Ligamentum flavum: changes in vascular density, physical and histopathobiochemical properties in lumbar spine based on anatomical localization, spinal segment levels, and presence of lumbar spinal stenosis

Background

Hypertrophy of the ligamentum flavum (LF) contributes significantly to the development of lumbar spinal stenosis (LSS), a serious and often disabling disease predominantly affecting the aging population. Histologic changes in the ligament and the tissue mediators that drive these alterations have been described, but their spatial distribution within the ligament remains unclear. Understanding these changes may enable future interventions to slow ligament degeneration and disease progression. To date, no study has comprehensively described the distribution of pathological changes within individual ligaments.

Methods

This study combined histopathobiochemical analysis and micromechanical mapping of healthy and degenerated human LF specimens obtained perioperatively from 57 patients undergoing lumbar spine surgery (38 with LSS and 19 controls). Ligament samples were analyzed histologically for vascular density, presence of inflammatory infiltrates, and chondroid metaplasia using morphometric software and immunohistochemical staining. Mechanical properties, including stiffness (Young’s modulus) and contact pressure, were measured via nanoindentation using the Hysitron BioSoft In-Situ Indenter system. Samples were spatially mapped across 9 anatomical zones of the LF to investigate regional variation. Statistical analyses compared these parameters between spinal segments (L3/4, L4/5, L5/S1), between LSS and control groups, and evaluated age-related trends.

Results

The central region of the LF exhibited significantly higher vascularity and stiffness compared to peripheral regions. Areas showing chondroid metaplasia and inflammation demonstrated increased vascularization, characteristic of LSS pathology. Although vascular density and mechanical stiffness were elevated in LSS patients versus controls, these differences did not reach statistical significance. Age-related trends differed between groups: stiffness increased with age in controls but decreased in LSS patients.

Conclusions

The greatest changes in vascularization and stiffness occur in the central region of ligamentum flavum. Understanding these localized alterations may support future development of targeted therapies to slow or prevent disease progression.