Results from a large study indicate that variants of the gene LRP5 are associated with a significant increase in the risk of fractures, by up to 20 percent, and lower levels of bone mineral density in the spine and hip, according to a study in the March 19 issue of JAMA, a theme issue on Genetics and Genomics.
Joyce B. J. van Meurs, Ph.D., of Erasmus MC, Rotterdam, the Netherlands, presented the findings of the study at a JAMA media briefing at the National Press Club in Washington, D.C.
Osteoporosis is characterized by low bone mineral density (BMD), deterioration of bone and increased risk for fractures. Studies have shown that genetic factors determine up to 80 percent of the variance in BMD, which is a major predictor of osteoporotic fractures, according to background information in the article. While the genes that contribute to differences in risk for osteoporosis and osteoporotic fractures are for the most part unknown, it is thought that the risk of developing osteoporosis is dependent on several common gene variants. Variations of the gene LRP5 have been linked to bone mass accrual and susceptibility to osteoporosis, and some reports have suggested that some of these variants contribute to change in BMD in the general population, but results have been inconclusive, partly because of small sample size.
Dr. van Meurs and colleagues examined the association between variants to the genes LRP5 and LRP6 to BMD and risk of fracture using large-scale evidence, with the combined analysis of individual-level data of the full Genetic Markers for Osteoporosis (GENOMOS) consortium, including data from 37,534 individuals from 18 participating teams in Europe and North America. Bone mineral density was assessed by dual-energy x-ray absorptiometry (an imaging technique). Fractures were identified via questionnaire, medical records, or radiographic documentation; new fracture data were available for some groups, determined via routine surveillance methods, including radiographic examination for vertebral fractures.