Behind the Scenes of Bone Loss in Microgravity Environments
What actually makes bones lose their density in microgravity environments? Hint: genes.
Brittle bones are not a humerus subject on the International Space Station (ISS).
Osteoporosis is a reality for many elderly people and those with genetic conditions… but especially is a threat to healthy astronauts. In fact, to combat health effects, astronauts in the ISS workout 6/7 days a week for 2.5 hours a day (The Verge). That’s quite the workout!
Our bodies are not used to microgravity environments. For example, blood flow relies on gravity to circulate the body. Gravity pushes blood down to the legs and lower areas of your body.
When there is no gravity to pull your blood circulation down… blood concentrates in your head. This creates puffy face syndrome (NASA).
Also, astronauts’ legs become thinner (it’s called bird leg) because there is less blood concentration in the lower areas of your body.
Our bodies aren’t built for space. Just by spending a few weeks in a microgravity environment…the health effects are the same as being on one lengthy bed rest (MJ). One of the biggest changes our body faces is bone loss.
Every month in a microgravity environment, the bone loses minerals and starts losing density at a 1–2% rate (Reach). To put this into context, elderly people on Earth lose density at a rate of 1–1.5% every year (Men’s Journal). This loss in a microgravity environment is especially prevalent in weight-bearing bones, such as the calcaneum (bone found in the heel of the foot) and the tibia (shin bone).
To understand this rapid bone loss, let’s take a dive into the genetics and cell reaction to microgravity.
But first, we have to understand the nature of bones here on Earth.
Bone crash course 101
Bone is a dynamic tissue. Tissues are a group of cells that work together to form a specific function… out of these cells, there are two very important ones to note: osteoclasts and osteoblasts.
Osteoclasts and osteoblasts work together to reconstruct old bones into new ones. This process is called bone remodeling-a lifelong and natural process. It’s mandatory to repair bone damage and maintain normal calcium levels in the body.
Remodeling looks like:
a) Bone resorption
Osteoclasts resorb old bone tissue.
Osteoblasts form new bone tissue.
Osteoclasts and osteoblasts work together. The balance between osteoblastic and osteoclastic activity is important to maintain bone mass. Balance doesn’t mean that the osteoblast population is the same as the osteoclast. It means that they should co-exist in a healthy ratio.
Based on a research paper, 2 osteoblast : 1 osteoclast is the most appropriate ratio.
Bone marrow-derived mesenchymal stem cells (BMSC) monitors the balance. BMSC can develop to be osteoclasts or osteoblasts, which is why it can monitor and regulate balance.
This balance is ruined in a microgravity environment.
Bones in microgravity
There are more osteoclasts created than osteoblasts. This means that there are more resorption and deconstruction of bone tissues than rebuilding… so of course over time, your bones get more brittle.
There are several factors that influence the change in cell production and balance. The important 2 to note are the disruption of stress fibers and change in the RANKL/OPG ratio.
Disruption of stress fibers
Within 7 days of exposure to microgravity, the F-actin stress fiber in human BMSC completely disappeared. While monomeric G-actin increased. In addition to this, RhoA expression was reversed, eliminating stress fibers.
(Research conducted by Meyers)
As a result of disruption… osteoblastogenesis activity decreases*, adipogenic differentiation increases¤, and osteoclastogenic activity increases¢.
* fewer osteoblasts are produced.
¤Stem cells form more adipose tissue (fat that stores energy) instead of more important cells.
¢ More osteoclasts are made.
RANKL: OPG ratio is screwed
RANKL and OPG ratio is a major determinant of bone mass.
In case you wanted to know: RANKL is the abbreviation of receptor activator of nuclear factor Kappa-B ligand.
OPG is the abbreviation of osteoprotegerin.
RANKL is an apoptosis* regulator gene. It modifies protein levels such as Id4, Id2 and cyclin D1. Also, RANKL plays an important role in bone remodeling/bone metabolism.
- *apoptosis is a fancy way of saying “programmed cell death.”
As for background context of OPG…You just need to know that OPG physiologically counterbalances RANKL. Also, osteoblasts make OPG.
OPG and RANKL ratio is extremely important to be maintained. However once again, the ratio gets screwed under a microgravity environment: Osteoblasts make less OPG(research conducted by Rucci). In other words, there is less OPG made and more RANKL made.
This increases RANKL : OPG ratio. An increase in ratio simulates more pre-osteoclast differentiation, which means that there are more osteoclasts are being made → more bone absorption happens.
Let’s use a visual to summarize the findings of multiple experiments regarding bone loss.
In a microgravity environment…
- Less OPG is made. This means that the OPG and RANKL ratio becomes irregular. Irregularity simulates the increase in the production of osteoclasts.
More osteoclasts =More bone absorption
- Mesenchymal Stem(which is another way of saying BMSC) makes fewer osteoblasts.
Fewer osteoblasts =Fewer cells to build new bone tissue
- The disruption of stress fibers increases the production of osteoclasts. This explains why there are more osteoclasts made from pre-osteoclasts.
Again, More osteoclasts =More bone absorption
Different genes are turned on during microgravity environments. And these changes, change the production of osteoclasts and osteoblasts… ultimately creating more osteoclasts than osteoblasts; meaning, that there are more cells to destruct old bone tissue than make new.
This explains why bone loses its density in space.
My own take on it:
More research should be conducted about the nature of BMSC cells and gene expression in microgravity environments. Hopefully, we can come up with a new and more effective solution to combat bone density than exercise. Gene-editing might just be the answer.