Prijatelj Vid, Grgic Olja, Uitterlinden André G, Wolvius Eppo B, Rivadeneira Fernando, Medina-Gomez Carolina
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD, the Netherlands; Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD, the Netherlands; The Generation R Study, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, the Netherlands.
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD, the Netherlands; The Generation R Study, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015, GD, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD, the Netherlands.
Bone. 2024 May;182:117070. doi: 10.1016/j.bone.2024.117070. Epub 2024 Mar 7.
Bone Health Index (BHI) has been proposed as a useful instrument for assessing bone health in children. However, its relationship with fracture risk remains unknown. We aimed to investigate whether BHI is associated with bone mineral density (BMD) and prevalent fracture odds in children from the Generation R Study. We also implemented genome-wide association study (GWAS) and polygenic score (PGS) approaches to improve our understanding of BHI and its potential. In total, 4150 children (49.4 % boys; aged 9.8 years) with genotyped data and bone assessments were included in this study. BMD was measured across the total body (less head following ISCD guidelines) using a GE-Lunar iDXA densitometer; and BHI was determined from the hand DXA scans using BoneXpert®. Fractures were self-reported collected with home questionnaires. The association of BHI with BMD and fractures was evaluated using linear models corrected for age, sex, ethnicity, height, and weight. We observed a positive correlation between BHI and BMD (ρ = 0.32, p-value<0.0001). Further, every SD decrease in BHI was associated with an 11 % increased risk of prevalent fractures (OR:1.11, 95 % CI 1.00-1.24, p-value = 0.05). Our BHI GWAS identified variants (lead SNP rs1404264-A, p-value = 2.61 × 10) mapping to the ING3/CPED1/WNT16 locus. Children in the extreme tails of the BMD PGS presented a difference in BHI values of -0.10 standard deviations (95% CI -0.14 to -0.07; p-value<0.0001). On top of the demonstrated epidemiological association of BHI with both BMD and fracture risk, our results reveal a partially shared biological background between BHI and BMD. These findings highlight the potential value of using BHI to screen children at risk of fracture.
骨健康指数（BHI）已被提议作为评估儿童骨健康的一种有用工具。然而，其与骨折风险的关系仍不明确。我们旨在调查在“R世代”研究中的儿童里，BHI是否与骨密度（BMD）及既往骨折几率相关。我们还采用了全基因组关联研究（GWAS）和多基因评分（PGS）方法，以增进我们对BHI及其潜力的理解。本研究共纳入了4150名有基因分型数据和骨评估数据的儿童（49.4%为男孩；年龄9.8岁）。使用GE-Lunar iDXA骨密度仪按照国际临床骨密度学会（ISCD）指南测量全身（不包括头部）的骨密度；并使用BoneXpert®通过手部双能X线吸收测定扫描来确定BHI。骨折情况通过家庭问卷进行自我报告收集。使用校正了年龄、性别、种族、身高和体重因素的线性模型评估BHI与BMD及骨折之间的关联。我们观察到BHI与BMD之间存在正相关（ρ = 0.32，p值<0.0001）。此外 BHI每降低1个标准差，既往骨折风险增加11%（比值比：1.11，95%置信区间1.00 - 1.24，p值 = 0.05）。我们的BHI全基因组关联研究确定了映射到ING3/CPED1/WNT16基因座的变异（领先单核苷酸多态性rs1404264 - A，p值 = 2.61×10）。骨密度多基因评分处于极端尾部的儿童，其BHI值相差 -0.10个标准差（95%置信区间 -0.14至 -0.07；p值<0.0001）。除了已证明的BHI与BMD及骨折风险之间的流行病学关联外，我们的结果揭示了BHI与BMD之间部分共享的生物学背景。这些发现凸显了使用BHI筛查有骨折风险儿童的潜在价值。
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