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Study Suggests Target for Preventing, Treating Bone Fractures Dueto Aging, Genetic Diseases

Posted on: Wednesday, 21 December 2005, 09:00 CST

ATLANTA, Dec. 21 /U.S. Newswire/ -- Arthritis Foundation researchers have discovered a potential therapeutic target to prevent and treat bone fractures and improve the quality of bone to prevent damage from osteoarthritis and osteoporosis. These findings represent exciting news for an aging population prone to bone fractures and bone deterioration.

Bone's resistance to fracture depends on its mass and architecture, and the quality of bone matrix, the key component responsible for elasticity and toughness. Several molecular factors have been shown to regulate the mass and architecture of bone, but until now none have been shown to regulate the mechanical quality of bone matrix.

"This is the first evidence that properties of bone matrix can be regulated by a growth factor called transforming growth factor beta (TGF-beta), and that reducing TGF-beta signaling enhances the quality of bone matrix and bone mass to better resist fracture," said Tamara Alliston, PhD, senior study author of University of California, San Francisco.

The study, which will be published in the December 27 issue of "Proceedings of the National Academy of Sciences," measured the properties of bone matrix and also compared the bones' resistance to fracture in a bending test. Researchers found that in mice with high levels of TGF-beta, the bone was less resistant to fracture and the bone matrix was less elastic, less durable and contained lower levels of calcium phosphate. However, animals with low levels of TGF-beta had more bone mass and a higher resistance to fracture, a higher mineral concentration and more elasticity in the bone matrix.

The findings suggest that TGF-beta could be targeted for clinical intervention by reducing TGF-beta signaling at the relevant site in the body. Modifying the TGF-beta pathway may improve the quality of bone or expedite bone repair following a fracture, joint replacement surgery, dental implants or bone grafting. The study also has exciting implications beyond musculoskeletal conditions. Building on evidence that cancer cells increase TGF-beta levels when they metastasize to bone, clinical trials are being developed to test whether a TGF-beta inhibiting drug prevents metastasis to bone and reduces damage to bone tissue.

The U.S. Surgeon General warns that by 2020, one in two Americans over age 50 will be at risk for fractures from osteoporosis or low bone mass if no immediate action is taken (see note). The risk of bone fractures and bone deterioration increases with age and is often associated with changes in metabolism. Due to the decrease in estrogen production, postmenopausal women are especially vulnerable. In addition, people with arthritis are at increased risk for the development of osteoporosis.

"With nearly 40 million Americans over age 65 and the first wave of baby boomers nearing 60, preventing and treating conditions facing aging boomers is critical," said Dr. John H. Klippel, president and CEO of the Arthritis Foundation. "Dr. Alliston's findings are an important step toward the understanding of the therapeutic targets that should be considered in treating bone disorders."

The Arthritis Foundation is the only nationwide, nonprofit health organization helping people take greater control of arthritis by leading efforts to prevent, control and cure arthritis and related diseases -- the nation's number one cause of disability. The Arthritis Foundation is the largest non-governmental funder of arthritis research in the world. Since 1948, the Arthritis Foundation has provided nearly $350 million to arthritis-related research through its nationally recognized peer-review research award program.

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NOTE: Bone Health and Osteoporosis: A Report of the Surgeon General, October 2004

http://www.usnewswire.com

Source: U.S. Newswire

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