Astronauts may be able to lessen bone loss during spaceflight by standing on an oscillating platform for short periods. Ground-based tests have shown that genetics might indicate how bone will will respond to theis countermeasure.

Above: Genetics control 50 to 70 percent of the characteristics of bone. Above are mice bones of three different levels of density before treatment. Each strain was tested to see how it responded both to the mechanical stimulus of an oscillating platform and to disuse. Credit: Stefan Judex.

Bone loss is not an experience unique to astronauts; it is also a normal part of getting older. Once a person's skeleton has reached its peak bone mass, around age 30, it starts losing 1 to 2 percent of bone mass a decade. For women, this rate increases to 1 to 2 percent a year somewhere between three and eight years after menopause. While in micro-gravity, astronauts lose mass at the accelerated rate of 1 to 2 percent a month. When astronauts finally go to Mars, the round trip may take as long as three years. The astronauts might lose close to half their bone mass before they return, and approximately half of that loss could be permanent. In addition, the corresponding removal of calcium from bone raises the level of calcium in the blood, which increases the risk of kidney stones.

Bone Basics

Most people think of bone as a rigid, nonliving frame for the body, much like steel girders or concrete support beams. But bone is actually made up of both living tissue and a nonliving component comprising a protein matrix and minerals. Within the living tissue are cells that include osteoblasts (which are anabolic, or bone-forming) and osteoclasts (which are catabolic, or bone-eating). These two cell types work together, one eating, or resorbing, old bone back into the body, and the other replacing the old bone with fresh, new bone in response to the loads and stresses we experience during life. During spaceflight, the activity of osteoblasts slows down and the activity of osteoclasts may speed up, causing a net loss of bone density.

When humans lose bone density, some of what is lost is cortical bone, but mainly they lose trabecular bone. Cortical bone makes up the shaft of long bones such as the femur (thigh bone) and humerus (upper arm bone). Trabecular bone can be found next to joints at the ends of long bones, such as the femur ball that fits into the hip socket, and in vertebral bones. Any loss of density at such locations, where the skeleton experiences the most stress, significantly increases the risk of fractures, hence the large number of hip replacements among elderly people.

While the exact details of bone loss and restoration are still under investigation, scientists generally believe that when astronauts return to Earth, osteoclasts slow down while osteoblasts resume their normal activity level. In time, cortical bone returns to its normal density and strength. However, trabecular bone may not. Trabecular bone is organized like a lattice made up of rods and struts called trabeculae. During spaceflight, if trabecular bone loss results in a thinning of the trabeculae, the bone can be restored to its original strength. But if the trabeculae have been disrupted or destroyed, they cannot be repaired or replaced, and the bone is permanently weakened and vulnerable to fractures. This is what makes bone loss from long-term spaceflight so dangerous for astronauts.

Bone Loss in Space

Bone "adaptation" is a fairly straight-forward process: bone responds to increases in muscular or mechanical stress by getting stronger, and responds to disuse (through spaceflight, bed rest, or immobilization) by getting weaker and losing density. For astronauts, the lack of gravity's effects and regular activity greatly reduces the stress on weight-bearing bones, and the bones respond accordingly by increasing the activity of bone-removing cells and reducing the activity of the bone-building cells. This explains in large part why astronauts lose bone mass in space. While in microgravity this is not a problem, but when astronauts return to Earth or land on Mars, their bones will no longer be able to handle the renewed stress caused by the body's resisting gravity. Astronauts try to counteract the loss of bone mass caused by microgravity by challenging their skeletons with vigorous exercise while in orbit. Unfortunately, while this exercise does help reduce muscle atrophy, it is extremely time-consuming and has not proven to be a strong enough counter-measure for bone loss.

Clinton Rubin, a principal investigator at the State University of New York (SUNY), Stony Brook, has been studying bone's response to mechanical and electrical stimuli (used by nerves to cause muscle contractions) for two decades. He believes that the body's lack of vigorous physical activity in space may not be the sole cause of the bone loss and muscle atrophy common during spaceflight. Most scientists currently believe that bone mass is primarily controlled by the high-magnitude, low-frequency strain resulting from the mechanical loads on bones associated with vigorous exercise. Rubin and his associates, however, believe that a low-magnitude, high- frequency strain, such as that which the musculature continuously places on bones while a person is sitting or standing, may also have a great impact on bone morphology.

"The predominant stimulus that your skeleton experiences is not from running 100- yard dashes 20 times a day," explains Rubin. "The predominant stimulus is standing and sitting. So what is bombarding your skeleton essentially during all waking hours, during any weight-bearing activity, is a high-frequency, low-magnitude signal. This signal would, of course, diminish up in space because recruiting musculature to maintain posture is not a real problem."

Oscillating Platform Creates Stimulus

Having theorized that these low-magnitude, high-frequency signals strongly influence bone density, Rubin and his colleagues made a vibrating platform that reintroduces that type of stimulus to the skeleton. "How could I target the key sites within the weight-bearing skeleton? The way to target it is to make it bear weight," explains Rubin, and that's what his platform does. Test subjects stand on the platform — which has vibrations that are so low as to be almost undetectable to many — for 10 to 20 minutes a day.

The oscillations "trick" the body into thinking it is receiving a load-bearing strain, and bones respond by getting stronger and stiffer.

