Outsmarting osteoporosis
Virginia Bowden, Ph.D., loves the slopes of Telluride, Colo., where she and her husband, Charles Bowden, M.D., own a condominium. “We’ve been skiing since the 1970s, currently about 30 days a year,” she said. “For me the appeal is the mountain views.” In 1997 she fractured her hip while skiing at Winter Park. The bone did not heal after the Colorado surgeon inserted a pin, so the following year she underwent a hip replacement at University Hospital in San Antonio. The surgeon sent a bone specimen for clinical testing, which revealed osteoporosis.
Nearly 40 million Americans suffer from osteoporosis or are at high risk for it, according to the National Institutes of Health. This bone-thinning disease is expected to cause fractures that, by 2025, will have cost patients $25 billion to repair. Osteoporosis is most common in post-menopausal Caucasian women, some of whom live their days with the knowledge that a fracture can result from stumping a toe, getting into bed or sneezing. There is great need for translational research to speed scientific discoveries to patients. Two exciting findings in the Long School of Medicine at the UT Health Science Center San Antonio hold new promise to reduce the suffering caused by bone loss.
Dr. Bowden, director emeritus of the Health Science Center libraries, is a patient of Jan Bruder, M.D., endocrinologist with UT Health Physicians, the clinical practice of the Long School of Medicine. Dr. Bruder sees patients during a weekly osteoporosis consult clinic at the Medical Arts & Research Center. “I’ve been going to Dr. Bruder annually since that time,” Dr. Bowden said. “I know what my treatment is, and I think in some ways it was good to find out I had this tendency, so I know to take my calcium, exercise and do the things I should do anyway.”
Bone is constantly remodeling — older bone is removed and new bone forms. Exercise places mechanical loads on bone, resulting in a healthy balance of new and old. “The need for regular exercise extends far beyond its role in reducing body fat to maintain a healthy body,” said Jean Jiang, Ph.D., professor of biochemistry in the Long School of Medicine and member of the Sam and Ann Barshop Institute for Longevity and Aging Studies. “It is equally important for maintaining healthy bones to avoid osteoporosis and bone loss during aging.”
Building bone UT Health Science Center researchers discovered a naturally occurring process in bone cells. This “lock-and-key” system can be linked to pressure bones experience from exercise, walking and regular daily activities. Investigators are evaluating the system for clues to finding new therapies to prevent osteoporosis.
Dr. Jiang’s laboratory discovered novel information about how bones, one, sense the loads being applied to them and, two, release growth factors to build new bone. The report in Proceedings of the National Academy of Sciencesspurred sufficient interest to become an Editor’s Choice article in the journalScience.
Dr. Jiang’s team discovered a lock-and-key system in load-sensing cells. A protein (integrin α5) acts as a key to open the locks, which are channels on the cells’ surface. This releases molecules that trigger bone remodeling. “Our study links the effect of mechanical forces directly to the anabolic (or growth) function of the bone,” Dr. Jiang said. “This novel finding could be very useful for development of therapeutic targets to promote the opening of the channels and permit the release of bone growth factors.”
Such knowledge could prevent the bone weakening and loss caused by osteoporosis, she said.
Barshop Institute member Brian Herman, Ph.D., is professor of cellular and structural biology in the Long School of Medicine, special assistant to the president of the Health Science Center and a Chancellor’s Health Fellow in Collaboration with The University of Texas System. His team published studies on age-related osteoporosis in mice. The Herman laboratory found that increasing the genetic expression of a protein called caspase 2 prevented osteoporosis development in the rodents. Their bones were 30 percent stronger than the bones of mice lacking caspase 2 expression.
“We are looking at whether caspase 2 can enhance fracture healing,” Dr. Herman said. “Our plan is to license technology based on this finding or think about starting a company ourselves.”
More-effective, better-tolerated treatments for bone health are needed. Bisphosphonates are the most frequently prescribed medications for osteoporosis. With continuing use, these drugs can cause nausea, abdominal pain, difficulty swallowing and risk of esophageal inflammation and ulcers. In 2010 the National Osteoporosis Foundation issued new treatment recommendations; one was for patients to take drug holidays. “There are side effects of long-term treatment of osteoporosis, and based on bone density and risk factors some people who were previously started on therapy would not be started today,” Dr. Bruder, also a Barshop Institute member, said. “This is not to say that patients can go untreated, however. If you need to be on therapy, you need to be on it.”
Dr. Bowden served the Health Science Center from 1970 to 2003, including as library director from 1985 to 2003. Her osteoporosis medication is re-evaluated once a year. For three years she received an annual infusion; Dr. Bruder said it was not necessary this year.
The loads from exercise on the Colorado snow continue to strengthen her bones. “I’m still skiing,” Dr. Bowden said. “I stick with the intermediate-level areas and try not to fall. I was knocked down this past year on Christmas Eve by a snowboarder and broke my collarbone. The ski patrol came quickly and took me to the clinic. The bone healed within a month and I was skiing again. It (osteoporosis) hasn’t slowed me down.”
