Researcher Says Genetic Screenings Can Discover Osteoporosis Risk

The largest genomewide association studies ever completed for osteoporosis identified 899 loci, or regions, in the human genome associated with low bone mineral density (BMD), 613 of which have not yet been discovered.

The Stanford University School of Medicine researcher who made the finding said that widespread genetic screenings could predict a person's future risk of osteoporosis and bone fracture. The study was published online in PLoS One.

Stuart K. Kim, PhD, an emeritus professsor of developmental biology and a geneticist, said in a statement that he started his research as a way to help elite athletes or members of the military learn if they are at risk of bone injury during training. When the results showed a strong correlation between people predicted to have the highest risk of low BMD and the development of osteoporosis and fracture, he expanded the research.

In an interview with The American Journal of Managed Care^®, Kim said that the screening test could be implemented as soon as clinical trials take place and that he is also hoping that managed healthcare companies consider the test. According to him, identifying people at risk when they are younger, before a fall or fracture, could help cut down on healthcare costs related to osteoporosis—about $19 billion annually, according to the National Osteoporosis Foundation.

Identifying people at risk when they are younger would give them more time to intervene with weight-bearing exercises or other methods, he said.

Osteoporosis is responsible for as many as 1 in 2 fractures in women and 1 in 4 in men over the age of 50 years. But many people will not know they have osteoporosis, a skeletal disorder characterized by loss of bone mass, deterioration of bone tissue, and decline in bone quality, until they have a fracture. In some cases, fractures can lead to disability, chronic pain, loss of independence, lower quality of life, and even death. About 21% to 30% of patients who experience a hip fracture die within 1 year.

BMD tests are usually only performed on people with a family history of osteoporosis or those who have experienced a recent fracture from a fall. Last month, the United States Preventive Services Task Force updated its 2011 recommendation about osteoporosis screening, recommending that women over the age of 65 years continue to get screened and issuing new information about how clinicians should use screening tools to evaluate women younger than 65 years at high risk for developing the bone disease.

"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."

Kim analyzed the genetic data and health information of nearly 400,000 people in the UK Biobank, a database of deidentified information. He collected data on each participant’s BMD, age, height, weight, and sex, as well as each person’s genome sequence.

He then developed and trained a computer algorithm to identify naturally occurring genetic differences among people found to have low BMD. He was able to identify 1362 single nucleotide polymorphisms, frequently called SNPs, that correlated with BMD readings.

The resulting algorithm assigned a score to each of the nearly 400,000 participants to indicate their risk of low BMD. Subsequent analyses showed that about 2% had the highest risk and were 17 times more likely to have been diagnosed with osteoporosis and nearly twice as likely to have experienced a bone fracture.

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 BMD with preventive measures. He's 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."

Kim compared the test to the screening test for the BRCA2 gene, where about 0.2% of women tested will have a cancer-associated mutation that increases their risk of breast cancer to about 6 times that of a woman without a BRCA2 mutation.

One limitation of the study is that the UK database is composed primarily of people with a European background. Kim said his algorithm works "pretty well" on African Americans and Asians, but he would need a larger, diverse dataset in order to retrain the algorithm to work as well as the first one.

Reference

Kim SK. Identification of 613 new loci associated with heel bone mineral density and a polygenic risk score for bone mineral density, osteoporosis and fracture [published online July 26, 2018]. PLoS One. 2018;13(7):e0200785. doi: 10.1371/journal.pone.0200785.