High Estradiol Levels Reduce Risk of Nonspine Fractures

From the American Society for Bone and Mineral Research Potential Alternative to BMD Measures for Guiding Therapy

PHILADELPHIA—High endogenous estradiol levels appear to be associated with a decreased risk of nonspine fractures, including wrist and hip fractures, according to results from a prospective study presented at the annual meeting of the American Society for Bone and Mineral Research. This relationship may be mediated, in part, by bone mineral density (BMD). If these new findings are confirmed, serum estradiol levels may serve as a useful independent marker for fracture risk.

Previous studies have shown a correlation between higher endogenous estradiol levels and a reduced risk for hip fractures and vertebral fractures, but the effect on the incidence of nonspine fractures was unknown.

This study included 411 women (mean age, 71.5 years) from the Study of Osteoporotic Fractures who were not current users of hormone replacement therapy whose total endogenous estradiol serum sample had been stored at —190°C since baseline in 1986-1988. Endogenous estradiol levels were measured with a direct assay from 1 of 2 commercial laboratories. Bioavailable estradiol was calculated from total estradiol and previously measured sex hormone–binding globulin.

During a mean follow-up of 11.1 years, 159 women (39%) had ≥1 nonspine fractures, including 41 hip and 32 wrist fractures.

Women who had and those who did not have a nonspine fracture during follow-up were similar in age (71.8 vs 71.6 years, respectively) and had a similar body mass index (26.6 vs 27.1 kg/m²), but those with nonspine fractures had lower hip BMD (0.73 vs 0.79 g/cm²).

Women in the highest quartile of total endogenous estradiol had a 34% lower risk of nonspine fractures compared with women in the lower 3 quartiles of total endogenous estradiol. The relationship with bioavailable endogenous estradiol was similar.

“Bone mineral density is a good predictor of fractures, but it is not a perfect predictor. Our hope is that we can combine other factors, such as clinical risk factors and perhaps estradiol measurements, to improve ability to predict who is going to have a fracture,” lead investigator Douglas Bauer, MD, professor of medicine, epidemiology, and biostatistics at the University of California, San Francisco, told IMWR.

“If you identify a woman who is at moderate risk based on bone mineral density and other risk factors, and yet she has a very high level of endogenous estradiol, you might forego treatment, because the likelihood of her having a fracture is lower than a woman who has a lower level of estradiol,” said Dr Bauer.

Measuring estradiol levels may also offer insights into the risks associated with breast cancer and possibly with cardiovascular disease. Dr Bauer noted that the currently used assays are vastly improved over those used in the past.