2025 ISAKOS Congress in Munich, Germany

2025 ISAKOS Biennial Congress Paper


Correlation Between Serum Biomarkers and Early Articular Cartilage Degradation Reported by Magnetic Resonance Imaging After Anterior Cruciate Ligament Reconstruction

Andrew Minchow, BS UNITED STATES
Matthew Tao, MD, Omaha, NE UNITED STATES
Balasrinivasa Sajja, PhD, Omaha, NE UNITED STATES
Melissa Manzer, MD, Omaha, NE UNITED STATES
Elizabeth Wellsandt, DPT, PhD, Omaha, NE UNITED STATES

University of Nebraska Medical Center, Omaha, NE, UNITED STATES

FDA Status Not Applicable

Summary

Serum cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-3 (MMP-3), and type I collagen N-telopeptide (NTX) quantities prior to and 6 months after anterior cruciate ligament reconstruction (ACLR) are not correlated with cartilage degradation associated with early osteoarthritis (OA) as defined by percent change in articular cartilage T2 relaxation times.

Abstract

Objectives
Cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-3 (MMP-3), and type I collagen N-telopeptide (NTX) have each been demonstrated to be clinically relevant biomarkers of bone and cartilage breakdown and resorption. An increase in T2 relaxation time in articular cartilage on magnetic resonance imaging (MRI) is a validated measure of signs consistent with early osteoarthritis (OA) progression. This study evaluated the relationship between key serum biomarkers (COMP, MMP-3, and NTX), knee cartilage T2 relaxation time, and concomitant meniscus injury within the first six months after ACL reconstruction (ACLR).

Methods

This study was a secondary analysis of a prospective cohort study of individuals between 15 and 35 years of age within 1 month of ACL injury (pre-ACLR). Serum samples were collected at pre-ACLR and 6 months after ACLR. Serum COMP, MMP-3, NTX were quantified using enzyme-linked immunosorbent assay kits. A non-contrast 3T MRI of the injured knee was performed pre-ACLR and 6 months after ACLR. Femoral, tibial, and patellar cartilage for each MRI slice of the injured knee was manually segmented. Cartilage regions were defined by 1) the medial and lateral tibiofemoral compartments, and 2) the tibiofemoral weightbearing (WB) regions between the farthest edges of the anterior and posterior meniscus horns. The trochlear and patellar cartilage regions were each defined by a single region. T2 relaxation time was analyzed within six masked knee cartilage regions: medial femoral condyle (MFC) WB, medial tibial condyle (MTC) WB, lateral femoral condyle (LFC) WB, lateral tibial condyle (LTC) WB, trochlea, and patella. Concomitant knee injuries were identified via an arthroscopic assessment during ACLR and recorded after review of operative reports.

Results

Thirty-two patients were included (mean age:18.9, 62.5% female, mean body mass index, BMI:25.0). COMP and MMP-3 increased (10.3% and 18.3%, respectively) from pre-ACLR to 6 months after ACLR, while NTX decreased (-17.63%) over the same time frame. T2 relaxation times for all cartilage regions increased (worsened) from pre-ACLR to 6 months after ACLR (range:3.47%-9.01%). There were no significant correlations between any of the serum biomarkers and percent change in T2 relaxation from pre-ACLR to 6 months after ACLR (p>0.05). After adjusting for BMI and age, there was a significant relationship between percent change in NTX from pre-ACLR to 6 months after ACLR and T2 relaxation times from the LFC WB region (ΔR2:0.192, p=0.013), while all other associations remained insignificant (p>0.05). There were no differences in serum biomarkers or cartilage T2 relaxation times for any cartilage region between study participants with and without concomitant medial, lateral, or any meniscal tear (p>0.05).

Conclusion

Serum COMP, MMP-3, and NTX quantities pre-ACLR and 6 months after ACLR were not associated with early signs of cartilage degradation as defined by T2 relaxation time. More severe knee injury as reported by concomitant meniscal tears did not result in significantly different serum biomarker levels or T2 relaxation times within the first 6 months after ACLR. Quantification of serum COMP, MMP-3, and NTX is not a viable substitute for quantitative MRI measures in the assessment of early OA associated cartilage changes after ACLR.