Ascenzi Maria-Grazia, Chin Jesse, Lappe Joan, Recker Robert
Department of Orthopaedic Surgery, University of California, Los Angeles, USA.
Department of Medicine, Creighton University, Omaha, USA.
Bone. 2016 Mar;84:104-112. doi: 10.1016/j.bone.2015.10.010. Epub 2015 Oct 26.
Areal bone mineral density (BMD) by DXA, although an important index, does not accurately assess risk of fragility fracture. Another bone structural parameter, the orientation of type I collagen, is known to add to risk determination, independently of BMD. Accordingly, we investigated the Haversian systems of transiliac crest biopsies from non-osteoporotic women with low-trauma fractures, matched to healthy women without fracture by age and BMD. We employed circularly polarized light (CPL) microscopy because 1) each of the extinct and bright birefringent signals of CPL corresponds to a specific collagen arrangement; and 2) CPL can employ magnification suitable to provide data, of manageable size, from the whole cortical component of a section of biopsy. Under CPL, the coaxial layers of osteons, called lamellae, appear either birefringent extinct or bright. On a section transverse to the Haversian system, the extinct lamella comprises mainly collagen forming small angles, and the bright lamella comprises mainly collagen forming large angles, relative to the general orientation of the Haversian system. We performed semi-automatic morphometry for birefringent and structural parameters for which we computed intra- and inter-observer errors. The statistical analysis used a linear mixed model to compare fracturing and non-fracturing groups while addressing pairing of fracturing and non-fracturing subjects, and linear regression to assess differences between matched subjects. We found significant reduction in 1) lamellar width and area for extinct lamella and bright lamella; 2) percentage of extinct birefringence in osteons, and 3) single osteon area; in the fracturing group; and in lamellar width in the fracturing subject of all pairs. Our results evidence the need to investigate, in a larger sample of subjects, the distribution of collagen orientation as a parameter diagnostic of increased fracture risk.
通过双能X线吸收法(DXA)测量的面积骨密度(BMD)虽是一项重要指标,但并不能准确评估脆性骨折风险。另一个骨结构参数,即I型胶原蛋白的取向,已知可独立于BMD增加风险判定。因此,我们研究了低创伤骨折的非骨质疏松女性的髂嵴活检标本中的哈弗斯系统,并按照年龄和BMD与无骨折的健康女性进行匹配。我们采用圆偏振光(CPL)显微镜,原因如下:1)CPL的消光和明亮双折射信号各自对应特定的胶原蛋白排列;2)CPL可采用适合提供活检切片整个皮质成分数据的放大倍数,且数据量易于管理。在CPL下,骨单位的同轴层(即板层)呈现消光或明亮的双折射。在与哈弗斯系统横向的切片上,消光板层主要包含与哈弗斯系统总体取向形成小角度的胶原蛋白,而明亮板层主要包含与哈弗斯系统总体取向形成大角度的胶原蛋白。我们对双折射和结构参数进行了半自动形态测量,并计算了观察者内和观察者间误差。统计分析采用线性混合模型比较骨折组和非骨折组,同时考虑骨折组和非骨折组受试者的配对情况,并采用线性回归评估匹配受试者之间的差异。我们发现骨折组中:1)消光板层和明亮板层的板层宽度和面积显著减小;2)骨单位中消光双折射的百分比,以及3)单个骨单位面积减小;并且所有配对中骨折受试者的板层宽度也减小。我们的结果表明,有必要在更大样本的受试者中研究胶原蛋白取向分布,将其作为骨折风险增加的诊断参数。