2025 ISAKOS Congress in Munich, Germany

2025 ISAKOS Biennial Congress Paper


Trends and Predictors of Systemic Biomarkers of Chondral Metabolism in the First Year After Anterior Cruciate Ligament Reconstruction

Lachlan Batty, FRACS, Melbourne, VIC AUSTRALIA
Kate E. Webster, PhD, Bundoora, Victoria AUSTRALIA
Minh Huynh, PhD, Melbourne, Victoria AUSTRALIA
Natasha Vasileff, PhD, Canberra, ACT AUSTRALIA
Jereme Spiers, PhD, Canberra AUSTRALIA
Brian M. Devitt, MD, PhD, FRCS, FRACS, Dublin, Leinster IRELAND
Timothy S. Whitehead, MBBS, FRACS, Richmond, VIC AUSTRALIA
Haydn Klemm, BFSc&Nutr (Hons), Richmond, VIC AUSTRALIA
Julian A. Feller, FRACS, FAOrthA, Melbourne, VIC AUSTRALIA

OrthoSport Victoria, Melbourne, Victoria, AUSTRALIA

FDA Status Not Applicable

Summary

Urinary and serum biomarkers of chondral metabolism show significant changes in the first year after ACL reconstruction and patient factors explain variability in these biomarkers.

Abstract

Background

Anterior cruciate ligament (ACL) injuries and reconstruction are associated with alterations in chondral homeostasis and post traumatic osteoarthritis. Biomarkers of chondral metabolism may have a role in quantitatively evaluating this phenomenon.

Purpose

To describe changes in 3 systemic biomarkers of chondral metabolism during the first year after ACL reconstruction. To identify factors associated with biomarker concentrations at baseline and at the 12-month post operative timepoint.

Methods

From a prospective longitudinal study, urine and serum samples were taken immediately prior to primary ACL reconstruction and at 6- and 12-months post operatively. 666 patients provided samples (mean age 24.9 years (SD 7.2), 60.5% male, mean pre-injury Marx score 12.3 (SD 4.0)). Concentrations of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of type 2 collagen degradation, serum N-propeptide of collagen IIA (PIIANP), a marker of type 2 collagen synthesis and serum Matrix Metalloproteinase 3 (MMP-3), a mediator in chondral matrix degradation were measured using immunoassays. Linear mixed modelling and machine learning statistical techniques were employed for data analysis with explanatory and predictive models created.

Results

CTX-II concentrations decreased by 25% (95%CI 30 - 20%) from baseline to 6-months, and 27% (95%CI 41 - 23%) from baseline to 12 months (p<0.001). PIIANP increased by 40% (95%CI 35-46%) and 42% (95%CI 36 - 48%) from baseline to 6-months, and baseline to 12-months, respectively (p<0.001). MMP-3 increased by 35% (95%CI 21 - 51%) and 44% (95%CI 29 - 61%) from baseline to 6 months, and baseline to 12 months respectively (p<0.001). In order of hierarchy, age, sex, and body mass index (BMI) were the three most important variables for predicting baseline CTX-II concentrations. Age, BMI, and time from injury to surgery were most important in predicting baseline PIIANP concentrations. BMI, age and articular cartilage status at surgery were the most important in predicting baseline MMP3 concentrations. At the 12-month time point, Age, Sex and the 12-month Marx score were the most important factors in predicting CTX-II concentrations. Age, BMI and 12-month Marx score were most important in predicting PIIANP concentrations. Age, Sex and 12 Month Marx score were most important in predicting MMP-3 concentrations.

Conclusion

Reducing urinary CTX-II levels coupled with increasing serum PIIANP levels, (indicating reduced type 2 collagen degradation and increasing type 2 collagen synthesis respectively), is suggestive of a reparative chondral response in the first year following ACL injury and reconstruction. Predominantly non-modifiable demographic, surgical, and anatomic factors are important in predicting baseline and 12-month concentrations of the three biomarkers.