Insulin Resistance as a Risk Factor for Flavum Hypertrophy in Lumbar Spinal Stenosis

Abstract

Introduction: Ligamentum flavum (LF) hypertrophy is the main etiological factor in the development of lumbar spinal stenosis (LSS); however, its molecular pathology remains unclear. Histologically, LF hypertrophy is characterized by a reduction in elastic fibers and an increase in collagen fibers. We previously performed miRNA transcriptomic analysis on excised LF from elderly patients with LSS and identified the insulin receptor signaling along with TGFβ-mediated signaling as pathways involved in ligament hypertrophy. Therefore, this study aimed to investigate the involvement of endogenous insulin as a risk factor for LF hypertrophy in patients with LSS. Methods: A total of 1,119 patients aged 65 years (average: 76.1±5.9 years) treated for LSS including surgery and conservative treatment were analyzed. The flavum canal ratio (FCR) was calculated in the MRI cross-sectional image, and an FCR of 0.4275 or greater was defined as ligamentous stenosis according to Sakai's criteria. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated and values 2.5 were indicative of insulin resistance in Japanese people. Results: Fifty-one percent of patients with LSS exhibited LF hypertrophy, correlating with higher age, proportion of males and diabetic patients, BMI, HOMA-IR, and creatinine. Among LSS patients, 43.0% had insulin resistance, with 47.1% exhibiting LF hypertrophy and 38.6% without LF hypertrophy, with a significant difference (p<0.01). LSS patients with high insulin resistance also demonstrated significantly higher FCR (p<0.05) and a higher percentage of LF hypertrophy (p<0.01). Conditional logistic regression analysis, adjusting for age, identified HOMA-IR as a significant factor. Conclusions: The study establishes an association between LF hypertrophy and insulin resistance. Considering LF hypertrophy as an inflammation-triggered degeneration of elastic fibers, age-related changes in LF may underlie the basis of inflammatory aging.

Keywords

• lumbar spinal stenosis
• ligamentum flavum
• insulin resistance
• pathology