Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
J Bone Miner Res. 2017 Aug;32(8):1607-1614. doi: 10.1002/jbmr.3123. Epub 2017 Mar 30.
The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16-1.48), and hip fractures (HR = 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 μg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 μg/mL are at highest risk. © The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
肾上腺源性激素脱氢表雄酮（DHEA）及其硫酸盐（DHEAS）是循环中最丰富的激素，其水平随年龄的增长而显著下降。DHEAS 被认为是一种无活性的前体，可通过外周靶组织的局部代谢转化为雄激素和雌激素。血清 DHEAS 对骨折风险的预测价值尚不清楚。因此，本研究旨在评估在瑞典一项大型老年男性人群的基础研究中，基线 DHEAS 水平与新发骨折之间的相关性。采用瑞典骨质疏松性骨折男性研究（Osteoporotic Fractures in Men study in Sweden，OFS）中的人群队列，用质谱分析法对血清 DHEAS 水平进行了分析（n=2568，年龄 69 岁至 81 岁）。在中位随访 10.6 年期间，确定了 X 射线验证的新发骨折（所有，n=594；非椎体主要骨质疏松性，n=255；髋部，n=175；临床椎体，n=206）。Cox 回归模型校正年龄、体重指数（BMI）和既往骨折后，DHEAS 水平与任何骨折（每 SD 下降的危险比 [HR] =1.14，95%置信区间 [CI] 1.05-1.24）、非椎体主要骨质疏松性骨折（HR=1.31，95%CI 1.16-1.48）和髋部骨折（HR=1.18，95%CI 1.02-1.37）风险呈负相关，但与临床椎体骨折（HR=1.09，95%CI 0.95-1.26）无关。进一步调整骨折的传统危险因素、骨密度（BMD）和/或体能变量以及血清性激素水平后，DHEAS 与骨折风险之间的相关性也仅略有减弱。同样，在用 BMD 校正 FRAX 估计值后，点估计值也仅略有降低。血清 DHEAS 与所有骨折或主要骨质疏松性骨折之间的负相关是非线性的，对于血清 DHEAS 水平低于中位数（0.60μg/mL）的参与者，骨折风险显著增加（所有骨折 22%，主要骨质疏松性骨折 33%）。总之，血清 DHEAS 水平较低是老年男性发生非椎体骨折的危险因素，其中血清 DHEAS 水平低于 0.60μg/mL 的参与者风险最高。
