A new genetic screen may predict a person's future risk of osteoporosis and bone fracture, according to a study by a researcher at the Stanford University School of Medicine
Specifically, the study, one of the largest of its kind, identified 899 regions in the human genome associated with low bone mineral density, 613 of which have never before been identified.
People deemed to be at high risk—about 2% of those tested—were about 17 times more likely than others to develop osteoporosis and about twice as likely to experience a bone fracture in their lifetimes. In comparison, about 0.2% of women tested will have a cancer-associated mutation in the BRCA2 gene, which increases their risk of breast cancer to about six times that of a woman without a BRCA2 mutation.
Low bone mineral density as the predictor
Kim originally approached his investigation as a way to help elite athletes or members of the military learn if they are at risk of bone injury during strenuous training. Once he had compiled the results, however, he saw a strong correlation between people predicted to have the highest risk of low bone mineral density and the development of osteoporosis and fracture.
Osteoporosis, or porous bone, is a disease that results in a reduction in bone mass due to bone loss or defects in bone production, or both. It's correlated with a high incidence of bone fracture because the weakened bone is less able to withstand the stress of slips and falls, or sometimes even normal daily activity. It affects millions of Americans and is responsible for as many as 1 in 2 fractures in women and 1 in 4 in men over the age of 50.
Two previous studies have shown that there is a genetic component to osteoporosis; you're more likely to develop it if you have a family history of the condition.
In addition to genetics, your behaviors, including the frequency and type of exercise you prefer and your diet, as well as your weight and gender, also play a large role in bone health. Recently, genetic studies on large groups of individuals have shown that hundreds of genes are likely involved, each making its own small contribution to either increased or decreased risk of the disease.
Osteoporosis is often diagnosed with a bone mineral density test that uses X-rays to measure the number of minerals, such as calcium, in a person's hip, spine or heel. But bone-mineral density tests are usually only performed on people with a family history of osteoporosis or those who have experienced a recent fracture from a simple fall.
"The most common clinical algorithm used to detect or predict osteoporosis is called FRAX," Kim said. "But the catch is that the two largest components of the FRAX algorithm are bone-mineral density and prior fracture. So it's kind of a circular argument."
Developing an algorithm
Kim analyzed the genetic data and health information of nearly 400,000 people in the UK Biobank—a vast compendium of de-identified information freely available to public health researchers around the world.
For each participant, Kim collected data on bone-mineral density, age, height, weight, and sex, as well as that participant's genome sequence. He then developed a computer algorithm to identify naturally occurring genetic differences among people found with low bone-mineral density.
Kim is now planning to arrange a clinical trial to investigate whether elite athletes and select members of the military identified by the algorithm as being at high risk for osteoporosis and potential fracture can increase their bone-mineral density with simple preventive measures. He is also interested in conducting a similar study among younger people with no obvious clinical symptoms of bone weakening.
"Fifteen million people in this country have already accessed their genome sequences using direct-to-consumer testing services," Kim said. "I think this analysis has the potential to become the standard of care in the coming years. It would be a relatively simple measure to identify those who should have their bone mineral density tested and perhaps take steps at an early age to ensure their future bone health."