Biomarkers for Preoperative Bone Quality Assessment: A Prospective Investigation of Dermal Ultrasound and Advanced Glycation End-products in Lumbar Fusion Patients

Collagen type I is a fundamental component of bone, tendons, ligaments, and skin. Its quality influences tissue strength, and impaired collagen cross-linking, such as advanced glycation end products (AGEs), compromises bone quality and surgical outcomes. While bone AGEs can be quantified from biopsies, this is impractical preoperatively. Dermal ultrasound (US) offers a non-invasive method to assess collagen integrity. Prior work linked skin US parameters to AGEs, but their relationship with second harmonic generation (SHG) imaging, which provides detailed information on bone collagen architecture, remains unclear. This study investigated correlations between dermal US and SHG-derived collagen parameters in lumbar fusion patients.

A single-center, cross-sectional analysis was performed in patients undergoing lumbar fusion (2014-2021) with preoperative dermal US and intraoperative iliac crest bone biopsy. US echogenicity was measured at average dermal (AD), upper dermal (UD), and lower dermal (LD) layers. SHG microscopy of biopsies quantified collagen crosslink density, fibril alignment, ellipticity, and homogeneity in cortical and trabecular bone. Associations between US and SHG parameters were tested using regression models adjusted for age, sex, BMI, and diabetes.

Of 184 patients, 136 were analyzed (50.9% female, median age 62.2 years). Females exhibited higher US echogenicity across dermal layers (p < 0.001), though SHG findings did not differ by sex. Multivariable regression showed LD echogenicity significantly predicted collagen crosslink density in cortical (p = 0.040) and trabecular bone (p = 0.013). No significant associations were observed for AD or UD.

Dermal US, particularly LD echogenicity, correlates with bone collagen crosslink density, supporting its potential as a non-invasive biomarker of bone quality in lumbar fusion patients.