Study Finds Link Between Rare Genetic Mutation and Osteoporosis

Oct. 8, 2015

An international genetic study published recently in the journal Nature found that rare mutations, which occur in less than five percent of a population, might partially cause common diseases like osteoporosis. This finding challenges a popular belief that all individuals who have a disease must also have the same genetic reasons for having that disease.

“Our findings suggest that common complex disease is actually a collection of a whole bunch of events or genetic changes,” says Cheryl Ackert-Bicknell, Ph.D., professor of Orthopedics in the Center for Musculoskeletal Research at the University of Rochester School of Medicine and Dentistry and an author of the study. “It’s not one osteoporosis. It’s not one cardiovascular disease. It’s not one breast cancer.”

Vitruvian man with DNA helix

Brent Richards, Ph.D. of the Lady Davis Institute at the Jewish General Hospital at McGill University led the study, which analyzed genetic material from an extremely large group of people of European descent. Results showed that two rare genetic mutations near the gene for EN1, a protein that is important in mouse limb development, were linked to increased bone mineral density and decreased risk of fracture. This suggests that the genetic change in EN1 decreases the risk for osteoporosis.

Ackert-Bicknell, one of several lead authors of the study, went beyond the statistics to test whether EN1 truly caused a change in bone mineral density in animals. Her team at the University of Rochester discovered that EN1 was turned on in the cells that make bone, but not in the cells that resorb or destroy bone.

In addition, as part of this study, the research team turned off EN1 expression in mice, which led to very high numbers of bone destroying cells and low bone mass in the animals. Researchers speculate that EN1 is normally expressed in the bone building cells and plays some role in communicating with bone destroying cells to help balance the constant breakdown and repair of bone.

“Bone is a complicated organ,” says Ackert-Bicknell. “It’s not an inert, dead tissue. It’s constantly made and constantly destroyed. The skeleton you woke up with today is not the same skeleton you will wake up with tomorrow. We think EN1 promotes discussion between bone builders and bone destroyers.”

Ackert-Bicknell’s work solidifies the link between EN1 and osteoporosis traits in living animals, which further supports the idea that rare mutations may cause common diseases.

“There may be 100 different types of osteoporosis,” say Ackert-Bicknell, each with a distinct constellation of genetic causes. “This means we may need several different ways to treat these diseases and taking a personalized medicine approach may be the key to preventing or thwarting common diseases.”

But, Ackert-Bicknell cautions, “This study isn’t going to change practice in the clinic tomorrow.” She plans to continue investigating how these rare mutations control EN1 expression and bone mass.

To access the original study, click here.


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