Bone collagen network integrity and transverse fracture toughness of human cortical bone.
Bone collagen network integrity and transverse fracture toughness of human cortical bone.
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DOI：
10.1016/j.bone.2018.10.024
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发表时间：
2019-03
期刊：
影响因子：
4.1
通讯作者：
Nyman JS
中科院分区：
文献类型：
--
作者：
Willett TL;Dapaah DY;Uppuganti S;Granke M;Nyman JS
由于骨骼影响疾病和骨折给经济、社会和卫生保健系统带来巨大负担，因此迫切需要对骨骼脆弱性的决定因素有更深入的了解。骨是一种由i型胶原蛋白和非化学计量羟基磷灰石组成的复杂分层复合物，其韧性来源于其有机相。在这项研究中，我们测试了早期观察到的通过热机械方法测量的骨胶原完整性与骨折工作之间的强相关性是否存在于更普遍和异质性的人群样本中。邻近的均匀标本来自一个已建立的、高度表征的和先前发表的人类皮质骨样本（股骨中轴），在EDTA中脱钙。最初的62名捐赠者中有54人被纳入其中（26名男性和28名女性，年龄在21 -101岁之间，衰老，骨质疏松症，糖尿病和癌症）。脱钙后，对骨胶原进行热液等距张力（HIT）测试，测量胶原的热稳定性（变性温度，Td）和网络连通性（最大等距张力产生速率，Max.Slope）。我们使用线性回归和带有几个解释变量的一般线性模型（GLMs）来确定HIT参数与普遍接受的骨质量因素（如皮质孔隙度、戊sidine含量[pen]、吡啶啉含量[pyd]）、年龄和断裂韧性测量（裂纹起裂韧性，Kinit，以及在不稳定快速骨折点评估的总能量释放/耗散率，J-int）之间的关系是否显著。骨胶原连通性（Max.Slope）与断裂韧性（R2=24-35%）相关良好，与结合水分数（BW, R2=7.9%）和孔隙水分数（PW, R2=9.1%）相关程度较低。未检测到与年龄、表观体积骨密度（vBMD）、成熟酶[pyd]和非酶胶原交联[pen]的显著相关性。glm发现Max。斜率和vBMD（或BW），有或没有年龄作为额外的协变量，都显著解释了Kinit的方差（调整后的r2 =36.7-49.0%）。此外，J-int的最佳拟合模型（调整后r2 =35.7%）仅包括年龄和Max。斜率作为Max的解释变量。坡度的贡献是年龄的两倍。Max。坡度和无年龄的体重也是J-int的显著预测因子（调整r2 =35.5%）。综上所述，用热力学方法测量的骨胶原完整性是影响皮质骨断裂韧性的关键因素。这项研究进一步表明，在寻求理解衰老和疾病导致的骨折率升高时，应该更多地关注整体有机相的降解，而不是特定的生物标志物（例如[pen]）。
Greater understanding of the determinants of skeletal fragility is highly sought due to the great burden that bone affecting diseases and fractures have on economies, societies and health care systems. Being a complex, hierarchical composite of collagen type-I and non-stoichiometric substituted hydroxyapatite, bone derives toughness from its organic phase. In this study, we tested whether early observations that a strong correlation between bone collagen integrity measured by thermomechanical methods and work to fracture exist in a more general and heterogeneous sampling of the population. Neighboring uniform specimens from an established, highly characterized and previously published collection of human cortical bone samples (femur mid-shaft) were decalcified in EDTA. Fifty-four of the original 62 donors were included (26 male and 28 females; ages 21 -101 years; aging, osteoporosis, diabetes and cancer). Following decalcification, bone collagen was tested using hydrothermal isometric tension (HIT) testing in order to measure the collagen’s thermal stability (denaturation temperature, Td) and network connectivity (maximum rate of isometric tension generation; Max.Slope). We used linear regression and general linear models (GLMs) with several explanatory variables to determine whether relationships between HIT parameters and generally accepted bone quality factors (e.g., cortical porosity, pentosidine content [pen], pyridinoline content [pyd]), age, and measures of fracture toughness (crack initiation fracture toughness, Kinit, and total energy release/dissipation rate evaluated at the point of unstable fast fracture, J-int) were significant. Bone collagen connectivity (Max.Slope) correlated well with the measures of fracture toughness (R2=24-35%), and to a lesser degree with bound water fraction (BW; R2=7.9%) and pore water fraction (PW; R2=9.1%). Significant correlations with age, apparent volumetric bone mineral density (vBMD), and mature enzymatic [pyd] and non-enzymatic collagen crosslinks [pen] were not detected. GLMs found that Max.Slope and vBMD (or BW), with or without age as additional covariate, all significantly explained the variance in Kinit (adjusted-R2=36.7-49.0%). Also, the best-fit model for J-int (adjusted-R2=35.7%) included only age and Max.Slope as explanatory variables with Max.Slope contributing twice as much as age. Max.Slope and BW without age were also significant predictors of J-int (adjusted-R2=35.5%). In conclusion, bone collagen integrity as measured by thermomechanical methods is a key factor in cortical bone fracture toughness. This study further demonstrates that greater attention should be paid to degradation of the overall organic phase, rather than a specific biomarker (e.g. [pen]), when seeking to understand elevated fracture rates in aging and disease.
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影响因子：
3.3
作者：
Besdo S;Vashishth D
通讯作者：
Vashishth D
影响因子：
4.1
作者：
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Mitton, David
DOI：
10.1016/j.jmbbm.2015.08.012
发表时间：
2015-12
影响因子：
3.9
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
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