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A new "atlas" of genetic impact on osteoporosis



There is a normal bone on the left side and an osteoporotic bone on the right. Credit: International Osteoporosis Foundation

A breakthrough new study conducted by scientists from the Lady Davis Institute (LDI) at the Jewish General Hospital (JGH) has been able to develop an atlas of genetic factors associated with estimated bone mineral density (BMD), one of the most clinically relevant factors in diagnosing osteoporosis. Article published in Genetics of nature, identifies 518 genomic loci, of which 301 are newly discovered, which explain 20% of the genetic variability associated with osteoporosis. After identifying so many genetic factors, it offers a great opportunity to develop new targeted drugs to treat the disease and reduce the risk of fractures.

'Our findings represent a significant advance in highlighting the potential for drug development,' explained Dr Brent Richards, lead investigator, geneticist at the LDI Clinical Epidemiology Center, who is treating patients with osteoporosis in their JGH practice. 'This set of genetic changes that affect BMD provides targeted drugs that can be helpful in preventing osteoporotic fractures.'

Osteoporosis is a very common condition associated with age, characterized by progressive reduction of bone strength, which causes a high risk of fracture. Particularly in older patients, fractures can have serious consequences, including the risk of death. Among all patients, fractures are associated with high burdens related to hospitalization and prolonged rehabilitation. With the aging of the population, the urgency to improve preventive measures is becoming more and more intense.

"We currently have few treatment options," said Dr. Richards, professor of medicine, human genetics, and epidemiology and biostatistics at McGill University, "and many patients at high risk for fractures do not currently take drugs for fear of side effects. Although it is always better to prevent rather than cure, we can prescribe preparations for injections that build bones, but they are definitely too expensive. We have drugs that prevent bone loss, but they have to be taken according to a strict schedule, resulting in a number of people who should be treated but they are gone, it's high, so we think we'll be more successful when it comes to encouraging patients to follow a treatment schedule when it can be simplified. "

It was the largest study undertaken so far on genetic determinants of osteoporosis, assessing over 426,000 people in the British biobank. After analyzing the data, the researchers improved their findings to isolate a set of genes that are very heavily enriched with known target drugs. This smaller set of target genes will allow drug makers to narrow down the search for a clinical solution to the problem of preventing fractures in people predisposed to osteoporotic fractures. Animal models have already proved the validity of some of these genes.

"Although we have found many genetic factors associated with BMD, the type of precise medicine genetics offers, should allow us to improve those factors that can have the greatest impact on bone density improvement and reduce the risk of fractures," said Dr. John Morris, also from LDI and McGill University, lead author of the research.


Browse further:
Cataracts associated with a higher risk of osteoporosis and fractures

More information:
Atlas of genetic influences on osteoporosis in humans and mice, Genetics of nature (2018). DOI: 10.1038 / s41588-018-0302-x, https://www.nature.com/articles/s41588-018-0302-x

Journal reference number:
Genetics of nature

Delivered by:
McGill University


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