Nav: Home

Osteoporosis, fracture risk predicted with Stanford-developed genetic screen

July 26, 2018

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 percent 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 percent 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.

Early identification of people with an increased genetic risk for osteoporosis could be an important way to prevent or reduce the incidence of bone fracture, which according to the National Osteoporosis Foundation affects 2 million people each year and accounts for $19 billion in annual health care costs.

"There are lots of ways to reduce the risk of a stress fracture, including vitamin D, calcium and weight-bearing exercise," said Stuart Kim, PhD, an emeritus professor of developmental biology. "But currently there is no protocol to predict in one's 20s or 30s who is likely to be at higher risk, and who should pursue these interventions before any sign of bone weakening. A test like this could be an important clinical tool."

Kim is the sole author of the study, which will be published online July 26 in PLOS ONE.

Low bone-mineral density as 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 amount 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 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.

Using the algorithm, Kim was able to identify 1,362 independent differences, or single-nucleotide polymorphisms, that correlated with low bone-mineral density readings. He then used a machine-learning method called LASSO, developed in 1996 by Stanford professor of biomedical data science and of statistics Robert Tibshirani, PhD, to further hone the data.

The resulting algorithm assigned a score to each of the nearly 400,000 participants to indicate their risk of low bone-mineral density; subsequent analyses showed that those in the bottom 2.2 percent of these scores were 17 times more likely than their peers to have been diagnosed with osteoporosis and nearly twice as likely to have experienced a bone fracture.

"The analysis worked really well," Kim said. "This is one of the largest genomewide association studies ever completed for osteoporosis, and it clearly shows the genetic architecture that underlies this important public health problem."

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'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."
-end-
The study is an example of Stanford Medicine's focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

The research was supported by the National Institute on Aging (grant AG02594110).

Stanford's Department of Developmental Biology also supported the work.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med.stanford.edu/school.html. The medical school is part of Stanford Medicine, which includes Stanford Health Care and Lucile Packard Children's Hospital Stanford. For information about all three, please visit http://med.stanford.edu.

Stanford Medicine

Related Osteoporosis Articles:

Mind the (osteoporosis treatment) gap!
A new review, referencing key clinical studies, guidelines and audits, outlines the main global challenges (and their solutions) facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health and fracture prevention.
Outwitting the 'silent thief' of osteoporosis
In a world first, new Australian research has revealed that genetic profiling can help predict whether an individual will break a bone through osteoporosis.
Osteoporosis: Antibody crystallized
Inhibiting a protein called Sclerostin could probably help treating the bone-loss disease osteoporosis.
JBMR perspective: A crisis in the treatment of osteoporosis
The remarkable progress made over the past 30 years to reduce fractures and dramatically improve the quality of life for millions of osteoporosis patients is rapidly being reversed, say two bone health experts in a Journal of Bone and Mineral Research article published online today.
The developmental origins of osteoporosis
Osteoporosis may have its origins in early life, but the consequences are not apparent until late adult life.
Task force provides guidance on use of osteoporosis drugs
A new report by a task force of the American Society for Bone and Mineral Research provides guidance on the use of bisphosphonates, which are the most commonly used medications for osteoporosis.
Whole genome-sequencing uncovers new genetic cause for osteoporosis
Using one of the world's most extensive genetics data sets, an international research team led by Dr.
Men far less likely to prevent, screen for osteoporosis
While the consequences of osteoporosis are worse in men than women -- including death -- older males are far less likely to take preventive measures against the potentially devastating bone-thinning disease or accept recommendations for screening, according to startling new research by North Shore-LIJ Health System geriatricians.
'Aquatic osteoporosis' jellifying lakes
North American lakes are suffering from declining calcium levels, says new research from Queen's University.
Osteoporosis, not just a woman's disease
While osteoporosis prevention and treatment efforts have historically been focused on post-menopausal women, a new study from Beth Israel Deaconess Medical Center suggests that critical opportunities are being lost by not focusing more attention on bone loss and fracture risk in older men.

Related Osteoporosis Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".