A novel approach for longitudinal analysis of serum biomarkers of joint metabolism and knee injury in military officers

by Liubov Arbeeva, Virginia B. Kraus, Amanda E. Nelson, Maryalice Nocera, Leigh F. Callahan, Richard F. Loeser, Kenneth L. Cameron, Jesse R. Trump, Stephen W. Marshall, Yvonne M. Golightly

To investigate the longitudinal relationships between serum biomarkers of joint metabolism, knee injury, and Knee Injury and Osteoarthritis Outcome Score (KOOS) using novel methodologies.

Data were collected from military officers who enrolled as cadets between 2004–2009, with follow-up conducted between 2015–2017. Analyses included 234 officers who had no history of knee ligament/meniscal injury at the time of military academy matriculation, had serum biomarker measurements at matriculation and graduation, demographic data, and KOOS assessment at follow-up. Biomarkers included Collagen Type II (C2C) and Type I and II (C1,2C) collagenase-generated cleavage epitopes, C-terminal propeptide of Type II collagen (CPII), and C- and N-terminal telopeptides of type I collagen (CTX and NTX). Angle-based Joint and Individual Variation Explained (AJIVE) was used to determine demographic determinants of biomarker levels and individual modes of variation specific to biomarker levels at matriculation and graduation, stratified by sex.

We confirmed known associations of joint metabolism biomarkers with age in both sexes and with smoking in males. Matriculation biomarker data in males suggested a protective biomarker profile characterized by high cartilage synthesis and low cleavage of type I and II collagen in association with healthy KOOS scores at follow-up. CPII measured at matriculation was negatively associated with incident injuries after adjustment for smoking status (p = 0.03, logistic regression), confirming results from AJIVE.

These exploratory analyses suggest that CPII alone, or in combination with other joint metabolism biomarkers, may help identify individual risk of knee injury.