Researchers are still unsure of the accuracy of previous bone density measurements of their significance following a period of weightlessness. Rapid technological advances in the measurement of bone density will enable us now to measure bone density accurately at multiple sites in the skeleton with doses of radiation less than that given by a spine x ray. It may not be possible to obtain this type of information before the next series of space flights take place, although the bed-rest model may provide supporting information. Extensive testing of bone density on every astronaut should be performed before and after the space flight. Prevention and treatment can only be undertaken after gathering sufficient baseline information. The use of exercise in preventing bone loss is still highly speculative, but represents a relatively easy approach to the problem in terms of study

Gallagher, J. C.

English

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¢N91-I0581
Changes in Mineral Metabolism With Immobilization/Space Flight
J. c. Gallagher, M.D.
Creighton University
Omaha, Nebraska
introduction
What I would like to do is review briefly some
of the studies that have been done on the effect of
immobilization and weightlessness on bone. Only
limited information is available on bone loss in zero g
since relatively few subjects have experienced this
situation.
Much of the useful information comes from
the bed-rest model, which appears in many ways to be
similar to the weightlessness situation. There are a
number of interesting changes in mineral metabolism
that occur with weightlessness. Urine calcium
increases each week that the individual is immobilized
(refs. 1 to 6), as does fecal calcium. Consequently,
immobilized individuals develop severe negative
calcium balance. This disturbance in calcium
homeostasis has been shown to be associated with
marked bone loss from the skeleton (refs. 5 and 6).
Many years ago, it was shown that the immobilization
effect on mineral metabolism was minimized by
weight-bearing, but not by supine, exercises (ref. 7).
Similar metabolic findings to those seen in
immobilized patients were found in astronauts on the
84-day space flight (refs. 8 to 11). In some but not all
individuals, bone loss was regained. In some respects,
a parallel situation is seen in osteoporotic patients.
These patients often have severe malabsorption of
calcium, high urine calcium, and marked negative
calcium balance (ref. 12). Possibly, some of the
metabolic changes in these patients are due to partial
immobilization caused by chronic and severe
backache. Women at the time of the menopause also
have rapid bone loss associated with high urine
calcium levels but interestingly do not show any
obvious change in absorption of calcium. The most
obvious explanation for the changes that accompany
immobilization is that rapid bone resorption leads to
an elevated serum calcium, depression of parathyroid
hormone, reduced formation of 1,25-
dihydroxyvitamin D, malabsorption of calcium, and
negative calcium balance. It appears that the
metabolic changes associated with bone loss during
weightlessness are closer to the findings in
osteoporotic patients. What is interesting is why
women who have rapid bone loss at the time of the
menopause do not have malabsorption of calcium.
Perhaps other hormones, such as cortisone, which
affects absorption of calcium, may be contributors in
weightlessness or immobilization. It is not clear at this
moment whether the changes seen in vitamin D
metabolism and malabsorption of calcium are primary
or secondary phenomena subsequent to bone
resorption, and more work is needed in that area.
Bone Loss in Weightlessness
There is little information on changes in bone
itself during weightlessness. The results of one
experiment, performed on rats in a U.S.S.R. spacecraft,
showed a decrease in bone formation measured by
tetracycline labeling during space flight, and this type
of change in bone dynamics could contribute to bone
loss (ref. 13).
The earlier space flights showed that loss of
