How is everyday onboard exercise on the International Space Station changing the rate of bone loss of its occupants? Can individual differences between humans explain differences in bone loss in microgravity?

Stefan Judex, an associate professor of biomedical engineering at Stony Brook University, provides insight into this quandary.

The magnitude and rate of bone loss in space are staggering: On average, astronauts lose bone mineral in the lower appendicular skeleton (the section relating to the limbs) at a rate of approximately 2 percent per month.

Currently, all space travelers exercise about two hours a day on a treadmill or with devices producing resistance against motion. The near absence of nonexercisers from the cohorts of astronauts and cosmonauts has effectively precluded proper analysis as to whether or not exercise in space has beneficial effects for the skeleton. It is clear, however, that current exercise protocols in space are, at best, only partially effective in stemming bone loss. Thus the quantity and quality of exercise necessary to prevent bone loss have not been established.

It is important to remember that there are many different forms of activity and, just like on Earth, the skeleton responds better to some than to others. While exercise is a complex stimulus that can affect many different systems within the human body (muscle, cardiovascular, neural or hormonal systems, for example), bone is primarily sensitive to the mechanical stimuli that are generated either by internal (muscle) or external (ground reaction) forces.

Most scientists agree that exercise in space poorly replicates the daily loading conditions on Earth. Unfortunately, it is not known which aspect of the mechanical loading environment should be reinforced to obtain greater efficacy: Should exercise for astronauts entail greater forces and greater rates at which the forces are applied (like impact loading)? Or should astronauts exercise more often for shorter periods of time? Perhaps the skeleton should be subjected to a much greater number of loading cycles at much smaller force magnitudes (basically, vibrations)? These and other questions are currently being addressed by a number of studies in different laboratories around the world.

While the deterioration of the skeleton in space is well recognized, the very large variability in bone loss between individuals is a much lesser known fact. Upon return to Earth after six-month missions, some individuals have lost as much as 25% of their bone structure at specific skeletal sites, while essentially no bone loss may be apparent in other astronauts. This begs the question: What exactly separates the "losers" and "nonlosers"? The identification of these differences may directly lead to the development of effective countermeasures for bone loss.

Given that all astronauts exercise in space, researchers have looked at other factors affecting bone mass to investigate whether they can account for the observed individual differences. Of these factors, the most commonly discussed are radiation, nutrition and genetics.

The factor that is the least well characterized is radiation. Currently, studies on the effects of different types of space radiation on the skeleton are rare but will likely gain prominence in the near future. At this point, there is no consensus on the impact of radiation on the skeleton during a 2.5-year trip to Mars. Regardless, all individuals on a given trip will be subjected to similar levels of radiation. Therefore, radiation by itself cannot explain the individual variability in bone mass. Similarly, nutrition is tightly controlled due to the relative lack of dietary choice (nutritional content has been optimized according to nutritional requirements in space) and is not subject to great variability.

It has long been known, however, that genetic variations between individuals account for differences in bone mass on Earth. Based on the uniformity in exercise levels, radiation and diet between individuals in space, it seems apparent that an individual's genotype may strongly influence the levels of bone loss in space. While intriguing, such a hypothesis is difficult to test directly because of the relatively small number of people who have been to space for significant amounts of time. (For statistical reasons, genetic studies typically require large sample sizes.)

Fortunately, the availability of inbred strains of mice has allowed for some testing of this hypothesis via animal models of simulated space flight. These studies have shown that, like humans, the skeleton of some genetic strains of mice are susceptible to bone loss, while other mouse strains are virtually unresponsive. Thus, genes may indeed play a large role in determining an individual's skeletal change in space. The future identification of the specific genes responsible for this trait may ultimately aid in devising strategies by which bone loss can be effectively prevented.

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