| Osteoporosis in spaceflight | ||
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Spaceflight
increases risk of bone loss: The continuous and progressive loss of
calcium and weight bearing bone noted in space flight crews is one of
the most serious impediments to long duration manned space flight.
Skeletal changes and loss of total body calcium have been noted
in both humans and animals exposed to microgravity from 7 to 237 days.
During the Apollo and Skylab missions, photon absorptiometry was
used to assess pre- and post-flight bone mineral mass.
For the 12 crew members of Gemini 4, 5, and 7, and Apollo 7 and
8, the average post-flight loss from the os calcis (heel) was 3.2
percent over an average of 8.5 days (1-3)
. Analysis of
in-flight urine, fecal, and plasma samples from Skylab missions revealed
changes in urinary output of hydroxy-proline indicating degradation of
the collagenous matrix substance of weight bearing bones. Nitrogen output also increased with a resultant muscle
atrophy occurring. Elevated
concentrations of urinary calcium were noted in Skylab astronauts
starting within the first days of flight; in many of the astronauts
urinary calcium concentrations remained at elevated levels throughout
the mission. A
direct effect of microgravity is the loss of mechanical stress on the
skeletal system. Although
in-flight exercise is a helpful countermeasure used by astronauts, the
greatest losses in the US flight program occurred in the 84-day Skylab 4
mission even though exercise was regularly performed.
Crew members using exercise as a countermeasure still lost an
average of 4 percent of bone over the 84 day mission period (4)
. In the 237-day
Soviet Soyuz T-10 mission, the Cosmonauts lost bone in spite of 2-4
hours of daily exercise. Both
compact and trabecular bone was lost from the os calcis during this
mission. Bone loss appears
to increase in general proportion to mission length, from 4 percent to
19.8 percent over an 84 to 184 day period (4,
13)
. The bone loss suffered in flight is
not fully recovered after return to gravity, which will be a problem on
long term missions. Paradoxically,
excessive exercise may be part of the problem; Stein et al have reported
a negative energy balance in some of the longer term missions
strongly suggesting the need for a more efficient exercise
programs that would not result in a negative energy balance. The
loss of bone in the presence of consistent exercise suggests additional
molecular mechanisms in spaceflight bone loss.
Various lines of evidence from human and animal studies suggest that
bone loss in space flight is due to a decrease in bone formation.
Rat studies aboard Spacelab 3 and animal studies flown on the
Cosmos Biosatellites provided evidence for significant skeletal changes
including bone mineral content, even on flights of short duration. It is
probable that the decrease in bone formation is caused by the direct
lack of gravity in microgravity. Previous
studies performed by this laboratory have shown that there is a direct
gravitational effect on osteoblasts, which alters the extracellular
matrix, nuclear morphology and gene expression.
First, on STS-56 we demonstrated a change in cell and nuclear
shape with slowing of osteoblast growth after 4 days of spaceflight,
even though glucose metabolism per cell was unchanged (18)
.
More recently, we have demonstrated that gene expression,
cytoskeleton and nuclear structure is changed when compared to ground
controls and to on board 1-g controls. The
consequences of bone loss in space are: Taken
together, these data predict that bone loss has serious implications for
long-term inhabitants of the space station and for future long-term
space exploration, e.g., a Mars Mission. Current countermeasures to bone loss in space flight:
To date, all countermeasures used to stop bone demineralization
during spaceflight or bed-rest have had limited success.
Exercise, dietary supplementation with calcium or phosphorous,
and pharmacological treatment with salmon calcitonin and diphosphonates
have been tried either in flight or in bed-rest studies.
The most promising countermeasures are exercise and diphosphonate
treatment. However,
exercise is only effective in bed-rest studies when there is at least 4
hours of activity. The older diphosphonates have side effects which
include a potential for causing tumors (8)
. The newer
diphosphonate compounds show promise and may be useful in future
flights, however, they do not stimulate new osteoblast growth and their
action merely slows the remodeling breakdown by the osteoclast.
Moreover, there is currently little information on bone quality
after long term use of diphosphonates. Here on earth it has been
demonstrated that bone growth is supported by hormone replacement
therapy (HRT) (33)
and by stress exercise. (10-12)
. Normal exercise
can result in forces from 1.5xg to 12xg, however, we found no studies
that defined the absolute time and duration of gravity force that is
required to stimulate bone gene expression and growth. Literature Cited
1. Nicogossian
AE, H. C. a. P. S. (1989) Space
Physiology and Medicine, Lea and Febiger, Philadephia |