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Above: STS-96 Crew members floating through a mission.
From left: astronauts Tamara Jernigan and Julie Payette of the Canadian Space
Agency (CSA), and Russian cosmonaut Valery Tokarev.
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Above: Researchers at NASA Ames Research Center use
a myriad of sensors, like this shoe insole to monitor the mechanical forces on
bones.
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Above: Using vibrations, the MRTA assesses bone strength.
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Weak in the Knees - The Quest for a Cure
The most common disease affecting bones, osteoporosis - literally meaning
porous bones - results in the loss of bone mass, rendering bones brittle and
more susceptible to fractures. Though it afflicts both men and women, it is a
problem that plagues more women than men. It also affects women more severely
than men, especially after menopause.
Exposure to the microgravity environment of space causes astronauts to lose
calcium from bones. This loss occurs because the absence of Earth's gravity disrupts
the process of bone maintenance in its major function of supporting body weight.
Space biomedical researchers have found that exposure to the microgravity environment
of space causes men and women of all ages to lose up to 1% of their bone mass
per month due to disuse atrophy, a condition similar to osteoporosis. It is not
yet clear whether losses in bone mass will continue as long as a person remains
in the microgravity environment or level off in time.
The mystery, for the moment, is what signals permit bone tissue to adapt to
a weightless or an Earth (1 g) environment. Researchers do not yet know whether
the biomechanical stimuli that are changed by microgravity directly affect osteoblast
and osteoclast function or if other physiological factors such as hormone levels
or poor nutrition contribute to bone loss. NASA investigators are studying gravity-sensing
systems in individual bone cells by flying cultures of these cells on the Space
Shuttle and observing how they function.
Osteoporosis: A Silent Killer
According to the National Osteoporosis
Foundation, 28 million Americans suffer from osteoporosis - 80% of them are
women. The disease is responsible for 1.5 million fractures annually, costing
approximately $14 billion a year and those numbers are growing. Of the women
who suffer an osteoporotic hip fracture, one in five will die within the first
year following the fracture. Half the women who do survive never fully recover
and require long term nursing home care, according to the Journal of the American
Medical Association. The Task Force for Aging Research Funding has projected
that the cost of dealing with osteoporosis could rise to $30 billion - $60 billion
a year by 2020 without new preventive measures and treatments.
Men and women both lose bone mass due to aging, starting around age 30. Women
start with 10 to 25 percent less total bone mass than men do at maturity, though
mainly because the average woman's skeleton generally has less weight to support
than the average man's. Following menopause, a woman's bone mass loss accelerates
dramatically. Once her body stops producing the female sex hormone, estrogen,
a woman can lose up to 3% of her bone mass annually in the absence of hormone
replacement therapy, but even hormone replacement is not a totally effective
remedy.
In comparison, Earthbound osteoporosis due to estrogen deficiency affects bones
in a more diffuse way. The type of bone loss that occurs during space flight
appears to be somewhat akin to the acute disuse osteoporosis that afflicts patients
immobilized by spinal cord injuries on Earth, though is not a perfect model for
explaining how microgravity affects bone. Unlike spinal-cord injury patients
whose bodies are damaged and suffering bone deterioration in a gravitational
environment, space flight crewmembers are healthy individuals adapting to environmental
decreases in weight bearing (bio-mechanical loading).
The Bare Bone Facts
Exercise creates forces that stimulate bone development.
Bones are composite structures, made up of bone matrix (the framework of bone,
as it were) and mineral deposits that fill out the matrix (the plaster, so to
speak). Bone structure is the product of three processes - longitudinal growth,
modeling, and remodeling - each following a complex sequence of steps. Alteration
of any step may yield a similar kind of change in bone, though different mechanisms
may be responsible.
Normally, the breakdown of old bone mass (resorption) and the formation of
new bone mass (growth) occur constantly, in a balanced cycle called remodeling.
Bone cells called osteoblasts make new bone, and cells called osteoclasts break
down old bone mass. In the weight-bearing parts of the skeleton, exposure to
microgravity depresses the activity of bone-forming cells (osteoblasts) and may
or may not stimulate bone-resorbing cells (osteoclasts). The remodeling process
becomes unbalanced and the result is a localized loss of bone mass. Research
also has shown that calcium is distributed differently throughout the skeleton
in microgravity and in Earth-based spaceflight models such as bed rest.
Changes in bones and muscles due to inactivity on Earth causes similar results
to those experienced in space flight. Reduced physical activity is characteristic
of aging and could well be a factor in the loss of bone, but researchers have
not yet determined how much of a role disuse plays on Earth. The connection is
poorly documented in large part because researchers have not yet developed good
systems for quantifying daily activity (or stress-loading) levels.
