May 2019Research at the Lady Davis Institute

New “atlas” demonstrates genetic influences on osteoporosis

A ground-breaking new study has succeeded in compiling an “atlas” of genetic factors that are associated with estimated bone mineral density, one of the most clinically relevant factors in diagnosing osteoporosis.

The identification of so many genetic factors holds great promise for developing novel targeted therapeutics to treat the disease and reduce the risk of fracture.

Published in Nature Genetics, the study identifies 518 genome-wide loci, of which 301 are newly discovered and explain 20 per cent of the genetic variance associated with osteoporosis.

“Our findings represent significant progress in highlighting drug development opportunities,” explains Dr. Brent Richards, the lead investigator, who is a geneticist at the Lady Davis Institute (LDI) and treats patients with osteoporosis in his practice at the JGH.

“This set of genetic changes which influence bone mineral density provides drug targets that are likely to be helpful for osteoporotic fracture prevention.”

Osteoporosis is a very common age-related condition that is characterized by a progressive reduction of bone strength, resulting in a high risk of fracture. Especially among older patients, fractures can have severe consequences, including the risk of mortality.

Among all sufferers, fractures pose major burdens of hospitalization and extended rehabilitation. As the population ages, the urgency of improving preventive measures becomes all the more intense.

“We currently have few treatment options,” says Dr. Richards, “and many patients who are at high risk of fractures do not take current medications because of the fear of side effects. Even so, it is always better to prevent than to treat.

“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 we will have greater success in getting patients to follow a treatment regimen when it can be simplified.”

This was the largest study ever undertaken of the genetic determinants of osteoporosis, involving an assessment of more than 426,000 individuals in the UK Biobank. After analyzing the data, the researchers further refined their findings to isolate a set of genes that are very strongly enriched for known drug targets.

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 those people who are predisposed to osteoporotic fractures.

LDI researcher receives major genetics award

Dr. John Morris

Dr. John Morris of the Lady Davis Institute, who recently completed his Ph.D. studies in McGill’s Department of Human Genetics, was among the recipients the 2018 Charles J. Epstein Trainee Award for Excellence in Human Genetics Research from the American Society of Human Genetics.

The award was conferred on the strength of research that resulted in the development of a genetic “atlas” of osteoporosis. Compared to previous studies, the “atlas” more than doubles the number of associated loci of bone mineral density, while increasing to 20 per cent the variance that is explained by genetic factors.

Animal models have already proven the validity of some of these genes.

“Although we found many genetic factors associated with bone mineral density, the kind of precision medicine that genetics offers should allow us to home in on factors that can have the greatest effect on improving bone density and lessening the risk of fracture,” adds Dr. John Morris, of the LDI and McGill University, who is the first author of the study.

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