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Weak in the Knees - The Quest for a Cure for Osteoporosis
05.06.02
 
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.

NASA collage of pictures showing STS-96 Crew members floating in space, special shoe insoles used to monitor the mechanical forces on bones, and a process whereby vibrations are used to assess bone strength.
Image above: Left - 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. Middle - Researchers at NASA Ames Research Center use a myriad of sensors, like this shoe insole to monitor the mechanical forces on bones. Right - Using vibrations, the MRTA assesses bone strength.

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.

Photo shows bones suffering from osteoporosis (right) have a less dense structure compared to normal bone (left). Image to right: 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.

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 it 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.

Graphic shows areas most affected by fractures - the stress points at the hip and spine. Image to right: Most fractures occur at the stress points of the body like the spine and hip. Reproduced from National Osteoporosis Foundation Web site.

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.

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.

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.

NASA's Space Biology Outreach Program - Web of Life