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For other articles and previous issues click here. August 2, 2004 Lost
in Space: Bone Mass The International Space Station and a planned mission to Mars have scientists working to fully understand—and possibly prevent—bone mineral loss caused by long periods of weightlessness in space. Traveling in space affects the human body. Among the effects astronauts have reported from floating weightless are nausea, disorientation, and irregular sleep patterns. Astronauts find that most of these conditions disappear as soon as they return to Earth’s gravity. There is at least one condition, however, that astronauts experience during prolonged space travel that may not be reversible. The loss of bone mass—as doctors know from seeing people with osteoporosis—can lead to fractures and other serious musculoskeletal problems. With NASA planning longer space missions on the International Space Station (ISS) and to Mars—where the round-trip could take three years—bone loss from weightlessness poses an issue scientists must consider for the health of space travelers. NASA-funded researchers and those with the National Space Biomedical Research Institute (NSBRI) are studying bone loss in weightless conditions and working to develop measures that would counteract this loss. Bone loss is not unique to space travelers; it’s a normal part of aging. Studies show that after a person’s skeleton reaches its peak bone mass—around the age of 30—it starts losing bone mass at the rate of 1% to 2% per year. For women, the rate increases to 3% to 5% per year for the three to eight years after menopause. According to the National Osteoporosis Foundation, at least 25 million people in the United States suffer from bone loss, resulting in a direct cost of more than $18 billion per year to national health programs. That large cost is why NASA hopes bone loss research could aid people on Earth who suffer from osteoporosis and other similar conditions, as well as those who are immobilized by injuries or genetic conditions, says Victor Schneider, MD, the chief for clinical research in the bioastronautics research division at NASA’s Office of Biological and Physical Research in Washington, D.C. Astronaut Study The crew members, 13 men and one woman ranging in age from 40 to 55, spent four to six months aboard the space station during various missions. Bone density measurements were taken of their hips, spines, and heels before and after their trips into space. Preflight procedures were usually performed 30 to 60 days prior to launch and postflight measurements were normally performed within seven to 10 days of landing. Measurements were also taken one year after returning. “It would have been ideal to measure bone loss while in flight, but that is not possible at the current time,” Schneider says. NASA is training astronauts to use portable ultrasound machines, which they may be able to use to take periodic in-flight bone density measurements. (We reported on the ultrasound system on the space station [“To Infinity and Beyond: Ultrasound in Space”] in the June 7 issue of Radiology Today.) The UCSF/Baylor study used 2-D and 3-D imaging methods to identify bone density loss. Researchers hoped to measure the amount of bone loss and more specifically where in the skeleton it was the greatest. First, the researchers used 2-D dual x-ray absorptiometry (DEXA), the standard clinical imaging tool used to measure bone loss in people on Earth. The preflight and postflight DEXA scans of the astronauts showed they were losing 1.2% to 1.6% of bone mass per month from the hip and approximately 1% per month from the spine—much more than postmenopausal women typically lose. More than 10 years earlier, researchers had used DEXA scans to measure bone loss in an astronaut crew aboard the Soviet/Russian space station Mir. Those studies also found that the astronauts aboard Mir were losing 1% to 2% of their bone mass each month. “This study demonstrates that bone loss occurs in space station crew members at a rate comparable to that observed in the crew of the Russian Mir spacecraft,” Lang says. The UCSF/Baylor study also used CT imaging with volumetric rendering, adding a third dimension to quantify spaceflight-related bone loss in the hip and estimate changes in hipbone strength. Bone Types CT measurements in the hip were performed preflight and postflight to measure bone loss in the porous bone in the interior of the hip and in the dense outer shell of the hipbone. Using CT allowed the researchers to identify the place on the bone where bone was lost, Schneider says. On average, the ISS crew lost trabecular (interior bone) at a rate of 2.2% to 2.7% for each month in space and cortical (outer bone) at a rate of 1.6% to 1.7% per month. Using information from the quantitative CT images, the investigators also projected changes in hipbone strength. They estimate on average that hipbone strength declined by 2.5% for each month of flight. The researchers also analyzed loss of density in vertebrae. Hips and vertebrae are the skeletal sites associated most with serious osteoporosis-related fractures in older adults, Schneider points out. The study found on average that the ISS crew lost vertebral bone at a rate of 0.8% to 0.9% per month, which was also consistent with data from