bone occurred in the radius and the os calcis (refs. 14
to 16). Further followup showed that the decrease in
bone mass was reversed in some but not all astronauts
(ref. 17). The last 5 years has seen the advent of new
techniques for measuring bone density which are
better than those used 10 years ago. These new
methods include dual photon absorptiometry and
computerized tomography. It has become clear from
recent experimental work in osteoporosis that one
cannot predict the rate of bone loss in one part of the
skeleton from changes in other parts. For example, in
osteoporotic patients, one sees normal radial density
in about one-third of patients but very low spine
density in all of them (ref. 18). Thus, I am not sure that
one can assume that significant losses of bone occur in
the femur or the spine during space flight even
though decreases in bone density have occurred in the
os calcis and the radius. Further prospective studies
are needed to establish this point. Future studies
should be planned to include measurement of density
53
https://ntrs.nasa.gov/search.jsp?R=19910001268 2020-03-19T20:28:40+00:00Z
at multiplesitesin theskeletonincludingthefemoral
neck,thespine,the oscalcis,andtheradiusaswellas
measurement of total-body calcium. These
measurements would give a more complete
understandingof skeletalchangesin immobilization.
Theuseof total-bodycalciumwould be especially
valuablesinceregionalchangesalsocanbemeasured
with thesametechnique.
Prevention or Treatment of Bone Loss
Other questions that need to be answered are
the effects of intervention therapy on immobilization.
A number of valuable experiments have examined the
effect of various therapeutic agents in bed-rest studies
(ref. 19). There are few data on the value of exercise
in preventing bone loss. This lack partly reflects the
fact that the technology for measuring different sites
of the skeleton has only been available during the last
2 to 3 years. A recent study showed a correlation
among spine density, femoral neck density, and
fitness as measured by maximum ventilatory oxygen
uptake (ref. 20) suggesting that fitness is a contributor
to bone density. Presumably, most astronauts are
extremely fit individuals who have probably
maximized their potential for increasing bone density.
Now that we have the ability to measure femoral neck
density, we can look at the effect of an exercise
program on the legs more carefully, since hip fracture
would be one of the more severe complications of
bone loss from the legs. Future experiments in space
which involve prolonged space flight should provide
answers to these questions. Also, since previous
results were not accurate enough, one should look
more closely at the recovery phase on bone since we
are not sure whether bone loss due to weightlessness
returns to normal. At the same time, bone density
measurements can be used to detect individuals with
low bone density, and I think it might be unwise to
have those individuals undergo weightlessness
repeatedly for several months if further studies show
decreases in spine and femur density.
If significant bone loss does occur in space
despite an exercise program, a strategy for preventing
bone loss may be pretreatment of astronauts with
agents such as the disphosphonates that significantly
retard bone turnover. This idea is speculative and
there are few animal data to support it, but work on
immobilized animals could easily test this hypothesis.
Conclusion
Vlte are still unsure of the accuracy of previous
bone density measurements or their significance
following a period of weightlessness. Rapid
technological advances in the measurement of bone
density will enable us now to measure bone density
accurately at multiple sites in the skeleton with doses
of radiation less than that given by a spine x-ray. It
may not be possible to obtain this type of information
before the next series of space flights take place,
although the bed-rest model may provide supporting
information. Extensive testing of bone density on
