Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Department of Orthopaedic Surgery and Bioengineering. University of Michigan, Ann Arbor, MI, USA.
Appl Spectrosc. 2022 Apr;76(4):416-427. doi: 10.1177/00037028211055477. Epub 2021 Dec 2.
Applications of vibrational spectroscopy to assess bone disease and therapeutic interventions are continually advancing, with tissue mineral and protein composition frequently investigated. Here, we used two spectroscopic approaches for determining bone composition in a mouse model () of the brittle bone disease osteogenesis imperfecta (OI) with and without antiresorptive agent treatment (alendronate, or ALN, and RANK-Fc). Near-infrared (NIR) spectral analysis using a fiber optic probe and attenuated total reflection Fourier transform infrared spectroscopy (ATR FTIR) mode were applied to investigate bone composition, including water, mineral, and protein content. Spectral parameters revealed differences among the control wildtype (WT) and OIM groups. NIR spectral analysis of protein and water showed that OIM mouse humerii had ∼50% lower protein and ∼50% higher overall water content compared to WT bone. Moreover, some OIM-treated groups showed a reduction in bone water compared to OIM controls, approximating values observed in WT bone. Differences in bone quality based on increased mineral content and reduced carbonate content were also found between some groups of treated OIM and WT bone, but crystallinity did not differ among all groups. The spectroscopically determined parameters were evaluated for correlations with gold-standard mechanical testing values to gain insight into how composition influenced bone strength. As expected, bone mechanical strength parameters were consistently up to threefold greater in WT mice compared to OIM groups, except for stiffness in the ALN-treated OIM groups. Furthermore, bone stiffness, maximum load, and post-yield displacement showed the strongest correlations with NIR-determined protein content (positive correlations) and bound-water content (negative correlations). These results demonstrate that in this study, NIR spectral parameters were more sensitive to bone composition differences than ATR parameters, highlighting the potential of this nondestructive approach for screening of bone diseases and therapeutic efficacy in pre-clinical models.
振动光谱学在评估骨骼疾病和治疗干预方面的应用不断发展，经常研究组织矿物质和蛋白质组成。在这里，我们使用两种光谱方法来确定成骨不全症（OI）脆性骨病小鼠模型（）和抗吸收剂治疗（阿仑膦酸钠或 ALN 和 RANK-Fc）的骨骼组成。使用光纤探头的近红外（NIR）光谱分析和衰减全反射傅里叶变换红外光谱（ATR FTIR）模式用于研究骨组成，包括水、矿物质和蛋白质含量。光谱参数揭示了对照组野生型（WT）和 OIM 组之间的差异。NIR 光谱分析蛋白质和水表明，与 WT 骨相比，OIM 鼠标肱骨的蛋白质含量低约 50%，总水含量高约 50%。此外，与 OIM 对照组相比，一些 OIM 治疗组的骨水减少，接近 WT 骨的观察值。还发现一些治疗 OIM 和 WT 骨之间基于矿物质含量增加和碳酸盐含量减少的骨质量差异，但所有组的结晶度没有差异。还评估了光谱确定的参数与金标准机械测试值的相关性，以深入了解组成如何影响骨强度。正如预期的那样，与 OIM 组相比，WT 小鼠的骨机械强度参数一致高 3 倍，除了 ALN 治疗的 OIM 组的刚度。此外，骨刚度、最大载荷和屈服后位移与 NIR 测定的蛋白质含量（正相关）和结合水含量（负相关）显示出最强的相关性。这些结果表明，在这项研究中，NIR 光谱参数比 ATR 参数更能敏感地反映骨骼组成差异，突出了这种非破坏性方法在临床前模型中筛选骨骼疾病和治疗效果的潜力。
