Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study.
Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study.
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DOI：
10.1002/jbmr.2759
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发表时间：
2016-05
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影响因子：
--
通讯作者：
Recker RR
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作者：
Boskey AL;Donnelly E;Boskey E;Spevak L;Ma Y;Zhang W;Lappe J;Recker RR
傅里叶变换红外成像（FTIRI）提供了薄组织标本的化学成分的空间分布的信息，空间分辨率约为7 μ m。本研究纳入了120例年龄和BMD匹配的患者，旨在研究髂嵴活检中测量的FTIRI变量与任何部位脆性骨折的相关性。早期对54名不同女性的研究发现，髋部BMD是皮质骨骨折风险的重要解释变量，但不是松质骨。在目前的研究中，通过配对控制年龄和BMD，没有发现这种关联，验证了配对方案。我们对不匹配的髂嵴活检的第一项研究发现，胶原成熟度（松质骨和皮质骨）和矿物晶体大小（仅皮质骨）的增加与其他协变量结合时是骨折的重要解释变量。胶原蛋白成熟度的比率与酶促胶原蛋白交联的量相关。为了评估其他FTIRI变量（酸性磷酸盐替代、碳酸盐/磷酸盐比值和所有相关FTIRI变量的像素分布（异质性））的影响，我们检查了一项匹配病例对照研究的活检标本，其中60名骨折女性分别与年龄和BMD匹配的女性对照配对。通过对120例女性患者的配对数据进行条件Logistic回归分析，发现骨折的显著解释变量是两个松质骨中碳酸盐/磷酸盐比值的降低（比值比=0.580，95%置信区间（CI）=[0.37，0.909]，p= 0.0176）和皮质骨（比值比= 0.519，95% CI=[0.325，0.829]，p= 0.0061），松质骨胶原成熟度的异质性增加（像素分布变宽）（比值比= 1.549，95% CI= [1.002，2.396]，p=0.0491）。在年龄和BMD匹配的样本中，胶原蛋白成熟度不再与骨折相关，这一观察结果表明，胶原蛋白成熟度的年龄依赖性变化可能是脆性骨折的一个比以前认为的更重要的促成因素。
Fourier transform infrared imaging (FTIRI) provides information on spatial distribution of the chemical composition of thin tissue specimens at ~7um spatial resolution. This study of 120 age-and BMD-matched patients was designed to investigate the association of FTIRI variables, measured in iliac crest biopsies, with fragility fractures at any site. An earlier study of 54 different women found hip BMD to be a significant explanatory variable of fracture risk for cortical bone, but not for cancellous bone. In the current study, where age and BMD were controlled through matching, no such association is seen, validating the pairing scheme. Our first study of un-matched iliac crest biopsies found increases in collagen maturity (cancellous and cortical bone) and mineral crystal size (cortical bone only) to be a significant explanatory variable of fracture when combined with other covariates. The ratio for collagen maturity has been correlated to the amount of enzymatic collagen cross-links. To assess the impact of other FTIRI variables (acid phosphate substitution, carbonate-to-phosphate ratio, and the pixel-distribution (heterogeneity) of all relevant FTIRI variables), we examined biopsies from a matched case-controlled study, in which 60 women with fractures, were each paired with an age-and BMD-matched female control. With the matched data set of 120 women, conditional logistic regression analysis revealed that significant explanatory variables of fracture were decreased carbonate-to-phosphate ratio in both cancellous (Odds Ratio =0.580, 95% confidence interval (CI)=[0.37, 0.909], p= 0.0176) and cortical bone (Odds Ratio= 0.519, 95% CI=[0.325, 0.829], p= 0.0061), and increased heterogeneity (broadened pixel distribution) of collagen maturity for cancellous bone (Odds Ratio = 1.549, 95% CI= [1.002, 2.396], p=0.0491). The observation that collagen maturity was no longer linked to fracture in age-and BMD-matched samples suggests that age-dependent variation in collagen maturity may be a more important contributory factor to fragility fractures than previously thought.