Diabetes, stem cells, and osteoporosis
It’s a relatively well-known fact that people grow fat cells in their bone marrow as they age. (If you didn’t know this, you’re not alone because I didn’t either.) As a child, one starts out with almost no fat in the bone marrow. As one ages, the bone marrow slowly turns to fat; at the age of 30, approximately half of one’s bone marrow is fat. For a long time, it was just assumed that this was part of the aging process. More recently, however, scientists have found a stem cell in the bone marrow that can turn into marrow or fat depending on the signal it receives. Those individuals with osteoporosis have much higher levels of fat in their marrow than do those without the disease. Those who take steroids to suppress the immune system also have much higher levels of fat.
What these levels of fat in the marrow means is still a matter of speculation. Even young, healthy people have fat in their marrow. Doctors think that perhaps the fat is there to act as an internal cushion of sorts, since hollow bone by itself is relatively brittle and prone to breakage. So while a knee-jerk thought might be that high levels of fat mean weak bones, this isn’t necessarily the case. Osteoporosis, which is the disease of porous and weak bones, comes as a result of loss of bone density, not high levels of fat; and it could be that increased fat levels in the marrow is one way of the body coping with this bone weakness. That’s my speculation, anyway, no one knows for sure. There’s also some thought that the fat forms as a means of storing energy, like other fat deposits found in the body.
Medical ramifications and speculation aside, what’s really interesting about all this is how the fat can be manipulated. If stem cells are placed in a petri dish and allowed to grow, they don’t remain undifferentiated stem cells for very long. They begin to differentiate into what they’re programmed to become, under the influence of the “biochemical soup” (their term, not mine) that they’re growing in. In the case of the bone marrow stem cells, adding steroid hormones causes them to turn to fat, but adding vitamin D3 caused them to turn into bone.
What does all this have to do with diabetes? Well, one of the drugs used for Type II diabetes, rosiglitazone — better known as Avandia — produced fattier bone marrow in tests on lab rats. Not a just a small amount of fat in the bones, but three times the amount as the control rats. The standard disclaimer, of course, being that thiazolidinediones — like Avandia and Actos — might not have the same result in humans since the physiologies of rats and humans are quite dissimilar. More testing needs to be done; it is not known if these drugs cause increased levels of marrow fat in humans.
And fat can be turned into bone as well. Fat taken from liposuction patients can be turned into bone by adding vitamin D, dexamethasone, and a few other things. Dexamethasone is a corticosteroid, which I find strange, because adding corticosteroids caused higher levels of fat in the marrow in previous in vitro tests , rather than promoting bone density as it seems to be doing here. Even stranger, however, is the fact that fat will turn into bone if it’s not stopped. There is a gene in the human body that must be suppressed, otherwise it will randomly turn fat into bone. This rare genetic disorder is called progressive osseous heteroplasia. Using this knowledge, researchers hope to find a drug that will cause only bone marrow fat to turn to bone. Somehow the possible side effects listed on that medication seem like they would dissuade anyone from using it: “Warning: Use of this medication may cause bone formation (ossification) in strange places. If you find bones growing where they shouldn’t, please contact your doctor or pharmacist immediately.”
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[...] Perhaps the biggest, most immediate health concern is over the density of his bones. Even with methods in place to reduce bone density loss, astronauts and cosmonauts lose an average of 1.5% of their bone density for every month they are in space, and he’s been there for almost 25 months, and it will be 27 months by the time he finally comes back home. The average post-menopausal woman loses about 1.5% of her bone density per year. So in theory if he were a post-menopausal woman, Krikalev will have lost the equivalent of 27 years of bone density when he comes back to Earth. Growing bone-mass back can be achieved, but it is a long process, and it is unknown how the quality of bone mass compares to that which was lost. Recall that bone marrow turns into fat as people age, and Krikalev has done quite a bit of aging in the last 2 years. I wonder if astronauts and/or cosmonauts take any osteoporosis drugs like Fosamax or Actonel? Hrm. I wonder who I could ask that would know… [...]
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