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An Anterior Cruciate Ligament Rupture Increases Levels of Urine N-terminal Cross-linked Telopeptide of Type I Collagen, Urine C-terminal Cross-linked Telopeptide of Type II Collagen, Serum Aggrecan ARGS Neoepitope, and Serum Tumor Necrosis Factor–α

Hagemans, Frans J.A. LU ; Larsson, Staffan LU orcid ; Reijman, Max ; Frobell, Richard B. LU ; Struglics, Andre LU and Meuffels, Duncan E. (2021) In American Journal of Sports Medicine 49(13). p.3534-3543
Abstract

Background: An anterior cruciate ligament (ACL) rupture results in an increased risk of developing knee osteoarthritis (OA) at an early age. Before clinical signs become apparent, the OA process has already been initiated. Therefore, it is important to look at the cascade of changes, such as the activity of cytokines and proteases, which might be associated with the later development of OA. Purpose: To compare biomarker levels in patients with a recent ACL rupture with those in controls with a healthy knee and to monitor biomarker levels over 2 years after an ACL rupture. Study Design: Descriptive laboratory study. Methods: Patients were enrolled after an ACL tear was identified. Serum and urine samples were collected at the time of... (More)

Background: An anterior cruciate ligament (ACL) rupture results in an increased risk of developing knee osteoarthritis (OA) at an early age. Before clinical signs become apparent, the OA process has already been initiated. Therefore, it is important to look at the cascade of changes, such as the activity of cytokines and proteases, which might be associated with the later development of OA. Purpose: To compare biomarker levels in patients with a recent ACL rupture with those in controls with a healthy knee and to monitor biomarker levels over 2 years after an ACL rupture. Study Design: Descriptive laboratory study. Methods: Patients were enrolled after an ACL tear was identified. Serum and urine samples were collected at the time of enrollment in the study (3-25 weeks after the injury) and then at 14 and 27 months after the injury between January 2009 and November 2010. Reference samples were obtained from participants with healthy knees. The following biomarkers were measured with immunological assays: aggrecan ARGS neoepitope (ARGS-aggrecan), tumor necrosis factor–α (TNF-α), interferon-γ, interleukin (IL)–8, IL-10, IL-13, N-terminal cross-linked telopeptide of type I collagen (NTX-I), and C-terminal cross-linked telopeptide of type II collagen (CTX-II). Results: Samples were collected from 152 patients with an acute ACL rupture, who had a median age of 25 years (interquartile range [IQR], 21-32 years). There were 62 urine reference samples (median age, 25 years [IQR, 22-36 years]) and 26 serum reference samples (median age, 35 years [IQR, 24-39 years]). At a median of 11 weeks (IQR, 7-17 weeks) after trauma, serum levels of both ARGS-aggrecan and TNF-α were elevated 1.5-fold (P <.001) compared with reference samples and showed a time-dependent decrease during follow-up. Urine NTX-I and CTX-II concentrations were elevated in an early phase after trauma (1.3-fold [P <.001] and 3.7-fold [P <.001], respectively) compared with reference samples, and CTX-II levels remained elevated compared with reference samples at 2-year follow-up. Strong correlations were found between serum ARGS-aggrecan, urinary NTX-I, and urinary CTX-II (rs = 0.57-0.68). Conclusion: In the first few months after an ACL injury, there was a measurable increase in serum levels of ARGS-aggrecan and TNF-α as well as urine levels of NTX-I and CTX-II. These markers remained high compared with those of controls with healthy knees at 2-year follow-up.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ACL injury, aggrecan, biomarkers, CTX-II, NTX-I, TNF-α
in
American Journal of Sports Medicine
volume
49
issue
13
pages
3534 - 3543
publisher
SAGE Publications
external identifiers
  • pmid:34591687
  • scopus:85116344912
ISSN
0363-5465
DOI
10.1177/03635465211042310
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021 The Author(s).
id
3cd62a4f-da18-4ad6-85a7-e55479b8f87b
date added to LUP
2021-11-01 13:44:19
date last changed
2024-03-23 12:48:27
@article{3cd62a4f-da18-4ad6-85a7-e55479b8f87b,
  abstract     = {{<p>Background: An anterior cruciate ligament (ACL) rupture results in an increased risk of developing knee osteoarthritis (OA) at an early age. Before clinical signs become apparent, the OA process has already been initiated. Therefore, it is important to look at the cascade of changes, such as the activity of cytokines and proteases, which might be associated with the later development of OA. Purpose: To compare biomarker levels in patients with a recent ACL rupture with those in controls with a healthy knee and to monitor biomarker levels over 2 years after an ACL rupture. Study Design: Descriptive laboratory study. Methods: Patients were enrolled after an ACL tear was identified. Serum and urine samples were collected at the time of enrollment in the study (3-25 weeks after the injury) and then at 14 and 27 months after the injury between January 2009 and November 2010. Reference samples were obtained from participants with healthy knees. The following biomarkers were measured with immunological assays: aggrecan ARGS neoepitope (ARGS-aggrecan), tumor necrosis factor–α (TNF-α), interferon-γ, interleukin (IL)–8, IL-10, IL-13, N-terminal cross-linked telopeptide of type I collagen (NTX-I), and C-terminal cross-linked telopeptide of type II collagen (CTX-II). Results: Samples were collected from 152 patients with an acute ACL rupture, who had a median age of 25 years (interquartile range [IQR], 21-32 years). There were 62 urine reference samples (median age, 25 years [IQR, 22-36 years]) and 26 serum reference samples (median age, 35 years [IQR, 24-39 years]). At a median of 11 weeks (IQR, 7-17 weeks) after trauma, serum levels of both ARGS-aggrecan and TNF-α were elevated 1.5-fold (P &lt;.001) compared with reference samples and showed a time-dependent decrease during follow-up. Urine NTX-I and CTX-II concentrations were elevated in an early phase after trauma (1.3-fold [P &lt;.001] and 3.7-fold [P &lt;.001], respectively) compared with reference samples, and CTX-II levels remained elevated compared with reference samples at 2-year follow-up. Strong correlations were found between serum ARGS-aggrecan, urinary NTX-I, and urinary CTX-II (r<sub>s</sub> = 0.57-0.68). Conclusion: In the first few months after an ACL injury, there was a measurable increase in serum levels of ARGS-aggrecan and TNF-α as well as urine levels of NTX-I and CTX-II. These markers remained high compared with those of controls with healthy knees at 2-year follow-up.</p>}},
  author       = {{Hagemans, Frans J.A. and Larsson, Staffan and Reijman, Max and Frobell, Richard B. and Struglics, Andre and Meuffels, Duncan E.}},
  issn         = {{0363-5465}},
  keywords     = {{ACL injury; aggrecan; biomarkers; CTX-II; NTX-I; TNF-α}},
  language     = {{eng}},
  number       = {{13}},
  pages        = {{3534--3543}},
  publisher    = {{SAGE Publications}},
  series       = {{American Journal of Sports Medicine}},
  title        = {{An Anterior Cruciate Ligament Rupture Increases Levels of Urine N-terminal Cross-linked Telopeptide of Type I Collagen, Urine C-terminal Cross-linked Telopeptide of Type II Collagen, Serum Aggrecan ARGS Neoepitope, and Serum Tumor Necrosis Factor–α}},
  url          = {{http://dx.doi.org/10.1177/03635465211042310}},
  doi          = {{10.1177/03635465211042310}},
  volume       = {{49}},
  year         = {{2021}},
}