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New "atlas" of genetic effects on osteoporosis

Left normal bone and right osteoporotic bone. Credit: International Osteoporosis Foundation

A pioneering new study by researchers from the Lady Davis Institute (LDI) at the Jewish General Hospital (JGH) allowed us to collect an atlas of genetic factors related to bone mineral density (BMD), one of the most clinically significant factors in diagnosing osteoporosis. Article published in Nature geneticsidentifies 518 loci of the entire genome, of which 301 are recently discovered, which account for 20% of the genetic dispersion associated with osteoporosis. Having identified so many genetic factors, one can hope for the development of a new target therapy for treating the disease and reducing the risk of fractures.

“Our results represent significant progress in highlighting drug development opportunities,” explains Dr. Brent Richards, lead researcher, geneticist at the Clinical Epidemiology Center of LDI, who treats patients with osteoporosis in his practice at JGH. "This set of genetic changes that affect the IPC gives drug targets that are likely to be useful for the prevention of an osteoporotic fracture."

Osteoporosis is a very common age condition characterized by a gradual decrease in bone strength, which leads to a high risk of fractures. Especially in older patients, fractures can have serious consequences, including the risk of mortality. Among all patients, fractures impose the brunt of hospitalization and long-term rehabilitation. As the population ages, the need to improve preventive measures becomes more acute.

“We currently have few treatment options,” said Dr. Richards, a professor of medicine, human genetics, epidemiology and biostatistics at McGill University, “and many patients with a high risk of fractures do not take modern medicines because of the fear of side effects. Despite the fact that it is always better to prevent than to cure. We can prescribe injectable drugs that build bones, but they are prohibitively expensive. We have drugs that prevent bone loss, but they need to be taken on a strict schedule. As a result, the number of people who should be treated, but who are not, is large. Therefore, we believe that we will have more success in forcing patients to comply with the treatment when it can be simplified. ”

This was the largest ever study of the genetic determinants of osteoporosis, in which more than 426,000 people in the British biobank participated. After analyzing the data, the researchers further refined their findings in order to isolate a set of genes that are highly enriched for known target drugs. This smaller set of target genes will allow drug developers to narrow their search for a solution to the clinical problem of preventing fractures in people who are prone to osteoporotic fractures. Animal models have already proven the validity of some of these genes.

“Despite the fact that we discovered a lot of genetic factors related to BMD, the types of exact drugs that genetics offer should allow us to hone those factors that can have the greatest impact on improving bone density and reducing the risk of fractures,” said Dr. John . Morris, also from LDI and McGill University, lead author of the study.

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Additional Information:
Atlas of genetic effects on osteoporosis in humans and mice, Nature genetics (2018). DOI: 10.1038 / s41588-018-0302-x,

Link to the magazine:
Nature genetics

Provided by:
McGill University

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