LOS ANGELES, June 13, 2006 (PRIMEZONE) -- Clinton T. Rubin, Ph.D., an internationally known biomechanical engineer who has developed efficient non-pharmacological methods of enhancing bone mass using low-grade mechanical stimulation, was featured in The Saban Distinguished Lecturer Series at The Saban Research Institute of Childrens Hospital Los Angeles on Friday, June 9, 2006.
Dr. Rubin, professor and director of the Center for Biotechnology, which is a New York State Center for Advanced Technology in Medical Biotechnology, at the State University of New York at Stony Brook, discussed, "The Development and Application of Non-Pharmacological Intervention for Osteoporosis: From Barnyard to Bedside and Beyond."
"Originally, the intent of the treatment which Dr. Rubin developed (delivering low-grade mechanical stimulation through a device known as an oscillating plate) was to ameliorate bone loss in elderly women with osteoporosis," said Vicente Gilsanz, M.D., Ph.D., director of the Bone and Body Composition Initiative at The Saban Research Institute. "However, at Childrens Hospital, we are testing its effectiveness for enhancing bone mass in children with musculo-skeletal deficiencies." Dr. Rubin and Dr. Gilsanz recently completed the study on young 16-to-21-year-old women, demonstrating that bone and muscle mass can increase with these extremely low-level signals.
Dr. Rubin's work is particularly relevant to osteoporosis, a common skeletal disorder characterized by deterioration of bone strength and atraumatic fractures, most frequently at specific load-bearing sites of the skeleton.
Dr. Rubin and his colleagues at the Center for Biotechnology, which links the intellectual and physical resources of the New York universities to the biotechnology, pharmaceutical and medical device industries, showed that high-frequency/low-magnitude vibrations increase bone mass in animal models and clinical studies, a potential means to intervene in subjects genetically predisposed to low bone density.
Dr. Rubin theorized that osteoporosis can be prevented in young adulthood, or perhaps even adolescence. "This builds on my long-term collaboration with Dr. Gilsanz and our efforts to translate our basic science on bone's sensitivity to mechanical signals into a non-drug-based therapy for metabolic bone diseases such as osteoporosis," he said. "Our work is trying to provide the basis for treating osteoporosis 40 years before it actually occurs... and all without having to consider the potential risks versus benefits of long-term drug treatment."
Dr. Rubin explained how the treatment works. "Any physiologic system you have that perceives a stimuli -- the way we you see color, or hear the change of tone of voice -- is all frequency dependent. Why not bone? Why can't bone be frequency-sensitive, too?
"As you age, the principal mechanical signal to the bone dissolves away. Even though the elderly are active, the predominant signal is no longer there... so we proposed to put that signal back in," through an extremely subtle series of vibrations delivered through the oscillating plate. "Vibration, as a surrogate for exercise, can be used as a passive exercise to mirror muscle activity through these extremely small mechanical signals, which stimulates bone growth," he said.
In a clinical trial testing the device on elderly women, researchers noticed distinct improvements in the women's bone density. "Maybe there's something to the low-level mechanical signal... Maybe these women are actually missing a signal that we're replacing."
Dr. Rubin offered a physiologic basis and biologic evidence for bone's sensitivity to low-magnitude mechanical signals, and showed how it can be both anti-resorptive and anabolic (bone-producing) to the skeleton. "So, if everyone appreciates that 'exercise' is good for the skeleton and helps inhibit osteoporosis, the questions become what 'part' of exercise is bone actually responsive to, and can you distill out the 'important' parts and create a sort of 'passive exercise?'"
Dr. Rubin has used basic science to build a case for using this intervention in the clinic. "Think of it, rather than bench to bedside, a time-worn cliche of bringing basic science into the clinic, that instead I'm trying to go from the benchtop to the barnyard (through sheep and turkey experiments) to the bedside (three clinical studies, including one at Childrens Hospital Los Angeles) to beyond (our status in putting this technology in the international space station)."
Delivered through safely controlled exposures to the oscillating plate, the treatment has broad implications as a preventive therapy in medicine. "After age 35, most people tend to lose two to three percent of bone per decade," explained Dr. Rubin. "Women after menopause lose two to three percent per year. In space flight, astronauts lose two to three percent per month."
Dr. Rubin believes that older people who suffer from osteoporosis and bone fractures had low bone density when they were children. Therefore, the device also might one day be routinely used in children with low bone density. "The treatment may some day present an alternative to drug therapy as a means to prevent osteoporosis," Dr. Rubin said.
Dr. Rubin's research has combined basic laboratory work and clinical studies to better characterize the molecular mechanisms that regulate the bone adaptive response triggered by a variety of biophysical stimuli. The ultimate goal of his research is to improve diagnosis of skeletal diseases and to explore the therapeutic promise of mechanical stimuli as a non-pharmacological treatment approach for metabolic bone diseases, devising strategies to inhibit osteopenia, accelerate fracture healing and promote bony ingrowth into prosthesis.
Dr. Rubin's work is funded by the National Institutes of Health, the U.S. Army and the National Aeronautics and Space Administration.
Dr. Rubin, who is professor of orthopaedics, anatomy, molecular biophysics and mechanical engineering at the S.U.N.Y., Stony Brook, has been director of the Musculo-Skeletal Research Laboratory since 1987, and he has been director of the Program in Biomedical Engineering since 1995. He has been director of the Center for Advanced Technology in Medical Biotechnology, New York State Office of Science, Technology and Academic Research since 1997.
Dr. Rubin was named the leading professor and founding chair of the Department of Biomedical Engineering in the College of Engineering and Applied Sciences and School of Medicine at Stony Brook in 2000.
A Fellow of the American Institute for Medical and Biomedical Engineering, Dr. Rubin has received multiple awards, including the Development Award from the Whitaker Foundation, the Elizabeth Winston Lanier Award from the American Academy of Orthopedic Surgeons and the Calgary Award in Orthopaedic Biomechanics. He holds several patents and is the co-founder of several start-up companies as a result of his translational research studies.
Founded in 1901, Childrens Hospital Los Angeles has been treating the most seriously ill and injured children in Los Angeles for more than a century, and it is acknowledged throughout the United States and around the world for its leadership in pediatric and adolescent health. Childrens Hospital Los Angeles is one of America's premier teaching hospitals, affiliated with the Keck School of Medicine of the University of Southern California for more than 74 years. It is a national leader in pediatric research.
Investigators at The Saban Research Institute are working to create a world in which all children are healthy -- a world in which they are no longer threatened by such diseases as cancer, congenital heart defects, diabetes, sickle cell anemia, epilepsy, immune deficiencies and respiratory disorders. They ask basic questions about human biology, find new ways to see inside the body, explore genetic mysteries, develop promising drug treatments and test preventive strategies -- scientific inquiries that benefit both children and adults.
Programs and initiatives at The Saban Research Institute include the Body and Bone Composition Initiative; the Cancer Program; the Cardiovascular Research Program; the Community, Health Outcomes and Intervention Research Program; the Developmental Biology Program; the Gene, Immunology and Stem Cell Therapy Program; the Imaging Research Initiative; the Microbial Pathogens Initiative; and the Neuroscience Program. Clinical research is conducted under the auspices of the Center for Endocrinology, Diabetes and Metabolism; the Childrens Center for Cancer and Blood Diseases; the General Clinical Research Center; The Heart Institute; the Childrens Orthopaedic Center; and the USC-CHLA Institute for Pediatric Clinical Research.
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