Osteosarcopenia in the Spine Beyond Bone Mineral Density: Association Between Paraspinal Muscle Impairment and Advanced Glycation Endproducts.

Abstract

Prospective cross-sectional study. To determine if an accumulation of advanced glycation endproducts (AGEs) is associated with impaired paraspinal muscle composition. Impaired bone integrity and muscle function are described as osteosarcopenia. Osteosarcopenia is associated with falls, fragility fractures, and reduced quality of life. Bone integrity is influenced by bone quantity (bone mineral density) and quality (microarchitecture and collagen). The accumulation of AGEs stiffens collagen fibers and increases bone fragility. The relationship between paraspinal muscle composition and bone collagen properties has not been evaluated. Intraoperative bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton microscopy for fluorescent AGE cross-link density (fAGEs). Preoperative magnetic resonance imaging measurements at level L4 included the musculus (m.) psoas and combined m. multifidus and m. erector spinae (posterior paraspinal musculature, PPM). Muscle segmentation on axial images (cross-sectional area, CSA) and calculation of a pixel intensity threshold method to differentiate muscle (functional cross-sectional area, fCSA) and intramuscular fat (FAT). Quantitative computed tomography was performed at the lumbar spine. Univariate and multivariable regression models were used to investigate associations between fAGEs and paraspinal musculature. One hundred seven prospectively enrolled patients (50.5% female, age 60.7y, BMI 28.9kg/m 2 ) were analyzed. In all, 41.1% and 15.0% of the patients demonstrated osteopenia and osteoporosis, respectively. Univariate linear regression analysis demonstrated a significant association between cortical fAGEs and CSA in the psoas (ρ=0.220, P =0.039) but not in the PPM. Trabecular fAGEs revealed no significant associations to PPM or psoas musculature. In the multivariable analysis, higher cortical fAGEs were associated with increased FAT (β=1.556; P =0.002) and CSA (β=1.305; P =0.005) in the PPM after adjusting for covariates. This is the first investigation demonstrating that an accumulation of nonenzymatic collagen cross-linking product fAGEs in cortical bone is associated with increased intramuscular fat in the lumbar paraspinal musculature.