title: Serum estradiol and sex hormone-binding globulin and the risk of hip fracture in elderly women: the EPIDOS study.
abstract: It has been suggested that low serum 17beta-estradiol (E2) and sex hormone-binding globulin (SHBG) may predict hip fracture in postmenopausal women. We have investigated the predictive value of serum E2 and SHBG concentrations and urinary deoxypyridinoline (D-Pyr) and type I collagen breakdown products (CTX) in a large prospective cohort of 7,598 healthy elderly ambulatory women (EPIDOS study), aged 75 years or more. We performed a nested case control study, by matching 212 patients with incident hip fracture with 636 controls. Mean follow-up was 3.3 years (maximum, 4.9 years). Women having serum E2 below the limit of detection (3 pg/ml), that is, 2% of the population, were not at higher risk, with a relative hazard (RH) of 1.59 (95% CI = 0.45-5.55). Women having serum E2 below 5, 6, 7, or 8 pg/ml, in the lowest quartile, or below the median had no increased risk of hip fracture. In contrast, women having serum E2 in the highest quartile (i.e., > or = 10 pg/ml) were protected, with an RH of 0.66 (0.44-0.98) that did not remain significant after adjustment for weight (RH = 0.71 [0.47-1.06]). High serum SHBG values with different cut-offs tended to be associated with an increased risk of hip fracture. Women in the highest quartile had an RH of 2.5 (1.37-4.61), compared with those in the lowest quartile, that decreased markedly after adjustment for body weight (1.61 [0.99 -2.62]). The highest quartile of the ratio E2/SHBG, which is an index of free E2, was associated with a lower hip fracture risk (RH = 0.6 [0.4-0.91]) that was no longer significant after adjustment for weight. In contrast, urinary D-Pyr and CTX, when elevated above the upper limit of premenopausal values, were predictive of hip fracture, with an RH of 2.07 (1.49-2.9) and 1.67 (1.19-2.32), respectively, even after adjustment for body weight, serum E2, and SHBG. We conclude that in healthy elderly French women over 75 years of age, serum E2 and E2/SHBG in the highest quartile are associated with a lower risk of hip fracture and that this association is explained by a higher body weight. In addition, serum levels of E2 and SHBG do not account for the increased risk of hip fracture associated with high levels of bone resorption markers.
authors.affiliation: INSERM Unit 403, Hôpital Edouard Herriot, Lyon, France.
authors.forename: R D
authors.initials: RD
authors.lastname: Chapurlat
authors.forename: P
authors.initials: P
authors.lastname: Garnero
authors.forename: G
authors.initials: G
authors.lastname: Bréart
authors.forename: P J
authors.initials: PJ
authors.lastname: Meunier
authors.forename: P D
authors.initials: PD
authors.lastname: Delmas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D001835:Body Weight; D015519:Bone Density; D001862:Bone Resorption / Q000097:blood / Q000209:etiology / Q000378:metabolism; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood*; D005260:Female; D005270:Femur Head / Q000503:physiopathology; D005602:France; D006620:Hip Fractures / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011237:Predictive Value of Tests; D017697:Premenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol