Heredity has long been known to play an important role in determining who will get osteoporosis, the bone-thinning disease that afflicts some 20 million Americans and results in costly, debilitating and sometimes life-threatening fractures in older women and, to a lesser extent, men.
Now, in what has been called the most important finding in the field in a decade, an Australian research team has shown that a single gene is the main hereditary culprit, accounting for about one-third of a person’s overall risk of developing osteoporosis.
The gene, the team showed, has a major influence on how dense a person’s bones become by early adulthood, after which bone loss slowly begins to overwhelm bone growth. The denser a person’s bones are in early adulthood, the less likely it is that they will eventually become thin enough to break readily.
The finding could lead to a simple test given in childhood to identify those who will be most prone to osteoporosis later in life.
According to the report by Dr. John Eisman and colleagues in Thursday’s issue of the journal Nature, people with the gene dubbed b have higher bone density than those with its genetic counterpart B.
Those with two b genes, one from each parent, have the densest bones, and those with two B genes have the least dense bones. Those with one of each, the Bb genotype, have bones of intermediate density.
In one study, the researchers calculated that having the BB combination could make an older woman four times more likely to sustain a hip fracture than she would be if she had the bb combination.
In commenting on the finding, Dr. Gregory Mundy, an endocrinologist at the University of Texas in San Antonio, said, “People have been studying the genetic influence on osteoporosis for 20 years. This is the first time a specific gene has been linked to the disorder, and it’s a major step in sorting out the hereditary influence on bone mass.”
The researchers said the b gene provides the blueprint for protein receptors that bind with vitamin D hormone. This hormone, the active form of vitamin D, is crucial to determining how well the body uses calcium to build new bone. Without a proper hookup between the receptors and the hormone, vitamin D cannot optimally promote bone growth.
In an interview, Mundy said, “If further studies show that the new finding is right and if the receptor for vitamin D can be manipulated, say, by giving extra vitamin D, it would help to increase bone mass in people susceptible to osteoporosis and prevent it from occurring.”
Dr. B. Lawrence Riggs, an endocrinologist specializing in osteoporosis at the Mayo Clinic in Rochester, Minn., suggested a different preventive approach: Identifying children with a genetic susceptibility to osteoporosis and then encouraging them to consume adequate amounts of calcium and appropriate amounts of protein.
He also said that as those children get older, they should refrain from smoking and should get regular physical exercise like running and cycling, which use the muscles attached to the long bones of the body.
Riggs said identification of the vitamin D receptor gene “is probably the single most important discovery in osteoporosis in the last decade.”
About half of a person’s risk of developing the bone-thinning disorder stems from “not having enough bone to start with,” he said, adding that about 15 percent of the population has the most unfavorable gene combination, the BB genotype.
