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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >A Polygenic Risk Score as a Risk Factor for Medication-Associated Fractures
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A Polygenic Risk Score as a Risk Factor for Medication-Associated Fractures

机译：多基因风险评分作为药物相关骨折的危险因素

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Some commonly prescribed drugs are associated with increased risk of osteoporotic fractures. However, fracture risk stratification using skeletal measures is not often performed to identify those at risk before these medications are prescribed. We tested whether a genomically predicted skeletal measure, speed of sound (gSOS) from heel ultrasound, which was developed in 341,449 individuals from UK Biobank and tested in a separate subset consisting of 80,027 individuals, is an independent risk factor for fracture in users of fracture-related drugs (FRDs). To do this, we first assessed 80,014 UK Biobank participants (including 12,678 FRD users) for incident major osteoporotic fracture (MOF,n= 1189) and incident hip fracture (n= 209). Effects of gSOS on incident fracture were adjusted for baseline clinical fracture risk factors. We found that each standard deviation decrease in gSOS increased the adjusted odds of MOF by 42% (95% confidence interval [CI] 1.34-1.51,p < 2 x 10(-16)) and of hip fracture by 31% (95% CI 1.15-1.50,p= 9 x 10(-5)). gSOS below versus above the mean increased the adjusted odds of MOF by 79% (95% CI 1.58-2.01,p < 2 x 10(-16)) and of hip fracture by 42% (95% CI 1.08-1.88,p= 1.3 x 10(-2)). Among FRD users, each standard deviation decrease in gSOS increased the adjusted odds of MOF by 29% (n(MOF)= 256, 95% CI 1.14-1.46,p= 7 x 10(-5)) and of hip fracture by 30% (n(hip fracture)= 68, 95% CI 1.02-1.65,p= 0.0335). FRD users with gSOS below versus above the mean had a 54% increased adjusted odds of MOF (95% 1.19-1.99,p= 8.95 x 10(-4)) and a twofold increased adjusted odds of hip fracture (95% 1.19-3.31,p= 8.5 x 10(-3)). We therefore showed that genomically predicted heel SOS is independently associated with incident fracture among FRD users. (c) 2020 American Society for Bone and Mineral Research.
机译：一些常用的处方药与骨质疏松性骨折的风险增加有关。然而，在处方这些药物之前，通常不使用骨骼测量来进行骨折风险分层，以识别风险人群。我们测试了在英国生物银行（Biobank）的341449名受试者中开发的、由80027名受试者组成的单独子集中测试的、通过足跟超声进行基因组预测的骨骼测量、声速（gSOS）是否是骨折相关药物（FRD）使用者骨折的独立风险因素。为此，我们首先评估了80014名英国Biobank参与者（包括12678名FRD使用者）的严重骨质疏松性骨折（MOF，n=1189）和髋部骨折（n=209）。根据基线临床骨折风险因素调整GSO对偶发骨折的影响。我们发现，gSOS的每一个标准差降低，MOF的校正几率增加42%（95%置信区间[CI]1.34-1.51，p<2 x 10（-16）），髋部骨折的校正几率增加31%（95%置信区间1.15-1.50，p=9 x 10（-5））。gSOS低于平均值与高于平均值相比，MOF的校正几率增加79%（95%可信区间1.58-2.01，p<2 x 10（-16）），髋部骨折的校正几率增加42%（95%可信区间1.08-1.88，p=1.3 x 10（-2））。在FRD使用者中，GSO的每一个标准差降低都会使MOF的校正几率增加29%（n（MOF）=256，95%可信区间1.14-1.46，p=7 x 10（-5）），髋部骨折的校正几率增加30%（n（髋部骨折）=68，95%可信区间1.02-1.65，p=0.0335）。GSO低于平均值与高于平均值的FRD患者的MOF校正几率增加了54%（95%1.19-1.99，p=8.95 x 10（-4）），髋部骨折校正几率增加了两倍（95%1.19-3.31，p=8.5 x 10（-3））。因此，我们表明，基因组预测的足跟SOS与FRD使用者中的意外骨折独立相关。（c） 2020年美国骨与矿物研究学会。

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