Dec. 28, 2001 OMAHA, Neb. (DEC. 20, 2001) -- Creighton University researchers today described an important discovery in bone biology -- the location of a genetic mutation that causes high bone mass. The genetic mutation causes the opposite of the bone-thinning disease osteoporosis, which is diagnosed in more than 10 million Americans a year.
"This could be the most important discovery in bone biology over the past 40 years," said Robert Recker, M.D., director of Creighton's Osteoporosis Clinic. Dr. Recker is the physician who saw a patient in 1995 with very dense bones. That clinic visit led to the research and resulting discovery, described in the January issue of the American Journal of Human Genetics released today.
Creighton University researchers Dr. Recker and Mark Johnson, Ph.D., associate professor of medicine, collaborated with scientists from Massachusetts-based Genome Therapeutics to identify the specific gene mutation that triggers high bone mass. Randall Little, Ph.D., senior research manager at Genome Therapeutics is the article's first author. Creighton's Drs. Johnson and Recker are credited as senior authors.
The discovery is important for three reasons, said Creighton's Robert P. Heaney, M.D., an internationally recognized expert on bone and osteoporosis.
"This is the first gene found that directly seems to influence how much bone you have," he said. "It represents a new pathway that hadn't been recognized before as possibly important for bone formation, and it holds out the promise of developing agents that will stimulate the bone to strengthen itself, rather than driving that process with drugs, which is what we do now."
Researchers suggest the mutation may work by controlling the skeletal system's "set point." The idea is that bone has a thermostat-like mechanism that regulates the rate at which bone is built up or broken down. The "thermostat" is set higher for people who have high bone mass, building bone at a much higher rate than it breaks down.
"The idea of the set point is a fundamental issue in biology," said Creighton's Dr. Heaney. "No one has found one before now. This discovery could be the bone set point, and if so, there are far-reaching implications for all cell biology, not just bone research." All the body's regulatory systems, such as blood cell production, blood pressure and control of blood sugar, use set points.
When Dr. Recker saw the first patient in 1995 and conducted bone scans on her and her mother, he noticed that the bones were very dense but were shaped normally. He then turned to Mark Johnson, Ph.D., associate professor of medicine.
"There are many high bone mass genes associated with disease," said Johnson. "In all of them, there is evidence of some lesion or abnormally shaped bone. This is not the case with the gene mutation we've identified."
Creighton researchers traced the large extended family and conducted early research. (The family will not be identified to protect privacy.) They described the region on the gene where the mutation was located during a presentation at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) in 1996 and published those findings in the American Journal of Human Genetics in 1997.
After the ASBMR presentation, Creighton researchers collaborated with scientists at Genome Therapeutics, a biotechnology firm that develops pharmaceuticals and diagnostic tools based on genetic knowledge, to identify the specific protein that causes the condition.
Osteoporosis is a debilitating bone-thinning disease that occurs when bones lose mass. People with osteoporosis are more likely to break bones, especially in the hip, spine and wrist. The disease represents a major public health threat for more than 28 million Americans. Recent research suggests many people have the disease or its precursor, low bone mass, without knowing it.
Current treatments for osteoporosis prevent further bone loss, but don't help the body build significant amounts of new bone. Genome Therapeutics has partnered with pharmaceutical manufacturer Wyeth-Ayerst Laboratories to try to develop a medication that mimics the recently discovered protein's actions.
Creighton University is an independent, Catholic, comprehensive university operated by the Jesuits, who have a 500 year tradition of excellence in education. Creighton has been ranked at or near the top of Midwestern universities in the U.S. News & World Report magazine's "America's Best Colleges" edition for more than a decade.
Creighton enrolls more than 6,200 students of diverse faiths and races from across the United States and 65 countries. The student body is taught by 700 full-time faculty members in the Colleges of Arts & Sciences, Business Administration, the Graduate School, University College; and Schools of Dentistry, Law, Medicine, Nursing, Pharmacy and Allied Health Professions, and Summer Sessions.
The University is located in Omaha, Nebraska (pop. 800,000 metro area) on a 92-acre campus adjacent to the downtown business district.
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