A new study has isolated five gene regions that are linked to bone density, which could lead to future treatments for diseases such as osteoporosis.
Researchers in Iceland analyzed data from the genetic codes of 8,000 people in Iceland, Denmark and Australia. They found five genomic regions that were closely tied to bone density.
"We showed that not only do these genes have variants associated with bone mineral density but we also showed that they associate with the tendency to suffer low-impact fractures," lead study author Dr. Kari Stefansson told CTV.ca.
Stefansson said that these gene sets will not indicate a person's risk for developing osteoporosis.
"When you make a discovery like this, it first and foremost helps us to understand the disease," Stefansson said.
"It shows us what biochemical pathways are involved, and by doing so if offers us an opportunity to seek new drug targets for the prevention and treatment of disease."
In fact, Stefansson said that one of the genes has been used to develop a new drug treatment that is currently undergoing clinical trials.
The researchers had set out to identify genes related to bone density and fracture because, as the authors said in their study, "Bone density is the single best predictor of osteoporotic fractures and is a valuable tool in evaluation of the risk of fractures."
The findings were published Tuesday in The New England Journal of Medicine.
According to Osteoporosis Canada, osteoporosis is a disease characterized by low bone mass and the degradation of bone tissue. This leaves patients susceptible to hip, spine, arm and other fractures.
About 1.4 million Canadians have osteoporosis. An estimated one in four women, and about one in eight men, over the age of 50 suffer from the disease.
Abstract:
Multiple Genetic Loci for Bone Mineral Density and Fractures
Unnur Styrkarsdottir, Ph.D., Bjarni V. Halldorsson, Ph.D., Solveig Gretarsdottir, Ph.D., Daniel F. Gudbjartsson, Ph.D., G. Bragi Walters, B.Sc., Thorvaldur Ingvarsson, M.D., Ph.D., Thorbjorg Jonsdottir, B.Sc., Jona Saemundsdottir, B.Sc., Jacqueline R. Center, M.B., B.S., Ph.D., Tuan V. Nguyen, Ph.D., Yu Bagger, M.D., Jeffrey R. Gulcher, M.D., Ph.D., John A. Eisman, M.B., B.S., Ph.D., Claus Christiansen, M.D., Gunnar Sigurdsson, M.D., Ph.D., Augustine Kong, Ph.D., Unnur Thorsteinsdottir, Ph.D., and Kari Stefansson, M.D., Ph.D.
Background: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture.
Methods: We performed a quantitative trait analysis of data from 5861 Icelandic subjects (the discovery set), testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. We then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively).
Results: Sequence variants in five genomic regions were significantly associated with bone mineral density in the discovery set and were confirmed in the replication sets (combined P values, 1.2x10-7 to 2.0x10-21). Three regions are close to or within genes previously shown to be important to the biologic characteristics of bone: the receptor activator of nuclear factor- B ligand gene (RANKL) (chromosomal location, 13q14), the osteoprotegerin gene (OPG) (8q24), and the estrogen receptor 1 gene (ESR1) (6q25). The two other regions are close to the zinc finger and BTB domain containing 40 gene (ZBTB40) (1p36) and the major histocompatibility complex region (6p21). The 1p36, 8q24, and 6p21 loci were also associated with osteoporotic fractures, as were loci at 18q21, close to the receptor activator of the nuclear factor- B gene (RANK), and loci at 2p16 and 11p11.
Conclusions: We have discovered common sequence variants that are consistently associated with bone mineral density and with low-trauma fractures in three populations of European descent. Although these variants alone are not clinically useful in the prediction of risk to the individual person, they provide insight into the biochemical pathways underlying osteoporosis.