earlier long-duration missions, Schneider says. The study also used quantitative ultrasound measures of the heel, which were taken at the same time as the CT and DEXA scans for comparison. However, the ultrasound measurements were not as useful as the CT and DEXA scans, the researchers report. Comparing DEXA and quantitative CT is helpful because DEXA scans measure area density, which depends on the mineral content and size of the bone, while quantitative CT measures volumetric bone mineral density, Schneider explains. CT scans aren’t routinely used to measure bone in patients on Earth because it is more difficult and a more costly imaging method. Why Bone Loss Happens When humans lose bone density, much of what they lose is trabecular bone. Trabecular bone can be found next to the joints at the ends of long bones, such as the femur ball that fits into the hip socket, and in vertebral bones. These are the areas where the skeleton experiences the most stress. Thus, any significant bone loss in these areas significantly increases the risk of fractures. The bone density loss in outer space occurs quickly. As a result, an astronaut who is in space for six months could lose as much as 10% to 15% of his or her pre-flight bone mass, Schneider says. It’s not known how quickly or how much bone the astronauts can regain once they return to Earth and gravity. However, researchers have observed a significant delay in regaining bone mass. Preventing the Problem Preliminary studies indicate that zoledronate, administered once intravenously, can significantly decrease the amount of bone loss, says Jay Shapiro, MD, professor of medicine at Uniformed Services University of the Health Sciences in Bethesda, Md., and a member of the NSBRI bone loss team. In a study conducted over the last three years, 17 patients between the ages of 18 and 50 immobilized by spinal cord injuries were given the medication and observed for one year. Their bone loss was found to have decreased significantly. “While the results suggest that bisphosphonates could be an effective countermeasure to bone loss, due to weightlessness in microgravity, the answer awaits in-flight testing on the International Space Station,” Shapiro says. LeBlanc has also shown that an oral bisphosphonate, alendronate, a drug produced by Merck, prevents bone loss in normal people who are restricted to bed rest for four months. Another study at State University of New York (SUNY) Stony Brook is looking at using extremely small vibrations as a countermeasure for microgravity-induced osteoporosis. The idea is that the vibrations could mimic what active muscles do when the body is taking short, quick steps. Perhaps in this way, the skeleton could be “tricked” into thinking it is still subject to the Earth’s gravitational loading, says Clinton Rubin, PhD, professor and director of the Center for Biotechnology and chair of the department of biomedical engineering at SUNY Stony Brook and a national expert on osteoporosis. Rubin and his colleagues have developed a bathroom scale-like object that “shakes” at 30 cycles per second, which is similar to the frequency at which muscle is active. First running tests in mice, rats, and sheep, they have shown that exposure to such mechanical signals can increase bone mass and improve bone strength. Future Possibilities The research was done in collaboration with Zulf Mughal, MD; Judith Adams, PhD; and Kate Ward, PhD, at the University of Manchester in England and was published in the March issue of the Journal of Bone and Mineral Research. “We are now working with Juvent, Inc., a new [December 2003] medical device company to develop the technology further,” Rubin says. Juvent plans to begin marketing the device in Europe by the end of this year. It is also developing a protocol to begin the FDA-required phase 3 clinical study in the United States for a bone mineral density label claim. Rubin is also working with a colleague at SUNY Stony Brook, Yi-Xian Qin, PhD, an associate professor of biomedical engineering, who is developing a low-mass, compact, noninvasive diagnostic tool that uses image-based scanning ultrasound technology to measure bone quality. DEXA, which provides 2-D representation of bone mineral density, does not provide information on a bone’s physical properties per se. But recent advances in quantitative or scanning ultrasound have enabled a true characterization of bone quality, including both bone mineral density and mechanical strength. The machine attempts to measure not only the density of the bone but the quality—how much risk is the bone for fracture. The challenge, Qin says, is to develop the machine so it is small, lightweight, portable, and offers high resolution so space crew can use it while on a lengthy mission. Qin has built an experimental prototype machine—roughly the size of two shoeboxes—that he has tested on sheep and pigs. That machine is currently being used for clinical trials for osteoporosis patients on Earth. “We will try and use this as verification to see if our machine is capable of picking up changes that indicate bone loss,” he says. “The next step would be to develop a machine for use aboard a space flight.” — Beth W. Orenstein is a freelance health writer and regular contributor to Radiology Today. |
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