Study Shows Hormone Affects Bone Mass

A hormone that regulates body weight and reproductive function has also been found to affect bone mass, according to a study conducted by researchers at Baylor College of Medicine.

The research could have future applications for the treatment of osteoporosis, a disease characterized by low bone mass and weakened, brittle bone structure. According to the National Osteoporosis Foundation, approximately 28 million Americans are at risk of osteoporosis, often called a silent disease which can go undetected until a bone fracture occurs.

The results of the study, which were published in the January 21 issue of the scientific journal Cell, showed that the hormone leptin acts as a bone formation inhibitor. The researchers found that a certain type of menopausal mice which should have developed osteoporosis had nearly twice as much bone mass as did the nonmenopausal mice. They used a mouse model in which the gene that encodes for the hormone leptin was missing, and determined that the difference in bone mass was due solely to the leptin deficiency.

"This is the first animal model where sterility co-exists with increased bone mass," says Dr. Gerard Karsenty, professor of molecular and human genetics at Baylor and principal investigator of the study. "That finding started the whole study."

The research team found that when leptin binds to a receptor in the brain's hypothalamus, cells known as osteoblasts receive a signal to stop building bone. This inhibition of bone formation occurred when leptin was injected near the hypothalamus of either leptin-deficient or normal mice.

Dr. Karsenty began his work with leptin after results from a previous study conducted by his team revealed that bone formation and bone loss occur independently of each other. This research, which was also conducted in a mouse model, indicated there may be a "clock" in the body telling the osteoblasts when to populate the bone or stay at the normal level, he says.

While leptin has been found to act as a bone formation inhibitor, it also performs a beneficial function in the body. Leptin alerts the brain about the body's fat levels, thus, regulating body weight. The mice that lacked leptin were obese.

The challenge is to find a way to decrease the level of leptin affecting the bone without affecting obesity, a goal that is not out of reach, says Dr. Karsenty. Ideally, an inhibitor of leptin would increase bone formation. Current drugs on the market to treat osteoporosis, like raloxifene, are used to stop bone loss. According to Dr. Karsenty, no treatment is available yet that would actually increase bone mass.

And do not forget about drinking that milk. Dr. Karsenty says that even with this potential treatment, calcium intake would still remain an important part of building bone. "What the inhibitor of leptin would do is produce the bone tissue, but calcium would be required to calcify it," he says.

The next step in the research is to find the mediator of leptin. "What are the signals coming from the brain and going to bone?" asks Dr. Karsenty. "What this study showed was that osteoporosis is not only a bone disease but a brain disease."

The next phase of research will also take place in an animal model. Dr. Karsenty projects human clinical trials could be a couple of years away.

The researchers collaborated with scientists at the National Cancer Institute in Bethesda, Md., and the University of Hamburg in Germany. The study was funded by the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Dental and Craniofacial Research.

Dr. Karsenty's co-authors at Baylor were Drs. Patricia Ducy, Shu Takeda and Jianhe Shen, all in the department of molecular and human genetics.

-LYNN FOLTIN, KRISTINA VAN ARSDEL

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©2006 Texas Medical Center

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