18th IAA Humans in Space Symposium (2011)
2370.pdf
Earth-Based Applications of Space Radiation-Induced Bone Loss
T. A. Bateman1, R. D. Carpenter2, T. F. Lang2, M. V. Lawrence1, J. S., Willey3, V. Sehgal4, N. S. Ramsinghani4, J.
V. Kuo4, M. Al-Ghazi4, J. H. Keyak5
1
Departments of Biomedical Engineering and Radiation Oncology, University of North Carolina, Chapel Hill, NC
(bateman@unc.edu), 2Department of Radiology and Biomedical Imaging, University of California, San Francisco,
CA, 3Departments of Radiation Oncology and Rheumatology, Wake Forest University, Winston-Salem, NC,
4
Department of Radiation Oncology and 5Department of Radiological Sciences, University of California, Irvine, CA,
(jhkeyak@uci.edu)
RADIATION THERAPY-INDUCED OSTEOPOROSIS
We have identified a rapid bone loss in mice from exposure to spaceflight-relevant doses and types of ionizing
radiation (0.5-1.0 Gy of protons and heavy ions). Because cancer patients receive localized doses of radiation that
are considerably higher, we designed a study to examine if this phenomenon was applicable to the clinical setting.
% Change aBMD
% Change BMC
% Change Load
% Change vBMD
Purpose/Objective
Postmenopausal women receiving radiation therapy (RT) for pelvic tumors have a 65-200% increased risk of hip
fracture. Mortality statistics are poor after a hip fracture, with nearly 20% not surviving a year. It is generally
accepted that RT damages bone-forming
osteoblasts resulting in a gradual loss of bone.
A
B
Fall Load
Stance Load
Integral
Trabecular Cortical
However, we have observed in rodent models
0.0
0
0.0%
that radiation activates bone-resorbing
-2.5
osteoclasts resulting in rapid loss of bone. To
-5.0
-5.9%
-10
test the clinical application of this new cellular
-7.5
*
-4.8%
*
mechanism, bone density and mineral content
-10.0
-16.5%
-9.5%
-20
-12.5
*
were examined in women receiving RT for
*
-15.0
gynecological tumors.
Neck
Trochanter
C 0 Integral Trabecular Cortical D 0.0 Integral
Material/Methods
-5
-2.5
-10
8 women provided informed. CT scans were
-15
-5.0
performed pre-RT and on the last day of RT at
-20
-15.5%
-14.0%
-7.5
UCI. Patients received 50.4 Gy over the course
-25
-5.4%
*
*
-30
of 28 fractions. Total dose to the proximal femur
-10.0
-7.1%
*
*
-23.7%
-8.2%
-35
*
was ~25.0 Gy. CT scans were used for FE
*
-12.5
-40
strength and vQCT analyses. Proximal femur
Figure 1. Effect of RT-induced bone mass declines in six-weeks
strength was calculated for fall and single-limb
for A) fall and stance strength (load), B) proximal femur vBMD
stance loads. Volumetric bone mineral density
for trabecular, cortical and integral (trabecular + cortical)
(vBMD) and bone mineral content (BMC) were
compartments, C) proximal femur BMC, and D) DXA equivalent
calculated via vQCT for the spongy trabecular
aBMD for whole femur, neck and trochanter. * p < 0.05
(Tr), dense cortical (Co) and integral (Tr + Co)
compartments of the proximal femur. Significance was determined by paired t-test.
Results and Conclusion
Figure 1 shows RT caused rapid decline of bone strength, density and mineral content in the proximal femur. Only
an early activation of bone resorbing osteoclasts can account for this rate of loss (BMC decline >2%/wk). For
context, the bone loss from 6-wks of RT is roughly equivalent to 2-3 years of bone loss in women due to
menopause.
Research support from Procter and Gamble Pharmaceuticals and NSBRI through NASA NCC 9-58-264.