In a ground-breaking genome study, UK researchers leading a team from the Netherlands, Canada and Australia have identified genetic variants which decrease bone mineral density and predispose people to osteoporosis and osteoporotic fracture. Screening for these two genes variants, carried by over 20% of the population, can in the future be used alongside known environmental factors to help determine those at risk of osteoporosis.

The team studied the whole genome of 8557 people from several European countries. The results revealed two single nucleotide polymorphisms (SNPs) associated with decreased bone mineral density and increased osteoporosis.

The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density and an increased risk of both osteoporotic fractures  and osteoporosis. Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density and increased risk of osteoporosis. The presence of both risk variants, as was the case in more than one in five subjects, increased the risk of osteoporotic fractures by more than 30%, suggesting a strong argument for screening.

In identifying environmental risk factors, the WHO lists low bone mineral density, low body-mass index, previous fragility fractures, glucocorticoid exposure, parental history of  osteoporotic fracture, smoking, excessive alcohol intake, and rheumatoid arthritis as having a clear role in osteoporosis. Now, in this new study
the risk attributed to the presence of both genetic variants was similar to or greater than all of the environmental risk factors except prior fragility fractures and bone mineral density.

“These alleles can be measured with near-perfect precision years before the age at which fractures tend to occur — which could provide ample lead-time for preventive treatments to be implemented,” the researchers state in the Lancet. “Eventually, a panel of genetic markers could be used in addition to environmental risk factors to identify individuals who are most at risk for osteoporotic fractures.”

“Furthermore, the identification of genetic variants which decrease both bone mineral density and expression of osteoprotegerin suggests that people with these variants might respond best to medications which increase osteoprotegerin concentrations. The existence of such medications allows the opportunity for personalised medicine on the basis of these genetic markers,” researchers said.

Reference
Richards JB et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 2008;3;371(9623):1505-12.

To view the article, please see
http://www.ncbi.nlm.nih.gov/pubmed/18455228