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Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905
Address all correspondence and requests for reprints to: Russell Turner, Ph.D., 3–69 Medical Science Building, Mayo Clinic, Rochester, Minnesota 55905.
A 14-day orbital spaceflight was performed using ovariectomized Fisher
344 rats to determine the combined effects of estrogen deficiency and
near weightlessness on tibia radial bone growth and cancellous bone
turnover. Twelve ovariectomized rats with established cancellous
osteopenia were flown aboard the space shuttle Columbia (STS-62).
Thirty ovariectomized rats were housed on earth as ground controls: 12
in animal enclosure modules, 12 in vivarium cages, and 6 killed the day
of launch for baseline measurements. An additional 18 ovary-intact rats
were housed in vivarium cages as ground controls: 8 rats were killed as
baseline controls and the remaining 10 rats were killed 14 days later.
Ovariectomy increased periosteal bone formation at the tibia-fibula
synostosis; cancellous bone resorption and formation in the secondary
spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA)
levels for the prepro-
2(1) subunit of type 1 collagen, osteocalcin,
transforming growth factor-ß, and insulin-like growth factor I in the
contralateral proximal tibial metaphysis and for the collagen subunit
in periosteum pooled from tibiae and femora and decreased cancellous
bone area. Compared to ovariectomized weight-bearing rats, the flight
group experienced decreases in periosteal bone formation, collagen
subunit mRNA levels, and cancellous bone area. The flight rats had a
small decrease in the cancellous mineral apposition rate, but no change
in the calculated bone formation rate. Also, spaceflight had no effect
on cancellous osteoblast and osteoclast perimeters or on mRNA levels
for bone matrix proteins and signaling peptides. On the other hand,
spaceflight resulted in an increase in bone resorption, as ascertained
from the diminished retention of a preflight fluorochrome label. This
latter finding suggests that osteoclast activity was increased. In a
follow-up ground-based experiment, unilateral sciatic neurotomy of
ovariectomized rats resulted in cancellous bone loss in the unloaded
limb in excess of that induced by gonadal hormone deficiency. This
additional bone loss was arrested by estrogen replacement. We conclude
from these studies that estrogen alters the expression of signaling
peptides believed to mediate skeletal adaptation to changes in
mechanical usage and likewise modifies the skeletal response to
mechanical unloading.
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G. L. Evans, E. Morey-Holton, and R. T. Turner Spaceflight has compartment- and gene-specific effects on mRNA levels for bone matrix proteins in rat femur J Appl Physiol, June 1, 1998; 84(6): 2132 - 2137. [Abstract] [Full Text] [PDF]
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