Researchers at the Columbia University College of Physicians and Surgeons have reported that bone formation may be controlled by serotonin of the gut, a naturally produced chemical that has previously been most famous for its very separate role in the brain. Ten million Americans over the age of 50 live with Osteoporosis, or fragile bones that have the potential to easily break. All current treatments, with the exception of one that is only recommended for short-term use and can be prohibitive in cost, are only able to slow bone loss rather than instigating bone formation. However, the team at Columbia University published a paper in the journal Cell in November 2008, which reports on a discovery that may affect bone formation, serotonin.
Though ninety-five percent of the body’s serotonin is made in the gut and cannot enter the brain, our understanding of serotonin outside of the brain has remained a mystery for many years. Yet, the researchers have unlocked its potential secret role in controlling bone formation. Gut serotonin is released into the blood, and the more of it that reaches the bone, the more bone that is lost. On the contrary, the less serotonin to reach the bone, the stronger it is able to become. Dr. Gerard Karsenty, the research team’s lead, was even able to prevent menopause-induced osteoporosis in mice by reducing their gut serotonin production.
Needless to say, osteoporosis researchers around the country were dumbfounded, intrigued, and excited about the findings of this report.
Clues into the potential serotonin-bone connection began with reports on a very rare, inherited condition that causes causing extremely fragile bones that can leave children with the need for wheelchairs or devices to assist in walking. The underlying problem turned out to be a mutation that inactivated a gene called LRP5. Years later, another mutation was found in the gene that caused the opposite effect, very dense bones.
Osteoporosis researchers assumed that the role of LRP5 was in the bone itself, but Dr. Karsenty’s team discovered that LRP5 actually acts upon serotonin-producing cells in the gut. While the gene has no apparent effect on brain cells that produce serotonin, it has an inverse effect on serotonin in the gut. In general, when there was more LRP5, less serotonin was made.
Dr. Karsenty further tested the theory by adding serotonin to normal mouse bone cells in the laboratory. The bone cells did in fact stop growing. He further tested this theory by feeding mice with the mutated gene a diet deficient in tryptophan, the precursor of serotonin. With significantly less tryptophan consumption, the mice could make very little serotonin in the gut and their bones did grow denser, however, animals with normal versions of the gene did not increase bone density with a tryptophan-deficient diet.
To note, osteoporosis patients tend to have normal serotonin levels. Their disease involves accelerated bone loss rather than decreased bone formation. However, the researchers are still hopeful that by creating a drug which will reduce serotonin synthesis, they will actually be able to stimulate bone growth in these patients. Of course, more research on this subject is needed, and surely scheduled on the horizon.
Reference: The New York Times, Bone Finding May Point to Hope for Osteoporosis by Gina Kolata, November 26, 2008