Greater collagen alignment is associated with accumulation of advanced glycation endproducts in iliac trabecular bone in men and women undergoing spine fusion surgery.

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 (n = 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, p = 7.09·10-9). 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.