Genetics Are Key to Lowering Bone Fracture Risk

A study has found that postmenopausal women who are more genetically prone to fractures benefit most from hormone therapy (HT). The results therefore have implications that could advance personalized medicine for postmenopausal women.

“We found that women who are genetically at the highest fracture risk can enjoy the greatest protection from fracture when they use HT,” said Heather Ochs-Balcom, associate professor at University at Buffalo (Buffalo, NY, USA), who led the study team made up of researchers at UB and their collaborators at Ohio State University (USA) and University of California (USA). “This study provides a better understanding of who can benefit the most in terms of bone health from HT use,” she said, “It’s important information as women and their doctors make decisions.”

The study included nearly 10,000 participants from the Women’s Health Initiative (WHI), a national, long-term study begun in 1991 that consisted of a set of clinical trials and an observational study. Combined, they included over 161,000 generally healthy postmenopausal women aged 50-79. As one of 40 WHI centers nationwide, the University at Buffalo serves as the Northeast Regional Center.

The study, considered to be the first to investigate gene-HT interaction on fracture in postmenopausal white women, utilizes the largest set of known genes linked to fracture risk from a meta-analysis of genome-wide association studies. The researchers looked at a subset of 9,922 women from among the more than 27,000 that had participated in WHI hormone therapy clinical trials. They wondered whether women who are more genetically susceptible to fractures could benefit from hormone therapy.

“Our study represents a first look at how inherited predisposition to fracture is related to HT use,” said Prof Ochs-Balcom. “This is important because, as previous WHI studies have identified, there are risks and benefits with HT,” she noted, “This is where precision or personalized medicine comes in – the attempt to get the right drugs to the right person to ensure the most benefit and least harm.”

First author Youjin Wang, who conducted the research as a UB doctoral candidate, added, “further studies on gene-therapy interaction are warranted to evaluate the advantages of targeted interventions based on genetic profile.” The research team is currently analyzing other gene-environment interactions and recently published another study on the association of calcium plus vitamin D supplementation and genetic risk of fracture.

The study, by Wang Y et al, was published March 6, 2017, in the Journal of Clinical Endocrinology and Metabolism.