every astronaut should be performed before and after
the space flight. Prevention and treatment can only
be undertaken after gathering sufficient baseline
information. The use of exercise in preventing bone
loss is still highly speculative, but represents a
relatively easy approach to the problem in terms of
study.
,
.
.
4.
.
References
Deitrich, J. E.; Whedon, G. D.; and Shorr, E.:
Effects of Immobilization Upon Various
Metabolic and Physiologic Functions of
Normal Men. J. Clin. Invest., vol. 4, 1948, pp. 3-
36.
Whedon, G. D.; and Shorr, E.: Metabolic
Studies in Paralytic Acute Anterior
Poliomyelitis. II. Alterations in Calcium and
Phosphorus Metabolism. J. Clin. Invest., vol.
36, 1957, pp. 966-981.
Donaldson, C. L.; Hulley, S. B.; et al.: Effect of
Prolonged Bed Rest on Bone Mineral.
Metabolism, vol. 19, 1970, pp. 1071-1084.
Hulley, S. B., Vogel, J. M.; et al.: The Effect of
Supplemental Oral Phosphate on the Bone
Mineral Changes During Prolonged Bed Rest.
J. Clin. Invest., vol. 50, 1971, pp. 2506-2518.
Hansson, T. H.; Roos, B. O.; and Nachemson,
A.: Development of Osteopenia in the Fourth
Lumbar Vertebra During Prolonged Bed Rest
After Operation of Scoliosis. Acta Orthop.
Scandinavia, vol. 46, 1975, pp. 621-630.
54
w __
I
.
.
.
.
10.
11.
12.
13.
14.
Krolner, B.; and Toft, B." Vertebral Bone Loss:
An Unheeded Side Effect of Therapeutic Bed
Rest. Clin. Sci., vol. 64, 1983, pp. 537-540.
Issekutz, B.; Blizzard, J. J.; Birkhead, N. C.; and
Rodahl, K.: Effect of Prolonged Bed Rest on
Urinary Calcium Output. J. Appl. Physiol., vol.
32, 1966, pp. 1013-1020.
Whedon, G. D.; Lutwak, L.; et al." Mineral and
Nitrogen Metabolic Studies on Skylab Orbital
C_ r,-i_ _ l_ ,
atad_ r,,gn_s. Trans. Assoc. American
Physicians, vol. 87, 1974, pp. 95-110.
Leach, C. S.; and Rambaut, P. C.: Biochemical
Observations of Long Duration Manned
Orbital Spaceflight. J. American Med.
Women's Assoc., vol. 30, no. 4, 1975, pp. 153-
172.
Rambaut, P. C.; Leach, C. S.; and Whedon, G.
D.: A Study of Metabolic Balance in
Crewmembers of Skylab IV. Acta Astronaut.,
vol. 6, no. 10, 1979, pp. 1313-1322.
Rambaut, P. C.; and Johnston, R. S.:
Prolonged Weightlessness and Calcium Loss in
Man. Acta Astronaut., vol. 6, no. 9, 1979,
pp. 1113-1122.
Gallagher, J. C.; Riggs, B. L.; et al.: Intestinal
Calcium Absorption and Serum Vitamin D
Metabolites in Normal Subjects and
Osteoporotic Patients. J. Clin. Invest., vol. 64,
no. 3, Sept. 1979, pp. 729-736.
Morey, E. R.; and Baylink, D. J.: Inhibition of
Bone Formation During Space Flight. Science,
vol. 201, Sept. 1978, pp. 1138-1141.
Mack, P. B.; and Vogt, F. B.:
Roentgenographic Bone Density Changes in
Astronauts During Representative Apollo
15.
16.
17.
18.
19.
20.
Space Flight. American J. Roentgen. Radium
Therapy Nucl. Med., vol. 113, 1971, pp. 621-
623.
Vogel, J. M.; and Whittle, M. W.: Bone
Mineral Changes: The Second Manned Skylab
Mission. Aviation, Space & Environ. Med., vol.
47, 1976, pp. 396-400.
Stupakov, G. P.; Kazeykin, V. S., Kozlovskiy,
A. P.; and Korolev, V. V.: Evaluation of
Changes in Human Axial Skeletal Bone
Structures During Long-Term Spaceflights.
Kosm. Biol. Aviakosm. Med., vol. 18, no. 2,
Mar.-Apr. 1984, pp. 33-37.
Tilton, R. E.; Degioanni, J. J. C; and Schneider,
V.S.: Long-Term Follow-Up of Skylab Bone
Demineralization. Aviation, Space & Environ.
Med., vol. 51, 1980, pp. 1209-1213.
Riggs, B. L., Wahner, H. W., et al.: Differential
Changes in Bone Mineral Density of the
Appendicular and Axial Skeleton With Aging.
J. Clin. Invest., vol. 67, no. 2, Feb. 1981, pp.
328-335.
Schneider, V. S.; and McDonald, J.: Skeletal
Calcium Homeostasis and Countermeasures To
Prevent Disuse Osteoporosis. Calcif. Tissue
Int., vol. 36, suppl. 1, 1984, pp. $151-$154.
Pocock, N. A.; Eisman, J. A.; et al.: Physical
Fitness Is a Major Determinant of Femoral
Neck and Lumbar Spine Bone Mineral Density.
J. Clin. Invest., vol. 78, no. 3, Sept. 1986, pp.
618-621.
55


Changes in mineral metabolism with immobilization/space flight

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