based studies to examine the effects of microgravity on the skeletal system, yet
there are few reports describing the skeletal changes resulting from spaceflight. Thus, we aimed to describe the
skeletal changes in young adult mice following exposure to microgravity.
METHODS
Female, 9-week old C57BL/6C mice were assigned to one of four groups (n=15 each): Flight-Vehicle, FlightTreated, Ground-Vehicle, and Ground-Treated. Animals in the treatment groups received sclerostin antibody
(Amgen, Thousand Oaks, CA) to stimulate bone formation, and are not included in this abstract. Mice were
acclimated to wire cage floors and NASA food bars for two weeks prior to the flight. One day before flight, mice
were injected subcutaneously with vehicle or drug. Flight groups were housed in animal enclosure modules (AEM,
NASA Ames) that flew on STS-135 for a mission duration of 12 days and 18.5 hours. Ground controls were housed
in identical AEM’s within an orbital environment simulator (OES) at NASA Kennedy Space Center to mimic the
temperature, humidity, and CO2 of the space shuttle middeck. Bone mineral density (BMD, g/cm2) of the total body,
lumbar spine and hindlimb were measured in vivo three days before launch and immediately after landing using
dual-energy X-ray absorptiometry. Tibiae, femora and L5 vertebrae were harvested at disposition for ex vivo
assessment of trabecular and cortical bone microarchitecture using µCT.
Ground
12
RESULTS
*
Flight
At baseline, body mass and BMD were equal in Flight-Vehicle (“Flight”)
10
and Ground-Vehicle (“Ground”) groups. Body mass declined similarly in
*
8
Flight and Ground groups (-1.6 ± 1.7 g and -1.3 ± 0.8 g, respectively;
6
p<0.005 vs. preflight for both). Total body BMD (TBBMD) increased in
the Ground group by 7.2 ± 3.8% (p < 0.05 vs. preflight) as the growing
4
*
young adult animals acquired bone mass. This bone acquisition was
2
diminished with spaceflight, as the Flight group gained 2.2 ± 2.4%
0
TBBMD (p<0.0005 vs. Ground). Similar changes in BMD were seen in the
Total Body Hindlimb Spine
hindlimb, but not at the spine (Figure). At the proximal tibia, distal femur
Longitudinal
changes in bone mineral
and L5 vertebra, trabecular BV/TV and trabecular thickness (Tb.Th) were
markedly decreased (p<0.0001) in Flight relative to Ground, with greater density. *p < 0.05 vs. preflight; bars =
p<0.05 for Flight vs. Ground
differences observed in the hindlimb than in the axial skeleton. Trabecular
number did not differ in any of the regions. Mid-tibia cortical thickness (Ct.Th) and cortical area fraction (BA/TA)
were also lower in Flight vs. Ground, but differences were less than those seen in trabecular bone (Table).
µCT Measurements of trabecular and cortical bone microarchitecture. (mean ± st dev), * p < 0.05 for Flight vs. Ground
Trabecular
Cortical
Proximal Tibia
Distal Femur
L5 vertebra
Midshaft Tibia
BV/TV
Tb.Th
BV/TV
Tb.Th
BV/TV
Tb. Th
Ct.Th
BA/TA
(%)
(μm)
(%)
(μm)
(%)
(μm)
(μm)
(%)
Ground
10.0±2.1
46.6±5.6
5.2±1.0
38.8±3.8
18.4±3.3
44.1±5.8
193±9
61.7±2.5
0.111±0.012
Flight
5.4±0.9
36.1±2.4
3.0±0.7
28.7±2.1
13.9±1.8
36.9±1.7
183±6
59.2±1.8
0.109±0.009
Diff (%)
-46.0*
-22.5*
-42.7*
-26.2*
-24.3*
-16.4*
-5.2*
-4.1*
-1.8
pMOI (mm4)
CONCLUSION
Bone mineral density and trabecular architecture were significantly reduced in mice exposed to ≈13 days of
spaceflight as compared to ground controls, with deterioration in the hindlimb exceeding that of the spine. Cortical
bone was also reduced, but to a lesser extent than trabecular bone. This site and compartment specificity of bone loss
is consistent with patterns of bone loss observed in astronauts by 3D QCT data of the hip and spine.
ACKNOWLEDGEMENTS: We acknowledge funding support from the NASA ISS National Lab, NASA FSB,
NSBRI, NASA HRP and Amgen. This study is presented on behalf of the STS-135 Musculoskeletal Research Team.