Wright Quinton, Chiapparelli Erika, Shue Jennifer, Adu Kobby, Han Yi Xin, Sama Andrew A, Girardi Federico P, Cammisa Frank P, Hughes Alexander P, Donnelly Eve
Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, United States.
Department of Orthopedics, Hospital for Special Surgery, New York, NY 10021, United States.
JBMR Plus. 2025 Jun 11;9(9):ziaf100. doi: 10.1093/jbmrpl/ziaf100. eCollection 2025 Sep.
Understanding the aspects of bone that contribute to skeletal integrity is critical to screening and treatment of skeletal diseases, as well as preoperative screening for orthopedic procedures. In bone, collagen organization and structure are significant contributing factors to mechanical integrity. Despite evidence that advanced glycation endproducts (AGEs) alter collagen structure and degrade bone mechanical properties, the relationship between AGE accumulation and collagen organization has not been examined in human bone tissue. In this cohort study, we examined the relationships between fluorescent AGE (fAGE) accumulation, collagen fibril alignment, and collagen fibril density in iliac crest biopsies from men and women undergoing spine fusion surgery ( = 140). We hypothesized that collagen in bone with greater fAGE crosslink density would be less dense and less aligned compared to bone with lower fAGE crosslink density. We quantified the density of fAGEs, collagen thickness/density, and collagen fibril alignment using multiphoton and second harmonic generation microscopy. Trabecular bone with greater values of crosslink density had greater collagen fibril alignment (rho = 0.495, = 7.09·10). The observed correlation between fAGEs and collagen alignment may reflect co-occurring aspects of bone tissue maturation: regions of more mature bone with higher levels of fAGEs may also have high collagen alignment, and regions of newer bone with lower levels of fAGEs may also have disorganized collagen fibrils. Measurement of collagen organization may capture aspects of bone quality that contribute to tissue integrity in clinical populations at risk of surgical complications.
了解对骨骼完整性有贡献的骨骼方面对于骨骼疾病的筛查和治疗以及骨科手术的术前筛查至关重要。在骨骼中，胶原蛋白的组织和结构是影响机械完整性的重要因素。尽管有证据表明晚期糖基化终产物（AGEs）会改变胶原蛋白结构并降低骨骼机械性能，但AGE积累与胶原蛋白组织之间的关系尚未在人体骨组织中进行研究。在这项队列研究中，我们研究了接受脊柱融合手术的男性和女性（n = 140）髂嵴活检中荧光AGE（fAGE）积累、胶原纤维排列和胶原纤维密度之间的关系。我们假设，与fAGE交联密度较低的骨骼相比，fAGE交联密度较高的骨骼中的胶原蛋白密度更低且排列更不规则。我们使用多光子和二次谐波产生显微镜对fAGEs的密度、胶原厚度/密度和胶原纤维排列进行了量化。交联密度值较高的小梁骨具有更高的胶原纤维排列（rho = 0.495，p = 7.09·10）。观察到的fAGEs与胶原蛋白排列之间的相关性可能反映了骨组织成熟的共同方面：fAGEs水平较高的更成熟骨区域可能也具有高胶原蛋白排列，而fAGEs水平较低的较新骨区域可能也具有无序的胶原纤维。胶原蛋白组织的测量可能捕捉到对有手术并发症风险的临床人群中有助于组织完整性的骨质量方面。
