Boskey Adele L, Donnelly Eve, Boskey Elizabeth, Spevak Lyudmila, Ma Yan, Zhang Wei, Lappe Joan, Recker Robert R
Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA.
Materials Science and Engineering Department, Cornell University, Ithaca, NY, USA.
J Bone Miner Res. 2016 May;31(5):1070-81. doi: 10.1002/jbmr.2759. Epub 2015 Dec 24.
Fourier transform infrared imaging (FTIRI) provides information on spatial distribution of the chemical composition of thin tissue specimens at ∼7 µm spatial resolution. This study of 120 age- and bone mineral density (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 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 was observed, validating the pairing scheme. Our first study of unmatched 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 analyses revealed that significant explanatory variables of fracture were decreased carbonate-to-phosphate ratio in both cancellous (odds ratio [OR] = 0.580, 95% confidence interval [CI] 0.37-0.909, p = 0.0176) and cortical bone (OR = 0.519, 95% CI 0.325-0.829, p = 0.0061), and increased heterogeneity (broadened pixel distribution) of collagen maturity for cancellous bone (OR = 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. © 2015 American Society for Bone and Mineral Research.
傅里叶变换红外成像(FTIRI)能以约7微米的空间分辨率提供薄组织标本化学成分空间分布的信息。这项针对120名年龄和骨矿物质密度(BMD)匹配患者的研究旨在调查在髂嵴活检中测量的FTIRI变量与任何部位脆性骨折之间的关联。一项对54名女性的早期研究发现,髋部BMD是皮质骨骨折风险的重要解释变量,但不是松质骨骨折风险的重要解释变量。在本研究中,通过匹配控制了年龄和BMD,未观察到此类关联,验证了配对方案。我们对未匹配的髂嵴活检的首次研究发现,当与其他协变量结合时,胶原蛋白成熟度(松质骨和皮质骨)增加以及矿物质晶体大小(仅皮质骨)增加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、碳酸盐与磷酸盐比率以及所有相关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中的活检样本,其中60名骨折女性分别与一名年龄和BMD匹配的女性对照配对。利用这120名女性的匹配数据集,条件逻辑回归分析显示,骨折的重要解释变量包括松质骨(优势比[OR]=0.580,95%置信区间[CI]0.37 - 0.909,p = 0.0176)和皮质骨(OR = 0.519,95%CI 0.325 - 0.829,p = 0.0061)中碳酸盐与磷酸盐比率降低,以及松质骨胶原蛋白成熟度异质性增加(像素分布变宽)(OR = 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比先前认为的更重要的促成因素。©2015美国骨与矿物质研究学会。