Researchers believe the mechanism of bone mass loss is different in astronauts,
post-menopausal women, aging men, and immobilized individuals. Though scientists
have some ideas about how and why osteoporosis of various types occurs, they
do not yet know precisely what causes these different conditions.
NASA Life Sciences Division's Role
The role of NASA's Space Life Sciences Division, formerly Life and Biomedical
Sciences and Applications, is to acquire the knowledge needed to ensure that
space flight crew members remain healthy and productive during and after flight.
One area of research is the loss of muscle and bone mass in astronauts during
space flight, called disuse atrophy. Currently, the Life Sciences' Space Biomedical
program is focused on ensuring that losses of bone mass in space flight do not
put space crew members at risk of injury during long-duration missions or upon
return to Earth. The knowledge and technologies gained through their research
to help astronauts in long space flights could help those on Earth suffering
from osteoporosis and related bone diseases.
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Above: Bones suffering from osteoporosis (right) have
a less dense structure compared to normal bone (left). Reproduced from J Bone
Miner Res 1986; 1:15-21 with permission of the American Society for Bone and
Mineral Research.
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Above: Most fractures occur at the stress points of
the body like the spine and hip. Reproduced from National Osteoporosis Foundation
Web site.
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Discoveries made in the course of space biomedical research on bone are already
contributing to a better understanding of osteoporosis and the treatment of bone
mass loss on Earth as well as in space. The single most important contribution
that NASA research has made to the understanding of bone deterioration in osteoporosis
is heightened awareness of the importance of gravity, activity, and biomechanics
- that is, the mechanical basis of biological activity - in bone remodeling.
Mechanical forces - the action of energy on matter - appear to coordinate bone
shaping processes. The standard theory of bone remodeling states the body translates
mechanical force into biochemical signals that drive the basic processes of bone
formation and resorption. Aging, especially in post-menopausal women, and exposure
to microgravity uncouple bone resorption and formation. When this uncoupling
occurs, formation lags behind resorption, and the result is bone loss.
Researchers are not yet certain whether bone resorption speeds up or the bone
formation slows down, though recent experimentation in space indicates that microgravity
might somehow affect both processes. Progress in developing methods of preventing
or treating disuse atrophy and osteoporosis depends on better understanding the
mechanisms that cause the problem. Determining how the body translates mechanical
loading (physical stress or force) into the signals that control bone structure
may reveal how aging, inactivity, and space flight uncouple bone formation and
resorption. Only in the absence of gravity can we determine the influence of
weight and stress on bone dynamics.
By studying what mechanisms translates mechanical stress on bones into biochemical
signals that stimulate bone formation and resorption, space life scientists may
be able to determine how to maintain bone mass. Researchers do not yet know exactly
what type and amount of exercise, hormones, or drugs might prevent bone loss
or promote bone formation. However, some combination of sex hormones growth hormones,
and exercise seems to be the key to preventing bone mass loss associated with
chronological aging and post-menopausal hormone changes on Earth.
Bone Density Assessment
Currently most medical practitioners rely on measurements of bone mineral density
to assess bone strength in patients for the diagnosis and treatment osteoporosis,.
According to the National Osteoporosis Foundation, bone density tests can detect
osteoporosis before a fracture occurs, indicate a risk of fractures, determine
an individual's rate of bone loss, and monitor the effects of treatment.
However, density measurements alone are not necessarily sufficient to manage
osteoporosis: some bones of low mineral density can function well without risk
of fracture, while other more dense bones are more susceptible to fracture. A
measure of the biomechanical properties of bone could provide a way of distinguishing
fragile from strong bones.
In order to better study bone mass loss in space, researchers at NASA and Stanford
University have developed an instrument for direct, noninvasive measurement of
bone mineral content, or stiffness, in experimental subjects that is also suitable
for Earth application. The instrument, called a Mechanical Response Tissue Analyzer
(MRTA),
determines the bending stiffness of bone, an element related to bone strength
and to its mineral density.
Bone bending stiffness is the product of bone mineral content and the geometry
or structure of bone. Using low-frequency vibrations, the (MRTA) can directly
measure bone strength. Compared to conventional radiological (x-ray) techniques
of measuring bone mineral density, the (MRTA) provides a better indication of
bone strength by taking bone structure as well as mineral density into account.
Thus far, the (MRTA) can only measure bending stiffness in two bones, one in
the arm - the ulna - and one in the leg - the tibia. A company called GAITSCAN
Inc.*, of Ridgewood, New Jersey, has already adopted this technology for commercial
marketing.
* The technology now remains with the inventor of the software (Dr. Charles
R. Steele) in the
academic environment of Stanford's School of Engineering, Division of Applied
Mechanics and in the Life Sciences Division at Ames Research Center.
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