California Pacific Currents 2001
Is the Hip Bone Connected to the Heart? Warren Browner Continues the Search for Links between Bone Metabolism and Heart Health
Warren S. Browner, MD, MPH
Call it leadership by example. Call it an abiding passion for research. Or maybe it's simply force of habit. But if anyone thought that Warren S. Browner, MD, MPH, was going to hang up his well-worn researcher's hat when he became the scientific director for the California Pacific Medical Center Research Institute and vice president, academic affairs, for California Pacific Medical Center, they better think again. Although the administrative responsibilities of his position certainly require a full measure of attention, Dr. Browner insists on carving out about 20 percent of his time to continue his pursuit of research in clinical epidemiology.
A Message in the Bone
In his current projects, Dr. Browner and his worldwide network of collaborators are extending their decade-long exploration of the connections between bone metabolism and general health in women. “Our original work showed that women who had low bone density or osteoporosis were more likely to die from a variety of causes for reasons that we didn't—and still don't—fully understand,” explains Dr. Browner. His group's work from the early and mid-1990s uncovered surprising correlations between low bone density and coronary artery disease, pulmonary disease, breast cancer, and other conditions.
“Originally,” he recalls, “the concept was that the bones are a sort of tablet upon which one's life history is written…and that fundamental aspects of health, such as hormone levels, affect the bones. Therefore, they can be a useful marker for overall health.”
In deciphering the possible medical meaning in the bone structure, Dr. Browner's group was also trying to determine if estrogen might act as a kind of biological scribe in this process— perhaps building up the bone structure and leading to better health when present in adequate amounts. “Over time the story has become much more complicated and fascinating,” says Dr. Browner.
When Two Tribes Meet
The twist in the story came when, just as the Browner team was describing these bone-heart connections in people, several groups of laboratory investigators found that the biomolecular process that regulates the calcification of bones is also involved in calcification of other body parts—such as blood vessels.
Two tribes of researchers, taking entirely different paths through the forest, had stumbled across the same discovery. “Two different ways of looking at the world were coming to similar conclusions,” explains Dr. Browner.
The epidemiologists and cell scientists are now sharing their notebooks and several joint expeditions are underway. For example, laboratories in university, government, and corporate settings have discovered a specific substance (called osteoprotegerin by one of the discoverers) that regulates bone formation. When mice fail to make adequate quantities of this molecular messenger, their bones fail to calcify, but their blood vessels do.
Pursuing this lead from his fellow researchers, Dr. Browner recently participated in a large study that retrieved stored blood samples and checked the serum levels of osteopro-tegerin in women. They found that those women with the highest concentrations of the key molecule were more likely to die of cardiovascular disease than women with lower concentrations. Women with high levels of osteoprotegerin were also prone to have diabetes, which is often associated with calcification of blood vessels. “The whole picture is starting to come together,” says Dr. Browner.
The Next Step
The next phase of Dr. Browner's clinical research will involve not only measurement of osteoprotegerin but also use sophisticated imaging techniques to measure the level of calcium in the blood vessels and bone. The actual test for coronary calcification, called electron beam computerized tomography (familiar to many Bay Area residents as “the Heartscan test”) will allow the researchers to figure out the true role of arterial calcium in coronary disease.
“If you have calcium in your coronary artery, that's probably not a good thing,” says Dr. Browner. “But we don't know for sure. One of the questions I'm asking is if calcium in an artery stabilizes an atherosclerotic plaque, or if the calcium makes it more brittle and likely to cause problems. Beyond that, if we find that calcification is protective, then we will look for therapies to encourage calcification. If we find that calcium makes plaque more brittle, we'll go in the opposite direction.”
The clinical implications of this line of work are clear. And although results are still years away, the potential for better prevention of cardiovascular disease in millions of Americans makes the continuation of Dr. Browner's research vital. Fortunately, these important international efforts and Dr. Browner himself have found an environment at the Research Institute that is conducive to such ongoing research.