HU discovery could improve osteoporosis drugs

A new neural brain-to-bone pathway that controls the development of bone – which could help develop future treatments for osteoporosis and neural disorders – has been discovered by Hebrew University researchers.

The neuronal pathway – part of the autonomic nervous system – reaches the bones and is involved in controlling bone density during adolescence, which in turn determines the skeletal resistance to fracture throughout one’s entire life. Osteoporosis involves the thinning of the bones, which can result in disability and even death.

The research was published this week in the American journal PNAS – Proceedings of the National Academy of Sciences.

The researchers included scientists from HU’s bone laboratory, headed by Prof. Itai Bab, in collaboration with Prof. Raz Yirmiya, head of the laboratory for brain and behavioral research, along research students Alon Bajayo and Vardit Kram and master’s degree students Arik Bar and Marilyn Bachar. Additional collaborators were Dr. Adam Denes of the University of Manchester and Prof. Alberta Zallone from the University of Bari in Italy.

The brain monitors and regulates the physiological functioning of the internal organs through the autonomic nerve systems, which is divided into two subsystems called “sympathetic” and “parasympathetic.”

Each of these subsystems has its own distinct neural pathways. In general, the sympathetic nervous system is best known for mediating the neuronal and hormonal responses to stress. The sympathetic pathway usually functions to maintain the body’s systems when people sleep.

Previous studies by the HU researchers and others showed that the sympathetic nervous system reaches the skeleton and slows down bone development.

But until now, there was no information on skeletal parasympathetic activity there.

To show that there are indeed parasympathetic responses in the skeleton, the researchers injected a weakened rabies virus – which uniquely migrates from the injection site in the periphery of the body along nerve fibers towards the brain – into the thigh bones of mice. Following the shot into the thigh bone, the virus was found in the brain in regions known to be specific to the parasympathetic subsystem.

As in the bone and the heart, the new pathway might have an important function as well in other organs controlled by the autonomic nervous system.

“Low bone density and osteoporosis often appear together with neuropsychiatric disorders such as depression, Alzheimer’s disease and epilepsy, since interleukin-1 in the brain and the parasympathetic system are often damaged in these disorders,” Yirmiya said.

“Finding the disease mechanisms in these cases has a huge potential for the development of new therapies,” he added.

“The connection between the brain and the bone in general and the involvement of the newly discovered pathway in particular is a new area of research about which we still know very little,” said Bab.

“The new findings ... highlight for the first time an important physiological role for the connection between interleukin-1 in the brain and the autonomic nervous system,” he said.