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Urinary CTX-II, Serum MMP-3 And Serum PIIANP Following Anterior Cruciate Ligament Reconstruction: A Pilot Study

Urinary CTX-II, Serum MMP-3 And Serum PIIANP Following Anterior Cruciate Ligament Reconstruction: A Pilot Study

Lachlan Batty, FRACS, AUSTRALIA Julian A. Feller, FRACS, FAOrthA, AUSTRALIA Timothy S. Whitehead, MBBS, FRACS, AUSTRALIA Brian M. Devitt, MD, PhD, FRCS, FRACS, IRELAND Kate E. Webster, PhD, AUSTRALIA

OrthoSport Victoria Research Unit, Melbourne, Victoria, AUSTRALIA


2023 Congress   ePoster Presentation   2023 Congress   Not yet rated

 

Diagnosis / Condition

Patient Populations

Anatomic Location

Anatomic Structure

Ligaments

ACL


Summary: Urinary and serum biomarkers after anterior cruciate ligament reconstruction


Background

Changes in the levels of urinary and serum biomarkers of chondral metabolism have been identified after anterior cruciate ligament (ACL) injury and reconstruction. These markers may hold value in identifying patients at risk of premature osteoarthritis (OA).

Hypothesis/Purpose: To measure trends in three biomarkers with potential clinical value during the first year following ACL reconstruction. To evaluate any association between biomarker levels and age or body mass index (BMI).

Methods

Twenty-two ACL injured patients from a longitudinal cohort study were included (mean age 25.2 (SD 8.0) years; 12 (54.5%) male). Urine and serum samples were taken at the time of primary ACL reconstruction and at the 6 and 12 months post operative timepoints. Levels of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum Matrix Metalloproteinase 3 (MMP-3) and serum N-propeptide of collagen IIA (PIIANP) were measured using commercially available enzyme-linked immunosorbent assays (ELISA). CTX-II levels were normalized to urinary creatinine levels and initial testing with the CloudClone® ELISA. CTX-II levels were retested with a second commercially available ELISA (CartiLaps®) as the initial testing results differed from the anticipated levels.

Results

Measured levels of CTX-II differed significantly between the 2 assays at each timepoint (p<0.01 for all timepoints). Levels of CTX-II using the CartiLaps® Assay decreased over time; however, this was not statistically significant (F (2, 38) = 1.29, p=0.29, eta2 = 0.64). Whereas levels of CTX-II when using the CloudClone Assay significantly increased over the measured timepoints (F (2,40) = 3.7, p=0.03, eta2 = 0.16). Levels of MMP3 significantly increased over the measured timepoints (F (2,40) = 3.34, p=0.046, eta2 = 0.14). Levels of PIIANP significantly increased over the measured timepoints (F (2,42) = 12.83, p<0.001, eta2 = 0.38). With the CartiLaps® Assay there was a significant negative correlation between patient age and CTX-II levels at baseline (r= -0.66, p=0.001), 6 months (r=-0.56, p=0.008) and 12 months (r= -0.61, p=0.004).There were no other associations between biomarker levels and age or BMI at any time point.

Conclusion

The assay used is relevant to the levels and trends of CTX-II, with levels either decreasing or increasing with time depending upon the assay used. There was a negative association between CTX-II levels and patient age on one assay. Levels of MMP-3 and PIIANP increase during the first year following ACLR.

Clinical Relevance: Changes in biomarker levels can be seen during the first year following ACLR. These measurements may provide insight into changes occurring in the knee at the cellular level. Future work should aim to identify if these markers have a role in predicting patients at risk of premature OA, before clinical and radiological signs become apparent.


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