NEW STUDY. For the first time, researchers at Sahlgrenska Academy are now demonstrating a clear connection between serotonin in the blood and the risk of fractures. Almost one thousand men are included in the study, in which those with high blood serotonin levels had hip fractures more than twice as often.
The hormone serotonin is often described as a neurotransmitter. Its most famous function is as a neurotransmitter in the brain, where serotonin is primarily important for depression. Sahlgrenska Academy’s Nobel laureate Arvid Carlsson was among those to make significant contributions to knowledge about the role of serotonin in the brain.
But serotonin is also in the rest the body. However, the hormone does not cross the blood-brain barrier and may not have to have the same effects in the brain as in the rest of the body.
In blood circulation, serotonin is primarily an intestinal hormone. In the human body, serotonin is formed in the gastrointestinal tract, where it regulates intestinal motility. The hormone also regulates blood vessel tone. There has been speculation that serotonin also plays an important role in skeletal regulation, because all types of bone cells have receptors that bind to serotonin. The results from Sahlgrenska Academy now show, for the first time, that the risk of osteoporosis and injuries from falls are connected to blood serotonin levels.
“It has been known that smokers have higher serotonin levels and that they also have increased risk of developing osteoporosis. It is also known that people who have been taking SSRIs for a long time, selective serotonin reuptake inhibitors for depression, are more commonly affected by fractures. But our study is the first to really map out the connection between serotonin in the blood and fractures,” says Dan Mellström, who is the last author of the study and who has long been an adjunct professor at Sahlgrenska Academy.
Doubled risk of hip fractures
The study includes blood samples from 950 men who are part of the population study MrOs (Osteoporotic Fractures in Men) in Gothenburg. Blood samples that were collected in 2001–2004 were frozen at that time and the serotonin levels in the samples have now been analyzed. The serotonin levels were then compared with the fractures that actually occurred during the more than ten years that have passed since the blood samples were collected.
“When we analyzed serotonin levels in the blood samples, we divided the results of the analyses into five parts, or quintiles,” says Hallgerdur Lind Kristjansdottir, doctoral student in the Department of Internal Medicine and Clinical Nutrition at Sahlgrenska Academy, and the study’s first author. “When we compared data to the fractures that occurred, we saw that hip fractures were 2.3 times more common in the fifth of men with the highest serotonin levels, compared with those in the other four groups. This is a strong statistical correlation.”
Hallgerdur is a doctoral student in a project studying the connection between blood formation and bone formation. Her supervisor is Catharina Lewerin, and Dan Mellström is assistant supervisor.
In the study, the researchers have taken into account the factors known to increase fracture risk, such as age and smoking. Men who took SSRIs were not included in the study.
More and more medications affect serotonin
The findings are published in the Journal of Bone and Mineral Research (JBMR), whose editorial board also chose to feature the study in an editorial. In this article, Peter Vestergaard, professor of clinical medicine at Aalborg University Hospital, concludes that the connection the study presents between blood serotonin levels and the risk of fractures should be interpreted cautiously. He says the findings may still be cause for concern, because the use of pharmaceuticals that affect serotonin levels is increasing, including in patients with depression and diabetes. In addition to the increased risk of fracture potentially entailed by the underlying diseases themselves, increased fracture risk may be a potential side effect of the medication.
Dan Mellström does not believe the study will have any clinical significance in the short term, but he does believe the findings may increase interest in serotonin in the blood among researchers. He says that the findings should interest cardiovascular researchers, because the blood thinners taken by many patients to prevent heart attack and other cardiovascular diseases affect thrombocytes in the blood and indirectly levels of serotonin, which also has significance for bone metabolism.
“Even though all blood is formed in bone marrow, the relationship between bones and blood is not as obvious to all researchers, but I believe interest is increasing. Several studies are underway in other countries, and in just the last six months, vast quantities of data have been collected,” says Dan.
Different effect on muscles and bones
High serotonin levels are weakly connected to lower bone strength but have the reverse effect on muscle strength. People with high levels of the hormone have greater muscle strength than those with low serotonin levels. Falls are an important factor for fractures, and in this study, men with low blood serotonin levels had fallen more often in the past year.
“Serotonin has a negative effect on bones but appears to be positive for muscles. This is the first time we’ve seen a hormone have different effects on musculature and bones,” says Dan Mellström, who recalls how, many years ago, he discussed serotonin from an evolutionary biological viewpoint with Arvid Carlsson. “Arvid realized then that the hormone was probably involved in an old fight-or-flight instinct, during a period many thousands of years ago when it was important for the body to be able to control energy to the muscles, breathing, lungs and heart, while energy consumption in the intestines and bone formation was taken down to a minimum. It’s a compelling idea, but much research remains to be done on the role of serotonin in the body.”
JOURNAL: Journal of Bone and Mineral Research (JBMR)
TITLE: High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures: The MrOS Sweden Study
AUTHORS: Hallgerdur Lind Kristjansdottir, Catharina Lewerin, Ulf H Lerner, Ewa Waern, Helena Johansson, Daniel Sundh, Magnus Karlsson, Steve R Cummings, Henrik Zetterberg, Mattias Lorentzon, Claes Ohlsson, and Dan Mellström.
Article: https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3443
TEXT: ELIN LINDSTRÖM CLAESSEN
