Inhibiting a Chemical in the Intestine—Usually Associated with Mood—To Reduce Bone Loss

Karl Insogna, M.D., Professor of Internal Medicine (Endocrinology). 

The incidence of serious fractures due to the fragile bones of osteoporosis is more common in women than men, and one of every two women over the age of 50 with osteoporosis can expect to have a fracture. Current popular pharmacological interventions include the bisphosphonates, such as Fosamax.  However, these drugs can cause gastrointestinal distress, and joint and muscle aches. There are also more serious emerging concerns with these existing medications, including risks of fractures and cancer. For these reasons, consideration of new pharmacological methods to treat osteoporosis is required. Serotonin is usually thought of as a chemical in the brain that affects mood. However, 95 percent of the serotonin in the body comes from a part of the small intestine. In a wholly unexpected recent discovery, researchers found that this gut-derived serotonin, presumed to be involved in digestion, plays a critical role in regulating bone formation. Dr. Insogna and his colleagues have been at the center of key studies illuminating this connection.

Highlighted Study Findings

Preliminary research indicates that inhibiting serotonin production in the small intestine may promote bone formation, and that a treatment for osteoporosis that acts in this fashion may be possible. In his Program-funded ongoing study, Dr. Insogna is focusing on determining if intestine-derived blood serotonin levels control bone density in the general population, as they do in a previously studied family whose members have unusually strong, dense bones and inherited gene mutations that act to inhibit serotonin in the intestine. The outcome of this work will help determine if such a treatment should be pursued as a new way to treat osteoporosis. The ultimate aim is to develop an intervention to reduce or even prevent bone loss that avoids the negative side effects of current treatments.