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Collagen damage seen in older bones (2-29-00)

Researchers at The University of Texas Health Science Center at San Antonio are suggesting something new in the study of bone fractures—that the amount of damaged collagen in a bone may be directly linked to the likelihood the bone will fracture. Their studies may provide new direction in research of a problem that causes an estimated 900,000 hospitalizations nationwide each year.

Bone is a natural composite composed primarily of calcium-based mineral and an organic material known as collagen. Collagen, a fibrous protein found in skin, tendon, bone and dentin, appears to be a key component that determines bone’s ability to withstand sudden impacts, the scientists report in the February issue of Clinical Orthopaedics and Related Research. The lead author is Xiaodu Wang, Ph.D., adjunct assistant professor at the Health Science Center and assistant professor of engineering at The University of Texas at San Antonio.

Experts long have thought that bone brittleness was determined mostly by the amount of mineral in bone, as measured in bone density. But the amount of intact collagen may be just as important in fracture incidence related to age.

"Low bone mineral density has been considered to be a major cause of age-related bone fractures. In recent years, researchers have realized that reduced bone mass may not be the only factor in bone becoming brittle with age," said C. Mauli Agrawal, Ph.D., director of the Center for Clinical Bioengineering at the Health Science Center and senior author on the publication. "Researchers have found the same bone density in younger people and older people, yet the fracture rate is dramatically higher in the older group. Could it be we have been studying only half of the equation?"

A woman of 75 is seven times more likely to fracture a bone than is a woman of 45, even if the women have the same bone density, according to scientific literature cited in the paper.

Bone collagen is apparent only at the molecular level and cannot be seen by the naked eye. Scientists are attempting to see how collagen changes in bone might be prevented. About 6.8 million fractures occur each year in the United States, according to the American Academy of Orthopaedic Surgeons. Over the course of a lifetime, each person will experience two fractures on average, the academy estimates.

Dr. Agrawal, Dr. Wang and their colleagues studied bone from 33 baboons that died of natural causes at San Antonio’s Southwest Foundation for Biomedical Research. The animals ranged in age from 5 to 26 years—from young adults to the very old. Fifteen were males and 18 were females, and gender was studied as a variable.

The Health Science Center team shipped the bone specimens to collaborating Dutch scientists, who performed a biochemical process to separate damaged collagen from intact collagen. "We looked at the amount of collagen that was damaged as a function of age," Dr. Agrawal said. The study showed a 15 percent increase in the amount of damaged collagen in the oldest baboons compared to the youngest, and a 40 percent corresponding decrease in bone toughness in the older group. No significant changes in mineral content were detected.

"We are trying to replicate these exciting results in human bone samples," Dr. Agrawal said. These samples were acquired from tissue banks and the Musculoskeletal Transplant Foundation.

Researchers define bone "toughness" in terms of the energy it takes to break the bone. Fractures usually occur at impact, when energy is delivered suddenly to a specific area of the skeleton.

The San Antonio researchers conducted such tests on the baboon bone specimens. "We found that the mineral primarily determines the strength and stiffness of bone, but the collagen determines how tough it is," Dr. Agrawal said, noting that the collagen is flexible and more likely to absorb energy.

"We tend to think of bone in terms of stiff ceramic-like structure," he added. "But bone is a mixture of mineral and collagen. The ability of bone to sustain a sudden blow could be related as much to the protein content of the bone as to the amount of bone mineral."

While calcium supplements, hormone replacement and other therapies seek to prevent bone mineral loss, no current therapy can address age-related damage to a person’s bone collagen. "Although fractures are a significant problem in the elderly, the research on the role of collagen is still in its infancy and does not indicate any changes in therapies at the current time," Dr. Agrawal said. "It is our hope that in the future, someone will come up with collagen-targeted therapies."

Contact: Will Sansom