Granke Mathilde, Makowski Alexander J, Uppuganti Sasidhar, Does Mark D, Nyman Jeffry S
Department of Orthopaedic Surgery and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, USA.
Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
J Bone Miner Res. 2015 Jul;30(7):1290-300. doi: 10.1002/jbmr.2452. Epub 2015 Jun 8.
Fracture risk does not solely depend on strength but also on fracture toughness; ie, the ability of bone material to resist crack initiation and propagation. Because resistance to crack growth largely depends on bone properties at the tissue level, including collagen characteristics, current X-ray based assessment tools may not be suitable to identify age-related, disease-related, or treatment-related changes in fracture toughness. To identify useful clinical surrogates that could improve the assessment of fracture resistance, we investigated the potential of (1)H nuclear magnetic resonance spectroscopy (NMR) and reference point indentation (RPI) to explain age-related variance in fracture toughness. Harvested from cadaveric femurs (62 human donors), single-edge notched beam (SENB) specimens of cortical bone underwent fracture toughness testing (R-curve method). NMR-derived bound water showed the strongest correlation with fracture toughness properties (r = 0.63 for crack initiation, r = 0.35 for crack growth, and r = 0.45 for overall fracture toughness; p < 0.01). Multivariate analyses indicated that the age-related decrease in different fracture toughness properties were best explained by a combination of NMR properties including pore water and RPI-derived tissue stiffness with age as a significant covariate (adjusted R(2) = 53.3%, 23.9%, and 35.2% for crack initiation, crack growth, and overall toughness, respectively; p < 0.001). These findings reflect the existence of many contributors to fracture toughness and emphasize the utility of a multimodal assessment of fracture resistance. Exploring the mechanistic origin of fracture toughness, glycation-mediated nonenzymatic collagen crosslinks and intracortical porosity are possible determinants of bone fracture toughness and could explain the sensitivity of NMR to changes in fracture toughness. Assuming fracture toughness is clinically important to the ability of bone to resist fracture, our results suggest that improvements in fracture risk assessment could potentially be achieved by accounting for water distribution (quantitative ultrashort echo time magnetic resonance imaging) and by a local measure of tissue resistance to indentation, RPI.
骨折风险不仅取决于骨骼强度，还取决于骨折韧性，即骨材料抵抗裂纹萌生和扩展的能力。由于对裂纹扩展的抵抗力很大程度上取决于组织水平的骨特性，包括胶原蛋白特性，当前基于X射线的评估工具可能不适用于识别与年龄、疾病或治疗相关的骨折韧性变化。为了确定能够改善骨折抵抗力评估的有用临床替代指标，我们研究了氢核磁共振波谱（NMR）和参考点压痕法（RPI）解释骨折韧性与年龄相关差异的潜力。从尸体股骨（62名人类捐赠者）获取的皮质骨单边缺口梁（SENB）标本进行了骨折韧性测试（R曲线法）。NMR衍生的结合水与骨折韧性特性的相关性最强（裂纹萌生时r = 0.63，裂纹扩展时r = 0.35，整体骨折韧性时r = 0.45；p < 0.01）。多变量分析表明，不同骨折韧性特性与年龄相关的下降最好由包括孔隙水的NMR特性和RPI衍生的组织刚度组合来解释，年龄作为显著协变量（裂纹萌生、裂纹扩展和整体韧性的调整R²分别为53.3%、23.9%和35.2%；p < 0.001）。这些发现反映了骨折韧性存在多种影响因素，并强调了骨折抵抗力多模式评估的实用性。探索骨折韧性的机制起源，糖基化介导的非酶胶原蛋白交联和皮质内孔隙率可能是骨折韧性的决定因素，并且可以解释NMR对骨折韧性变化的敏感性。假设骨折韧性对骨骼抵抗骨折的能力具有临床重要性，我们的结果表明，通过考虑水分布（定量超短回波时间磁共振成像）和通过局部测量组织对压痕的抵抗力（RPI），有可能实现骨折风险评估的改进。
