Why might smoking and drinking alcohol raise the risk of osteoporosis?
14 May, 2019
Recent research has uncovered a cell mechanism that could help explain why smoking, alcohol, and other modifiable factors could raise the risk of developing the bone disease osteoporosis.
The mechanism spurs a cell type in the immune system to turn into osteoclasts, which are a type of cell that resorbs, or dissolves, bone.
It appears that mitochondria, the tiny enclosures that produce energy in cells, send out a signal that triggers this process when under stress.
When this happens in the mitochondria of macrophages, the cells turn into osteoclasts. Macrophages are prolific immune cells that remove cell waste and foreign objects by swallowing and digesting them.
The researchers behind the discovery hail from the University of Pennsylvania (Penn) in Philadelphia and the Icahn School of Medicine at Mount Sinai in the city of New York. They write about their findings in a recent FASEB Journal study paper.
"We show in this paper that when mitochondrial function is affected, it not only affects energy production but also triggers a type of stress signaling that induces the overproduction of osteoclasts," says senior study author Narayan G. Avadhani, who is a professor of biochemistry at Penn's School of Veterinary Medicine.
Some of the environmental factors, such as smoking, drinking alcohol, and certain medications, that can impair the function of mitochondria, also appear to raise the risk of osteoporosis.
Prof. Avadhani and his colleagues suggest that the stress signaling pathway that they uncovered could be the reason.
They demonstrated their findings in laboratory-cultured macrophages and mice with dysfunctional mitochondria.
Bone generation and resorption
Osteoporosis is a disease that causes bones to become less dense and more porous and brittle. This significantly increases the risk of fracture.
As people age, their risk of developing osteoporosis increases. This is because the balance between bone generation and bone resorption shifts with age.
By the time most people reach their 30s, their bone density has peaked. After that, bone density declines as the balance gradually favors resorption over generation.
According to the International Osteoporosis Foundation (IOF), 1 in 3 women and 1 in 5 men over the age of 50 will experience a bone fracture due to osteoporosis.
The IOF also estimate that around 75 million people in the United States, Europe, and Japan have osteoporosis and that osteoporosis leads to more than 8.9 million bone fractures per year worldwide.
In their study paper, the authors write that the mitochondria-to-nucleus retrograde signaling (MtRS) pathway helps cells to adapt to stress.
An earlier investigation had already led them to discover that a way of triggering this pathway can induce macrophages to differentiate into osteoclasts that resorb bone.
"However," they note, "mechanisms through which macrophages sense and respond to cellular stress remain unclear."
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