Scientists have compiled an atlas of the many genetic influences on osteoporosis. The researchers, from the Lady Davis Institute (LDI) at the Jewish General Hospital (JGH), identified 518 loci in the human genome, 301 of which are newly found, which can explain twenty percent of the genetic variation in osteoporosis. This wide array of genetic factors can give investigators clues to how good therapeutics will work and potentially could lead to better preventative treatments for fractures. The findings have been reported in Nature Genetics.
"Our findings represent significant progress in highlighting drug development opportunities," said the lead investigator of the work Dr. Brent Richards, a geneticist at the LDI's Centre for Clinical Epidemiology who sees osteoporosis patients in his practice at the JGH. "This set of genetic changes that influence BMD provides drug targets that are likely to be helpful for osteoporotic fracture prevention."
Our bones are continually renewing themselves, but as we age the body is not as efficient at making new bone. That can lead to a reduction in the mass of bones, which impacts whether or not a person develops osteoporosis. Naturally, osteoporosis becomes more common as people get older; the bones become brittle and weak and are at high risk of fracture. Many people don't even know they have it until they break a bone, which can cause an increased risk of death. It impacts people of both sexes and all races but is most common in white and Asian women who are post-menopausal.
"We currently have few treatment options and many patients who are at high risk of fractures do not take current medications because of fear of side effects. Notwithstanding that it is always better to prevent than to treat,” said Dr. Richards, a Professor of Medicine, Human Genetics, and Epidemiology and Biostatistics at McGill University
“We can prescribe injectables that build bone, but they are prohibitively expensive. We have medications that prevent loss of bone, but they must be taken on a strict schedule. As a result, the number of people who should be treated, but are not, is high. Therefore, we believe that we will have greater success in getting patients to follow a treatment regimen when it can be simplified,” he added.
This study assessed genetic data from over 426,000 people, which is stored in the UK Biobank. The analysis allowed the researchers to narrow down their findings to focus on known drug targets. That will help drug developers to create a clinical therapeutic for osteoporosis sufferers, to prevent fractures in those who are predisposed.
"Although we found many genetic factors associated with BMD, the kind of precision medicine that genetics offers should allow us to hone in on those factors that can have the greatest effect on improving bone density and lessening the risk of fracture," said the lead author of the work, Dr. John Morris, also from the LDI and McGill University.
For many years, Richards has been working on the genetics of osteoporosis. In the video above from several years ago, he briefly describes the discovery of an osteoporosis-related gene. The video below is a more lengthy talk in which he discusses the genetics of the disorder.