Vibration Research
Low Buzz May Give Mice Better Bones and Less Fat
By GINA KOLATA
Published: October 30, 2007
Clinton T. Rubin knows full well that his recent results are surprising — that no one has been more taken aback than he!
Less Fat in Vibrated Mice
And no wonder, other scientists say. Dr. Rubin, director of the Center for Biotechnology at the State University of New York at Stony Brook, is reporting that in mice, a simple treatment that does not involve drugs appears to be directing cells to turn into bone instead of fat.
All he does is put mice on a platform that buzzes at such a low frequency that some people cannot even feel it. The mice stand there for 15 minutes a day, five days a week. Afterward, they have 27 percent less fat than mice that did not stand on the platform — and correspondingly more bone.
“I was the biggest skeptic in the world,” Dr. Rubin said. “And I sit here and say, ‘This can’t possibly be happening.’ ‘Wow, this is really cool!’
The mice are less fat after standing on the platform, researchers say, — that fat precursor cells are turning into bone.
Even so, the National Institutes of Health is sufficiently intrigued to investigate the effect in a large clinical trial in elderly people, said Joan A. McGowan, a division director at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Dr. McGowan notes that Dr. Rubin is a respected scientist and that her institute has helped pay for his research for the past 20 years.
“I’d call it provocative,” she said of the new result. “It says, ‘Keep looking here; this is exciting. “it is a fundamental scientific finding.”
The story of the finding, which was published online and will appear in the Nov. 6 issue of Proceedings of the National Academy of Sciences, began in 1981 when Dr. Rubin and his colleagues started asking why bone is lost in aging and inactivity.
“Bone is notorious for ‘use it or lose it,’” Dr. Rubin said. “Astronauts lose 2 percent of their bone a month. People lose 2 percent a decade after age 35. Then you look at the other side of the equation. Professional tennis players have 35 percent more bone in their playing arm. What is it about mechanical signals that makes Roger Federer’s arm so big?”
At first, he assumed that the exercise effect came from a forceful impact — the pounding on the leg bones as a runner’s feet hit the ground or the blow to the bones in a tennis player’s arm with every strike of the ball. But Dr. Rubin was trained as a biomechanical engineer, and that led him to consider other possibilities. Large signals can actually be counterproductive, he said, adding: “If I scream at you over the phone, you don’t hear me better. If I shine a bright light in your eyes, you don’t see better.”
Over the years, he and his colleagues discovered that high-magnitude signals, like the ones created by the impact as foot hits pavement, were not the predominant signals affecting bone. Instead, bone responded to signals that were high in frequency but low in magnitude, more like a buzzing than a pounding.
That makes sense, he went on, because muscles quiver when they contract, and that quivering is the predominant signal to bones. It occurs when people stand still, for example, and their muscles contract to keep them upright. As people age, they lose many of those postural muscles, making them less able to balance, more apt to fall and, perhaps, prone to loss of bone.
“Bone is bombarded with little, teeny signals from muscle contractions,” Dr. Rubin said.
He discovered that in mice, sheep and turkeys, at least, standing on a flat vibrating plate led to bone growth. Small studies in humans — children with cerebral palsy who could not move much on their own and young women with low bone density — indicated that the vibrations would build bone in people, too.
Some answers may come from the federal clinical trial, which will include 200 elderly people in assisted living. It is being directed by Dr. Douglas P. Kiel, an osteoporosis researcher and director of medical research at the Institute for Aging Research at Harvard. The animal work made him hopeful that the buzzing platforms would have an effect on human bones.“This work is fascinating and very legitimate,” Dr. Kiel said.
Dr. Rubin says he decided to look at whether vibrations affect fat because he knows what happens with age: bone marrow fills with fat. In osteoporosis, the bones do not merely thin; their texture becomes lacy, and inside the holes is fat. And a few years ago, scientists discovered a stem cell in bone marrow that can turn into either fat or bone, depending on what signal it receives.
No one knows why the fat is in bone marrow — maybe it provides energy for failing bone cells, suggests Dr. Clifford J. Rosen, director of the Maine Center for Osteoporosis Research and Education. And no one knows whether human fat cells ever leave the bone marrow and take up residence elsewhere.
But Dr. Rubin had an idea. “We thought, Wait a second,” he said. “If we are mechanically stimulating cells to form bone, what isn’t happening? We thought maybe these bone progenitor cells are driving down a decision path. Maybe they are not becoming fat cells.”
He paid a visit to Jeffrey E. Pessin, a diabetes expert at Stony Brook, and presented his hypothesis. Dr. Pessin laughed uproariously. He “almost kicked me out of his office,” as Dr. Rubin put it.
But when Dr. Rubin decided to go ahead anyway, Dr. Pessin joined in. Their hope was to see a small effect on body fat after the mice stood on the platforms 15 minutes a day, 5 days a week, for 15 weeks. Dr. Rubin was stunned by the 27 percent reduction.“Talk about your jaw dropping,” he said. “It is a very intriguing paper,” said Claude Bouchard, an obesity researcher who is director of the Pennington Center for Biomedical Research at Louisiana State University. But he wondered whether the mice on the platform were simply burning more calories.
“It seems to me,” Dr. Bouchard said, “that putting myself in the body of a mouse, if I was on a platform that was vibrating 90 times a minute, I would try to adhere to the surface and not be thrown off. I would probably tense my legs a little bit. That is energy expenditure.”
Dr. Rudolph L. Leibel, an obesity researcher who is co-director of the Naomi Berrie Diabetes Center at Columbia University, had similar questions. If the mice that stood on the platform became thinner and if they ate as much as mice that did not stand on the platform (as Dr. Rubin reported), they must be burning more calories, Dr. Leibel said. “This is very, very cool,” said Dr. John B. Buse, a diabetes researcher at the University of North Carolina who is president for science and medicine at the American Diabetes Association. If it turned out to hold for people too, “it would be great for diabetes,” he added. He noted that people with Type 2 diabetes were likely not only to be overweight but also to have problems with their bones. “It is almost too good to be true,” he said.