Spotlight on Research 2010

May 2010 (historical)

Researchers Identify Genetic Variations Associated with Low Bone Mass

Scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) working with an international research consortium have identified 20 genetic variations associated with the development of osteoporosis, a condition in which bones lose mass to the point that they are at increased risk of fracture.

Knowing that genetic factors account for a substantial proportion of the variance in bone mass, the scientists set out to learn more about the genes involved using genome-wide association studies. The studies allowed them to test whether particular genetic variations, referred to as single nucleotide polymorphisms (SNPs), were more common in people with low bone mass density than without. Combining the information on bone mass density and more than 2.5 million SNPs from more than 19,000 people led them to the 20 variations, only seven of which had been detected in previous studies.

The consortium used data from the Framingham Osteoporosis Study, funded by grants from the NIAMS, the National Institute on Aging and the National Heart, Lung, and Blood Institute. Investigator David Karasik, Ph.D., says the researchers don't yet know what specifically the genes do, but ongoing research into the function of bone mass genes should find clues. The second stage of the consortium's work, he says, will be to almost double the sample size to more than 32,000, which should enable the researchers to find more genetic variations and help confirm the role of some of the already-discovered SNPs.

Karasik sees potential implications of this research, including a better understanding of the mechanisms of bone loss and osteoporosis risk, which could lead to the development of better pharmaceuticals to treat it.

By being able to identify who's at greatest risk of osteoporosis – and why – he says doctors may eventually be able to target treatments to build stronger bones and stave off bone loss before it happens.

The findings were published in the journal Nature Genetics.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at

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Reference: Rivadeneira F, Styrkársdottir U, Estrada K, Halldórsson B, Hsu Y, Richards J, Zillikens M, Kavvoura F, Amin N, Aulchenko Y, Cupples L, Deloukas P, Demissie S, Grundberg E, Hofman A, Kong A, Karasik D, van Meurs J, Oostra B, Pastinen T, Pols H, Sigurdsson G, Soranzo N, Thorleifsson G, Thorsteinsdottir U, Williams F, Wilson S, Zhou Y, Ralston S, van Duijn C, Spector T, Kiel D, Stefansson K, Ioannidis J, Uitterlinden A; Genetic Factors for Osteoporosis (GEFOS) Consortium. Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nature Genetics 2009 Nov;41(11):1199-206. Epub 2009 Oct 4.