Bone formation appears to be controlled by serotonin, a chemical in the brain that also influences mood, appetite, sleep and metabolism. The discovery may lead to a novel treatment of osteoporosis, a disease that affects 10 million Americans older than 50.

In a paper published online Wednesday in the journal Cell, a team of researchers led by Dr. Gerard Karsenty, chairman of the department of genetics and development and the Columbia University College of Physicians and Surgeons, reports the discovery of a surprising system that appears to control bone formation. The research links serotonin produced in the duodenum to the proliferation of osteoblasts, which are cells that create new bone.

In osteoporosis, the bone mineral density is reduced, bone micro-architecture is disrupted and variety of non-collagenous proteins in bone is altered. It is most common in women after menopause (the so-called postmenopausal osteoporosis) but may also develop in men. The disease may significantly affect life expectancy and quality of life.

The scientists studied Lrp5, a gene that regulates bone formation, which lead to the discovery of a correspondence between serotonin and bone density. People with mutation of Lrp5 that cause the protein to be less active suffer from bone-weakening osteoporosis. Those who have mutations that increase the activity of Lrp5, have high bone mass syndrome.

Scientists discovered that in mice the gene that regulates bone formation controls serotonin production in the gut. The discovery lead to the hypothesis of a connection among Lrp5, its associated bone disease and serotonin produced in the gut.

Using transgenic mice, the researchers showed inactivating Lrp5 caused severe osteoporosis while overactivating Lrp5 led to higher bone mass. The mechanism through which gut serotonin controls bone formation is simple: serotonin made by the gut is released into the blood, and the more serotonin that reaches bone, the more bone is lost; the less serotonin, the denser and stronger bones become.

“The findings demonstrate without a doubt that serotonin from the gut is acting as a hormone to regulate bone mass,” Dr. Karsenty said. This is the first study to demonstrate the link between serotonin from the gut and bone formation.

Serotonin is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract of humans. In the brain, serotonin plays an important role as a neurotransmitter in the modulation of anger, aggression, body temperature, mood, sleep, sexuality, appetite and metabolism. 95 percent of the body’s serotonin is produced by duodenum, while the brain generates the other five percent.

Senior author Gerard Karsenty hopes to find a new drug that depresses the gut’s serotonin synthesis and stimulates bone growth in these patients, the New York Times reported.

Other researchers, who were not involved in the study, were very excited by this “groundbreaking” finding. Using the results of this study as parting point, perhaps further valuable treatments will soon be discovered.