New Discovery Advances Osteoporosis Treatment

Osteoporosis may soon be easier to treat. In the Nov. 1 issue of the journal Cell, a Baylor College of Medicine researcher demonstrates that leptin, a protein associated with curbing appetite and increasing energy, regulates weight and bone formation through different pathways.

In an earlier publication, Gerard Karsenty, Ph.D., a professor of molecular and human genetics at Baylor, showed that mice lacking a leptin receptor or leptin itself are not only extremely fat with low reproductive potential, but also have more bone mass than normal mice. This demonstrates that leptin inhibits bone formation.

“This finding was truly exceptional because leptin-deficient mice are the only animal model in which menopause and high bone mass coexist,” said Karsenty. “Increased bone mass was due not to the obesity, but instead to the absence of leptin, yet we could not define at that time the precise mechanism of action of leptin on bone. The major concern then was to know whether leptin was using identical pathways to control body weight and bone formation.”

In the Nov. 1 article, Karsenty and his coworkers identify neurons in the hypothalamus that act as central controllers for leptin action on bone formation. The leptin signal on these neurons is relayed to the skeleton through the sympathetic nervous system.

In a series of experiments, Karsenty showed that the sympathetic nervous system mediates leptin action on bone formation without affecting body weight. This factor could prove important if treating osteoporosis through leptin inhibition.

“Because we can now think of leptin as a centrally placed ‘master’ regulator of body composition, we can think about interventions to control a specific component of body composition, such as bone mass, while leaving others untouched,” said Ronald Margolis, M.D., of the National Institutes of Diabetes and Digestive and Kidney Diseases, a division of the National Institutes of Health and primary funder of the study.

Karsenty also demonstrated that blocking the sympathetic nervous system activity using a widely used and safe class of drugs, beta-blockers, increases bone formation in mice. It even prevents the appearance of osteoporosis in mice without ovaries, a condition that mimics menopause.

The fact that beta-blockers could increase bone formation and prevent osteoporosis without affecting body weight offers tremendous therapeutic opportunities, said Karsenty. Studies to confirm and extend these studies are already going on in rats and in humans.

Research was additionally supported by NASA’s National Space Biomedical Research Institute, the Women’s Fund for Health Education and Research in Houston, the Fondation pour la Recherche Medicale, the Children’s Nutrition Research Center, the Societe Francaise de Rhumatologie, the Philippe Fondation, and the Arthritis Foundation.

In addition, a $2 million gift from Houston businessman C. Berdon Lawrence and his wife, Rolanette, will fund the new Bone Disease Program of Texas, established by Baylor and The University of Texas M.D. Anderson Cancer Center. The program will use discoveries made to advance the treatment of bone disease, develop an integrated research program and interactive clinical program.

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©2006 Texas Medical Center

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