Simon Mathieu, Indermaur Michael, Schenk Denis, Hosseinitabatabaei Seyedmahdi, Willie Bettina M, Zysset Philippe
ARTORG Centre for Biomedical Engineering Research, University of Bern, Bern, Switzerland.
ARTORG Centre for Biomedical Engineering Research, University of Bern, Bern, Switzerland.
Bone. 2022 Feb;155:116282. doi: 10.1016/j.bone.2021.116282. Epub 2021 Dec 8.
Osteogenesis Imperfecta (OI) is an inherited form of bone fragility characterised by impaired synthesis of type I collagen, altered trabecular bone architecture and reduced bone mass. High resolution peripheral computed tomography (HR-pQCT) is a powerful method to investigate bone morphology at peripheral sites including the weight-bearing distal tibia. The resulting 3D reconstructions can be used as a basis of micro-finite element (FE) or homogenized finite element (hFE) models for bone strength estimation. The hFE scheme uses homogenized local bone volume fraction (BV/TV) and anisotropy information (fabric) to compute healthy bone strength within a reasonable computation time using fabric-elasticity relationships. However, it is unclear if these relationships quantified previously for healthy controls are valid for trabecular bone from OI patients. Thus, the aim of this study is to investigate fabric-elasticity relationships in OI trabecular bone compared to healthy controls. In the present study, the morphology of distal tibiae from 50 adults with OI were compared to 120 healthy controls using second generation HR-pQCT. Six cubic regions of interest (ROIs) were selected per individual in a common anatomical region. A first matching between OI and healthy control group was performed by selecting similar individuals to obtain identical mean and median age and sex distribution. It allowed us to perform a first morphometric analysis and compare the outcome with literature. Then, stiffness tensors of the ROIs were computed using μFE and multiple linear regressions were performed with the Zysset-Curnier orthotropic fabric-elasticity model. An initial fit was performed on both the OI group and the healthy control group using all extracted ROIs. Then, data was filtered according to a fixed threshold for a defined coefficient of variation (CV) assessing ROI heterogeneity and additional linear regressions were performed on these filtered data sets. These full and filtered data were in turn compared with previous results from μCT reconstructions obtained in other anatomical locations. Finally, the ROIs of both groups were matched according to their BV/TV and degree of anisotropy (DA). Linear regressions were performed using these matched data to detect statistical differences between the two groups. Compared to healthy controls, we found the OI samples to have significantly lower BV/TV and trabecular number (Tb.N.), significantly higher CV, trabecular separation (Tb.Sp.) and trabecular separation standard deviation (Tb.Sp.SD), but no differences in trabecular thickness (Tb.Th.). These results are in agreement with previous studies. The stiffnesses of highly heterogeneous ROIs were randomly lower with respect to the fabric-elasticity relationships, which reflects the limit of validity of the computational homogenisation methodology. This limitation does not challenge the fabric-elasticity relationship, which extrapolation to heterogeneous ROIs is probably reasonable but can simply not be evaluated with the employed homogenisation methodology. Moreover, due to their low BV/TV, the potential (unknown) errors on these heterogeneous ROIs would have negligible influence on whole bone stiffness in comparison to homogeneous ROIs which are orders of magnitude stiffer. The filtering of highly heterogeneous ROIs removed these low stiffness ROIs and led to similar correlation coefficients for both OI and healthy groups. Finally, the BV/TV and DA matched data revealed no significant differences in fabric-elasticity parameters between OI and healthy individuals. Moreover, the filtering step did not exclude a particular OI type. Compared to previous studies, the stiffness constants from the 61 μm resolution HR-pQCT ROIs were lower than for the 36 μm resolution μCT ROIs. In conclusion, OI trabecular bone of the distal tibia was shown to be significantly more heterogeneous and have a lower BV/TV than healthy controls. Despite the reduced linear regression parameters found for HR-pQCT images, the fabric-elasticity relationships between OI and healthy individuals are similar when the trabecular bone ROIs are sufficiently homogeneous to perform the computational stiffness analysis. Accordingly, the elastic properties used for FEA of healthy bones are also valid for OI bones.
成骨不全症(OI)是一种遗传性骨脆性疾病,其特征为I型胶原蛋白合成受损、小梁骨结构改变和骨量减少。高分辨率外周计算机断层扫描(HR-pQCT)是一种强大的方法,可用于研究包括负重的胫骨远端在内的外周部位的骨形态。由此产生的三维重建可作为微有限元(FE)或均匀化有限元(hFE)模型的基础,用于估计骨强度。hFE方案使用均匀化的局部骨体积分数(BV/TV)和各向异性信息(结构),通过结构-弹性关系在合理的计算时间内计算健康骨强度。然而,目前尚不清楚先前为健康对照量化的这些关系是否适用于OI患者的小梁骨。因此,本研究的目的是研究与健康对照相比,OI小梁骨中的结构-弹性关系。在本研究中,使用第二代HR-pQCT将50名成年OI患者的胫骨远端形态与120名健康对照进行比较。在每个个体的一个共同解剖区域中选择六个立方感兴趣区域(ROI)。通过选择相似个体以获得相同的平均和中位数年龄及性别分布,在OI组和健康对照组之间进行首次匹配。这使我们能够进行首次形态计量分析,并将结果与文献进行比较。然后,使用μFE计算ROI的刚度张量,并使用Zysset-Curnier正交各向异性结构-弹性模型进行多元线性回归。使用所有提取的ROI对OI组和健康对照组进行初始拟合。然后,根据固定阈值对定义的变异系数(CV)进行数据过滤,以评估ROI的异质性,并对这些过滤后的数据集进行额外的线性回归。这些完整和过滤后的数据依次与先前在其他解剖位置获得的μCT重建结果进行比较。最后,根据两组ROI的BV/TV和各向异性程度(DA)进行匹配。使用这些匹配数据进行线性回归,以检测两组之间的统计学差异。与健康对照相比,我们发现OI样本的BV/TV和小梁数量(Tb.N.)显著降低,CV、小梁间距(Tb.Sp.)和小梁间距标准差(Tb.Sp.SD)显著升高,但小梁厚度(Tb.Th.)无差异。这些结果与先前的研究一致。高度异质ROI的刚度相对于结构-弹性关系随机降低,这反映了计算均匀化方法有效性的局限性。这种局限性并不挑战结构-弹性关系,将其外推到异质ROI可能是合理的,但使用所采用的均匀化方法根本无法评估。此外,由于其低BV/TV,与刚度高几个数量级的均匀ROI相比,这些异质ROI上潜在的(未知)误差对整个骨刚度的影响可以忽略不计。对高度异质ROI的过滤去除了这些低刚度ROI,并导致OI组和健康组的相关系数相似。最后,BV/TV和DA匹配数据显示,OI个体和健康个体之间的结构-弹性参数无显著差异。此外,过滤步骤并未排除特定的OI类型。与先前的研究相比,61μm分辨率HR-pQCT ROI的刚度常数低于36μm分辨率μCT ROI的刚度常数。总之,与健康对照相比,胫骨远端的OI小梁骨显示出明显更高的异质性和更低的BV/TV。尽管HR-pQCT图像的线性回归参数降低,但当小梁骨ROI足够均匀以进行计算刚度分析时,OI个体和健康个体之间的结构-弹性关系相似。因此,用于健康骨有限元分析的弹性特性也适用于OI骨。