Leptin, Central Nervous System Involved in Bone Gain, Bone Loss

September 21, 2007 (Honolulu) — The discovery of a pathway in the brain that triggers osteoblast activity and the formation of bone opens the door to a new way to combat osteoporosis.

The neuromedin U pathway was described here at the American Society for Bone and Mineral Research (ASBMR) 29th Annual Meeting this week by Japanese researchers, whose work earned top honors at the meeting.

"Work by this group and other scientists has revealed a surprising finding — that bone cell activity is regulated in part by hormones and factors that are involved in the control of brain and fat metabolism," ASBMR president Steven R. Goldring, MD, professor of medicine at Harvard Medical School in Boston, Massachusetts, told Medscape.

The work was presented by Shingo Sato, MD, from the Department of Orthopedic Surgery at Tokyo Medical and Dental University in Tokyo, Japan.

"Dr. Sato and colleagues have identified neuromedin U, a central nervous system–derived molecule that helps control appetite and fat metabolism, as a potentially important regulator of bone formation," Dr. Goldring explains.

Neuromedin U–deficient mice showed a 30% higher level of bone formation and bone mass over wild-type mice, Dr. Sato's team showed.

Leptin infusions decreased osteoblast activity in wild-type mice but significantly increased bone formation in neuromedin U-deficient mice. "However, and surprisingly, intracerebral leptin infusion paradoxically increased bone formation and osteoblast number in neuromedin U-deficient mice," Dr. Sato reported.

Earlier studies showed that the beta-blocker isoproterenol inhibits bone formation in wild type-mice. In neuromedin U-deficient mice, isoproterenol had no effect on osteoblast activity.

This discovery opens the door for a way to regulate bone formation through the leptin pathway, Dr. Sato said.

Dr. Sato's work "provides insights into the role of the nervous system in controlling bone remodeling and offers potential unique and novel approaches for preventing bone loss and treating osteoporosis," Dr. Goldring declared.

"The mission of the ASBMR, the world's largest bone research society, is the translation of the highest-quality and most recent and innovative scientific discoveries into improving the care of individuals with skeletal disorders," Dr. Goldring said as he explained why the society awarded Dr. Sato and colleagues the 2007 ASBMR Most Outstanding Abstract Award.

"Understanding the mechanisms that lead to osteoporosis is a major focus of bone research. Osteoporosis is the most common bone disease, affecting tens of millions of individuals and frequently leading to marked disability and impaired quality of life," Dr. Goldring asserted.

Neither Dr. Sato nor Dr. Goldring report any relevant financial relationships.

American Society for Bone and Mineral Research 29th Annual Meeting: Abstract 1061. Presented September 17, 2007.

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