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HSL Scientists Contribute to Gene Study That Could Aid in Osteoporosis Detection

A consortium of researchers, including scientists at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research, has identified common variations of genes that are associated with both bone mineral density (BMD) and fracture risk. The findings may help clinicians predict who is at risk for osteoporosis-related fractures and may help in the development of new anti-osteoporosis drugs.

In the March 19 issue of the Journal of the American Medical Association, the researchers discovered two variations in the low-density lipoprotein receptor-related protein (LRP5) gene and the LRP6 gene that are strongly associated with bone mineral density.  Mutations in LRP5 gene cause rare syndromes characterized by altered bone mineral density. More common LRP5 variants may affect osteoporosis risk in the general population.

Mutations to the gene also have been implicated in bone mass disorders and osteoporosis-pseudoglioma syndrome, which is characterized by severe osteoporosis and blindness. An inherited mutation in LRP6 is linked low trauma fractures and low BMD, as well as increased fracture risk in elderly men.

The researchers, part of GENOMOS, a European Union-funded consortium of scientists seeking to identify genetic factors for osteoporosis, examined BMD data from more than 37,500 individuals in the U.S. and Europe. BMD of the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry and fractures were documented either by radiographic records, hospital data, or patient questionnaires.

The two LRP5 gene variations had highly significant effects on bone mineral density in the lumbar (lower) spine and femoral neck. The magnitude of the effects was small, the researchers say, but consistent across studies. Fractures of the femoral neck, where the ball of the ball-and-socket hip joint is broken off, are common hip fractures.

“Although the magnitude of the effect was modest,” says Dr. Kiel, “the effect was very consistent in different populations and independent of gender or age. This suggests a role for LRP5 in determining BMD and fracture risk throughout life in the general population.”

Dr. Kiel and David Karasik, Ph.D., an Marcus Institute scientist who contributed to the study, say that a single marker such as these mutations explains only a small portion of osteoporosis risk, but that the identification of several such risk variants may eventually help improve clinical prediction of who might suffer osteoporosis-related fractures. They say that the LRP5 variant may also offer “ insights about mechanisms and pathways that may be useful in drug development.”