Unlike Sir Richard Branson, most of us will remain space flight virgins. However, thanks to illuminating research by Henry J. Donahue, Ph.D., the Alice T. and William H. Goodwin, Jr. Professor and Distinguished Chair of the Department of Biomedical Engineering at Virginia Commonwealth University, we will at least learn from health-related data collected during space flights.
Unloaded=Microgravity=??
In the vein of use–it-or-lose–it, bones and muscles just don’t have as much to do in a microgravity environment where they are functionally unloaded. In fact, NASA research shows that weight-bearing bones lose on average 1-1.5% of mineral density per month during spaceflight.1
Dr. Donahue told OTW, “Prior research has shown that bone loss because of microgravity is pretty similar to bone loss that occurs in individuals as they age or in individuals on prolonged bed rest. Thus, there are any number of possibilities when it comes to using data from spaceflights for the benefit of humans on earth. In other words, therapies for spaceflight-induced bone loss will likely help prevent age-related bone loss.”
In two 2020 studies, both funded by NASA, Dr. Donahue and colleagues examined the RANKL protein, a molecule that causes bone loss/turnover, as well as how bone and muscle respond to extended periods of mechanical unloading.
NASA Cares
“All NASA-funded research must demonstrate how the work will better the human condition,” said Dr. Donahue to OTW. “Looking forward, any trip to Mars will take a year-and-a-half and will result in a substantial loss of bone and muscle for the astronauts. And because their rate of bone loss is higher than that of elderly people, the astronauts are an ideal study group.”
So, they undertook what is the first study to examine changes in bone and muscle following unloading, unloading and re-ambulation, and unloading and re-ambulation combined with acute external mechanical loading.
Dr. Donahue: “In the microgravity study we looked at something that attenuates bone loss in response to microgravity, namely, mechanical loading. We unloaded the mice bones and then tried to improve the situation by mechanically loading them. This work is important because osteopenia and sarcopenia after unloading leads to an increased risk of injury during re-ambulation. Research into what happens to the bone–muscle relationship during the reloading period may help identify new interventions for improving musculoskeletal health.”
“We found,” said Dr. Donahue to OTW, “that once bone has been unloaded, you can reambulate and the bone mass will return to normal levels. In addition, we explored the emerging concept that bone and muscle respond to their mechanical environment/unloading or loading as a unit. NASA is particularly interested in this because they want to know if we can develop single countermeasures to prevent bone and muscle loss.”
Unanticipated Results
“In the RANKL protein study we exaggerated the effect of unloading on bone to determine if it makes bone loss worse (which it should) and if makes muscle loss worse (which it did not). This suggests that bone and muscle respond to microgravity in a less than straightforward fashion; these were in vivo studies so not a lot of mechanistic data to give us insight as to why this is happening.”
“Going forward we will be looking into the role of gap junction channels in bone response to its mechanical environment. There is growing evidence that gap junction channels are very important to how bone responds to mechanical loading. To date we have found that if you block gap junction channels, bone is more responsive to the anabolic effects of mechanical load but resistance to the catabolic effect of unloading. We look forward to delving into the mechanism by which the lack of a gap junction protein is protective against unloading-induced bone loss.
Dr. Donahue says that this work will eventually lead to new therapeutic approaches to prevent disuse-related osteosarcopenia. “If we can decrease muscle and bone loss that occurs in aging and in disuse then we will decrease the chance of fracture. In addition, people will be able tolerate surgery better if their bones and muscles are stronger.”
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