Chapurlat R D, Garnero P, Bréart G, Meunier P J, Delmas P D
INSERM Unit 403, Hôpital Edouard Herriot, Lyon, France.
J Bone Miner Res. 2000 Sep;15(9):1835-41. doi: 10.1359/jbmr.2000.15.9.1835.
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.
有人提出，血清17β-雌二醇（E2）和性激素结合球蛋白（SHBG）水平低可能预示绝经后女性髋部骨折风险。我们在一项针对7598名75岁及以上健康老年非卧床女性的大型前瞻性队列研究（EPIDOS研究）中，研究了血清E2和SHBG浓度以及尿脱氧吡啶啉（D-Pyr）和I型胶原降解产物（CTX）的预测价值。我们进行了一项巢式病例对照研究，将212例新发髋部骨折患者与636例对照进行匹配。平均随访时间为3.3年（最长4.9年）。血清E2低于检测下限（3 pg/ml）的女性，即占总人群2%的女性，骨折风险并未升高，相对风险（RH）为1.59（95%置信区间=0.45-5.55）。血清E2低于5、6、7或8 pg/ml、处于最低四分位数或低于中位数的女性，髋部骨折风险并未增加。相反，血清E2处于最高四分位数（即≥10 pg/ml）的女性受到保护，RH为0.66（0.44-0.98），但在调整体重后该差异不再显著（RH=0.71[0.47-1.06]）。不同临界值的高血清SHBG值往往与髋部骨折风险增加相关。最高四分位数的女性与最低四分位数的女性相比，RH为2.5（1.37-4.61），在调整体重后显著降低（1.61[0.99-2.62]）。作为游离E2指标的E2/SHBG比值最高四分位数与较低的髋部骨折风险相关（RH=0.6[0.4-0.91]），但在调整体重后该差异不再显著。相反，尿D-Pyr和CTX高于绝经前上限时可预测髋部骨折，即使在调整体重、血清E2和SHBG后，其RH分别为2.07（1.49-2.9）和1.67（1.19-2.32）。我们得出结论，在75岁以上健康的法国老年女性中，血清E2和E2/SHBG最高四分位数与较低的髋部骨折风险相关，且这种关联可通过较高的体重来解释。此外，血清E2和SHBG水平并不能解释与高水平骨吸收标志物相关的髋部骨折风险增加。