This device has already been tested in several long-term studies with animals. One study, done on rats, compared bone densities of a control group to animals subjected to different conditions. All but the control group were prevented from regular, weight-bearing activities. One experimental group was exposed to 10 minutes a day on the platform, another was exposed to normal, weight-bearing activities for 10 minutes a day, and a third group had no stimulation of any sort. The platform group maintained their bone mass at similar levels to the control group, while the other two experimental groups lost significant amounts of bone. Another study, which lasted one year, compared a control group of sheep to a group that stood on the platform for 20 minutes a day. The platform group showed a 34 percent increase in the experimental group's levels of trabecular bone, and a 26 percent increase in strength, but no change in cortical bone levels. "So we found in this group of adult sheep that this noninvasive, low-level stimulus was strongly anabolic and produced bone that resulted in the bone being stiffer and stronger," describes Rubin.

Several preliminary human trials have also been conducted on postmenopausal women and children with cerebral palsy. Both groups are at high risk of bone loss, one from aging and a reduction of hormones and the other through the lack of physical activity caused by their disease. The results have been positive and have shown minimal side effects.

These results, while still preliminary, show that the platform may be an effective counter-measure in space. Astronauts could stand on the platform a few minutes a day, even perform-ing other tasks at the same time because the stimulus is so minimal. This treatment would be much less time-consuming than the several hours of exercise currently practiced and perhaps at least as effective as current pharmaceutical measures. Rubin is still working to determine the optimal parameters of magnitude and frequency that will produce the most effective results. Plans have just begun to try to fly this platform aboard a space shuttle mission so that the investigators can start testing it on humans in orbit.

Genetics Holds the Key

One of Rubin's colleagues at SUNY Stony Brook, Stefan Judex, is studying the response of bone to stimuli from a different angle. "We and others have found that there is a great variability in bone response [among individuals in test groups] when we subject either humans or animals to mechanical stimuli," says Judex. "Certainly since genetics accounts for a large part of the form and function of the skeleton, it's obviously the next step to look at how genetics affects the sensitivity of the skeleton to either mechanical stimuli or the removal of mechanical stimuli."

The characteristics of bone are determined by three factors: genetics, mechanical loading, and nutrition and hormones. Of these three, genetics accounts for 50 to 70 percent of bone properties such as bone mass and structure, and possibly how bones react to various stimuli. Judex is investigating this relationship of genetics both to bone mass and to the bone's response to mechanical stimulus and disuse.

To test his hypotheses, Judex selected three strains of mice with different initial bone densities (both trabecular and cortical) for his research. The low-density strain had a femoral bone mineral density (BMD) of 0.45 mg/mm3, the mid-density strain had a BMD of 0.55 mg/mm3, and the high-density strain had a BMD of 0.69 mg/mm3. These strains were picked by their phenotype, or the physical characteristics of their bone density. Their genotype, or genetic makeup, controls the phenotype. Each strain was subjected to a mechanical stimulus (use of the oscillating platform) and to disuse (simulating either spaceflight or bed rest).

Unusual Results

Given that previous results from the oscillating platform have shown an unexpected degree of variability in humans, this experiment should have produced some indication as to its cause. The results were in fact rather unusual. For the low-density mice, the platform sig-nificantly increased bone formation rates, while disuse caused no change. For the mid-density mice, mechanical stimulation increased bone formation rates, and disuse significantly decreased them. For the high-density strain, neither stimulation nor disuse had any impact on bone formation rates.

These results appear to show that bone's response to stimuli is determined by the amount of bone mass already existing in the animals. However, bone mass itself is simply the phenotype, or physical manifestation, of the bone cells within the tissue (osteoblasts, osteoclasts, etc.), which are themselves controlled by genetics. "The cause of the differential sensitivity is likely the genetic variations — this is at the level of the cell, not the tissue — and not the amount of bone present, which, however, may serve as a surrogate indicator," explains Judex. "A flow chart might look like this: genetic variations, located in the cells, cause differential bone mass, which will in turn cause differential mechanosensitivity. "Judex's work on how the genetics of a particular organism such as a mouse or a human controls bone mass and affects bone's response to treatment is in the early stages. His discoveries will likely have a great impact on the ability of drugs to target bone-forming cells within problem areas of the skeleton. A better understanding of the control that genetics has over bone formation will also help scientists find better and more effective countermeasures for bone loss, both in space and on Earth.

Web Links

SpaceResearch, Volume 1, Number 4, September 2002 -- This story appeared as the Bioastronuatics Research Update in the Fall 2002 issue.

Good Vibrations -- A new treatment under study by NASA-funded doctors could reverse bone loss experienced by astronauts in space. A Science @NASA Article published in November 2001.

More information on Rubin's oscillating platforms -- Dr. Rubin's Faculty page in the Biomedical Engineering Department at the State University of New York, Stony Brook

A recent Journal article on Judex's genetics research -- Judex, S., Donahue, L., & Rubin, C. (2002, June 21). Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. Federation of American Societies for Experimental Biology Journal (The FASEB Journal 2002, Judex et al. 0 (2002): 109131)

Optimization of a Biomechanical Countermeasure for Disuse Osteopenia -- Dr. Rubin's OBPR Research Taskbook entry for FY 2001. This research is performed via a grant throught the National Space Biomedical Research Institute (NSBRI).