High SHBG and Low Bioavailable Testosterone are Strongly Causally Associated with Increased Forearm Fracture Risk in Women: An MR Study Leveraging Novel Female-Specific Data.

IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Calcified Tissue International Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI:10.1007/s00223-024-01301-5
Johan Quester, Maria Nethander, Eivind Coward, Ene Reimann, Reedik Mägi, Ulrika Pettersson-Kymmer, Kristian Hveem, Claes Ohlsson
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引用次数: 0

Abstract

The effects of androgens on women's bone health are not fully understood. Mendelian randomization (MR) studies using sex-combined data suggest that sex hormone-binding globulin (SHBG) and bioavailable testosterone (BioT) causally affect bone traits. Given significant sex differences in hormone regulation and effects, female-specific MR studies are necessary. In the current study, we explored the causal relationships of SHBG, BioT, and total testosterone (TT) with forearm fracture (FAFx) risk in women using two-sample MR analyses. We utilized a unique female-specific FAFx outcome dataset from three European biobanks (UFO, HUNT, Estonian Biobank) comprising 111,351 women and 8823 FAFx cases, along with female-specific genetic instruments of SHBG, BioT, and TT identified in the UK Biobank. We also assessed bone mineral density (BMD) at the forearm (FA), femoral neck (FN), and lumbar spine (LS) using female-specific GWAS data from the GEFOS consortium. High SHBG (odds ratio per standard deviation increase (OR/SD): 1.53, 95% confidence intervals (CIs): 1.34-1.75), low BioT (OR/SD: 0.77, 0.71-0.84) and low TT (OR/SD 0.90, 0.83-0.98) were causally associated with increased FAFx risk. BioT was positively, and SHBG inversely, causally associated with especially FA-BMD, but also LS-BMD and FN-BMD, while TT was only significantly positively associated with FA-BMD and LS-BMD. We propose that endogenous androgens and SHBG are important for women's bone health at distal trabecular-rich bone sites such as the distal forearm and may serve as predictors for FAFx risk.

高 SHBG 和低生物可用睾酮与女性前臂骨折风险增加密切相关:利用新的女性特异性数据进行的磁共振研究。
雄激素对女性骨骼健康的影响尚不完全清楚。使用性别组合数据进行的孟德尔随机化(MR)研究表明,性激素结合球蛋白(SHBG)和生物可用睾酮(BioT)会对骨骼特征产生因果影响。鉴于激素调节和影响方面存在明显的性别差异,有必要开展针对女性的 MR 研究。在本研究中,我们利用双样本磁共振分析探讨了 SHBG、BioT 和总睾酮(TT)与女性前臂骨折(FAFx)风险的因果关系。我们利用了来自三个欧洲生物库(UFO、HUNT 和爱沙尼亚生物库)的独特女性特异性 FAFx 结果数据集,其中包括 111,351 名女性和 8823 个 FAFx 病例,以及英国生物库中确定的 SHBG、BioT 和 TT 的女性特异性遗传工具。我们还利用来自 GEFOS 联盟的女性特异性 GWAS 数据评估了前臂(FA)、股骨颈(FN)和腰椎(LS)的骨质密度(BMD)。高 SHBG(每标准差增加的几率比(OR/SD):1.53,95% 置信区间(CIs):1.34-1.75)、低 BioT(OR/SD:0.77,0.71-0.84)和低 TT(OR/SD 0.90,0.83-0.98)与 FAFx 风险增加存在因果关系。BioT与FA-BMD、LS-BMD和FN-BMD呈正相关,与SHBG呈反相关,而TT仅与FA-BMD和LS-BMD呈显著正相关。我们认为,内源性雄激素和 SHBG 对女性前臂远端等骨小梁丰富部位的骨骼健康非常重要,可作为 FAFx 风险的预测因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Calcified Tissue International
Calcified Tissue International 医学-内分泌学与代谢
CiteScore
8.00
自引率
2.40%
发文量
112
审稿时长
4-8 weeks
期刊介绍: Calcified Tissue International and Musculoskeletal Research publishes original research and reviews concerning the structure and function of bone, and other musculoskeletal tissues in living organisms and clinical studies of musculoskeletal disease. It includes studies of cell biology, molecular biology, intracellular signalling, and physiology, as well as research into the hormones, cytokines and other mediators that influence the musculoskeletal system. The journal also publishes clinical studies of relevance to bone disease, mineral metabolism, muscle function, and musculoskeletal interactions.
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