MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; The Alan Turing Institute, London, UK.
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Bone. 2021 Jun;147:115937. doi: 10.1016/j.bone.2021.115937. Epub 2021 Mar 22.
Osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci.
115 males and 99 females (aged 72-81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011-2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011-2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age.
Previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05).
Baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).
骨质疏松症的特征是骨矿物质密度（BMD）降低和骨折易感性增加。通过高分辨率外周定量计算机断层扫描（HR-pQCT）测量的骨微结构与脆性骨折和 BMD 有关，并已成为大规模全基因组分析的主题。我们研究了骨折是否与骨微结构的基线值和纵向变化有关，以及骨微结构是否与已建立的 BMD 位点有关。
对赫特福德郡队列研究（HCS）中的 115 名男性和 99 名女性（基线时年龄为 72-81 岁）进行了分析。通过自我报告和椎体骨折评估，在 2011-2012 年确定了骨折史。参与者在 2011-2012 年和 2017 年接受了远端桡骨和胫骨的 HR-pQCT 扫描。使用经过性别调整的逻辑回归，在不调整和调整年龄、社会人口统计学、生活方式和临床特征的情况下，检查了基线值和胫骨 HR-pQCT 参数变化与既往骨折的关系；在调整性别和年龄后，检查了与四个已建立的 BMD 位点相关的基线值和参数变化与既往骨折的关系。
既往骨折与：较高的小梁面积（全调整优势比[95%置信区间]每 SD 较大基线值：2.18 [1.27,3.73]，p=0.005）；较低的总容积 BMD（0.53 [0.34,0.84]，p=0.007）、皮质面积（0.53 [0.30,0.95]，p=0.032）、皮质 BMD（0.56 [0.36,0.88]，p=0.011）和皮质厚度（0.45 [0.27,0.77]，p=0.004）；以及小梁 BMD 下降幅度更大（p=0.001）。在性别和全调整分析中，相关性是稳健的。BMD 位点与这些 HR-pQCT 参数之间的关系较弱：rs3801387（WNT16）与小梁 BMD 下降有关（p=0.011），但其他关联无统计学意义（p>0.05）。
HR-pQCT 参数的基线值和小梁 BMD 的更大下降与骨折有关。小梁 BMD 的变化与 WNT16 有关，WNT16 已在小鼠模型和人类全基因组关联研究（GWAS）中证明可影响骨骼健康。
