Osteoporosis: Age, Not Decreased Estrogen, to Blame

Katrina Dupins

Years of research in osteoporosis at UAMS have paid off with a series of discoveries that are changing the way doctors and the public think about the bone-weakening disease.

Researchers at the UAMS Center for Osteoporosis and Metabolic Bone Diseases have shown during the last twenty years that osteoporosis is not just a disease caused by menopause, a stage when women stop producing as much estrogen.

“Estrogen loss is only one of many very important factors. We now know that it is not just a disease of women. It affects men, too,” said Stavros Manolagas, M.D., Ph.D., the center’s director, distinguished professor of internal medicine and director of the Division of Endocrinology and Metabolism in the UAMS College of Medicine.

“The idea in the beginning was, ‘If you lose estrogen, you get osteoporosis,’” he said. “The conclusion was to give estrogen to osteoporosis patients. We later discovered that estrogen causes adverse side effects including breast cancer and heart disease.”

More than 53 million people in the United States either have osteoporosis or are at high risk due to low bone mass. Osteoporosis is the major cause of fractures in people older than 50. Researchers say one in two women and one in four men over 50 will have an osteoporosis-related fracture in her or his lifetime. The costs associated with osteoporosis between 2005 and 2025 are expected to be $474 billion, according to the latest U.S. Bone and Joint Burden Report.

UAMS researchers have found that advancing age, beginning as early as a person’s 30s, causes a series of changes in bone that eventually decrease bone mass and weaken bone. Their work, according to Manolagas, has caused a paradigm shift from the “estrogen-centric” account of how osteoporosis develops to one in which age-related mechanisms intrinsic to bone are key.

The cause of osteoporosis could be very similar to the cause of other diseases of advanced age.
In another recent discovery, the UAMS investigators found that an increase in hydrogen peroxide production that comes with aging contributes to a progressive imbalance in which the body removes more old bone than it produces new bone.

More important, the UAMS group and collaborators at the University of Washington in Seattle have found that reducing hydrogen peroxide prevents not only osteoporosis but also age-associated energy imbalance, diabetes, some heart diseases, Alzheimer’s and hearing loss in mice. Manolagas believes that decreasing the production of hydrogen peroxide in cells may be a rational approach to the treatment of osteoporosis in humans.

“The cause of osteoporosis could be very similar to the cause of other diseases of advanced age like Alzheimer’s, high cholesterol and heart disease,” Manolagas said. “That’s exciting because our work shows that there is the potential to develop therapies that, for the first time, will treat multiple diseases at the same time.”

Manolagas said that a big part of the success of the UAMS Osteoporosis Center is that the researchers work as a team.

Since the UAMS Center for Osteoporosis and Metabolic Bone Diseases began in 1994, it has received more than $70 million in extramural funding. In 1999, with the help of UAMS BioVentures, Manolagas founded Anabonix Inc. to develop and commercialize drugs for osteoporosis. This company operates now in Cambridge, Massachusetts, under the name Radius Health Inc. Since June of 2014 Radius is publicly traded in NASDAQ – the first in UAMS history.