‘Osteogenomic profile’ offers personalized fracture risk assessment

Bone mineral density-associated genetic variants may predict lifetime fracture risk for men and women, study data show.

“There is a high variation in [residual lifetime risk for fracture] between individuals, and we hypothesize that the variation is partly due to genetic factors,” Thao Phuong Ho-Le, of the Centre for Health Technologies at the University of Technology Sydney in Australia, and colleagues wrote in an abstract. “Several genetic variants have been identified to be associated with BMD. This study sought to develop a genetic profiling of BMD-associated genetic variants for predicting the life risk of fracture for men and woman.”

In a population-based, prospective study, Ho-Le and colleagues analyzed data from 1,326 men and 2,189 women aged at least 60 years at study entry (between 1989 and 1992) and followed continuously for 20 years. Incidence of fragility fractures was determined by X-ray reports; femoral neck BMD was assessed by DXA. Researchers also created a polygenic risk score that included the weighted number of risk alleles for each single nucleotide polymorphism, with the weight being regression coefficients associated with BMD. Researchers estimated residual lifetime risk for fracture from age 60 years by survival analysis, considering the competing risk for death.

During 20 years of follow-up, 667 women (31%) and 239 men (18%) sustained at least one fracture. After adjusting for competing risk for death, residual lifetime risk for fracture from age 60 years was 36% for women (95% CI, 34-39) and 21% for men (95% CI, 18-24). Greater polygenic risk score was associated with higher lifetime risk for fracture. Among women and men with a polygenic risk score of at least 4.24 (median), lifetime fracture risk was 42% for women and 24% for men.

After adjustment for mortality, residual lifetime risk for fracture was 10% for women (95% CI, 8-12) and 5% for men (95% CI, 3-6), and a higher polygenic risk score was associated with a higher lifetime risk for hip fracture.

The association of polygenic risk score and residual lifetime risk for fracture was independent of femoral neck BMD, according to researchers.

“The finding raises the possibility of personalized fracture risk assessment by using an osteogenomic profile,” the researchers wrote. – by Regina Schaffer

Reference:

Ho-Le, et al. Abstract FR0089. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 8-11, 2017; Denver.

Disclosure: Ho-Le reports no relevant financial disclosures.