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27-03-2012 | Bone health | Article

Low-normal estrogen levels ‘may reduce hip fracture risk’


Free abstract

MedWire News: The incidence of hip fracture in postmenopausal women is inversely associated with estradiol levels and estrogen receptor (ER) activity, a case-control study has found.

The role of estrogens at physiologic concentrations in determining fracture risk is controversial, explain Woon-Puay Koh (National University of Singapore) and co-workers writing in Bone. In particular, there is a lack of data in Asian populations, which are known to have different estrogenic profiles to Caucasian populations.

To investigate, Koh et al obtained information on participants in the Singapore Chinese Health Study, a population-based prospective cohort involving more than 35,000 women.

A total of 140 women suffered a hip fracture during the study, with fractures occurring 4.4 years, on average, after enrollment. These 140 women were matched for age with 278 women who remained fracture-free throughout follow up.

The women's mean age was 69.3 years and case and control women were well-matched at baseline for body mass index, ethnicity, and level of education. However, women who suffered a fracture were more likely than controls to be current smokers, to be physically inactive, and to have a history of stroke and diabetes mellitus.

A comparison of blood samples revealed that women with incident hip fracture had significantly lower levels of free estradiol than those without fracture, at 1.10 vs 1.27 pM.

Levels of estradiol were also lower in women with hip fracture than in those without, but the difference did not reach statistical significance. Importantly, however, hip fracture risk significantly inversely correlated with levels of both free estradiol and ERα-mediated estrogenic activity.

After adjusting for confounders, and using women in the lowest quintile as the reference, those in the top quintile of free estradiol and ERα-mediated estrogenic activity had odds ratios for hip fracture of 0.43 and 0.53, respectively.

The interaction between the two biomarkers was not statistically significant, however, indicating that they might act via independent mechanistic pathways in the prevention of osteoporosis, say the researchers.

Koh et al conclude: "High levels of free estradiol and ERα-mediated estrogenic activity in sera were associated with decreased risk of osteoporotic hip fracture.

"The evaluation of therapeutic strategies including ultra-low-dose estrogen therapy such as a quarter of the regular dose or selective ER agonists may be warranted to reduce hip fracture for women with low serum estrogenicity."

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Joanna Lyford

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