Molecular and Structural Biomarkers of Inflammation at Two Years After Acute Anterior Cruciate Ligament Injury Do Not Predict Structural Knee Osteoarthritis at Five Years

Roemer, Frank W.; Englund, Martin; Turkiewicz, Aleksandra; Struglics, A.; Guermazi, Ali; Lohmander, L. Stefan; Larsson, S.; Frobell, Richard

doi:10.1002/art.40687

Cited by 30 publications

(47 citation statements)

References 16 publications

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“…In Sweden, approximately 80/100,000 people per year experience anterior cruciate ligament (ACL) rupture; in the U.S. there are 252,000 ACL injuries per year1, 2. 50% of people with significant knee joint injuries such as ACL rupture and/or acute meniscal tear subsequently develop symptomatic radiographic OA within 10 years, so-called post-traumatic OA (PTOA) 3 ; at least 33% with acute ACL rupture will have magnetic resonance imaging (MRI)-defined whole joint OA after 5 years 4 . PTOA is thought to comprise around 12% of all OA, although its incidence appears to be increasing5, 6.…”

Section: Introductionmentioning

confidence: 99%

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

Watt

Corp

Kingsbury

et al. 2019

Osteoarthritis and Cartilage

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Section: Introductionmentioning

confidence: 99%

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

Watt

Corp

Kingsbury

et al. 2019

Osteoarthritis and Cartilage

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“…Studies of associations between molecular biomarkers and MRI cartilage ndings have been called for (32). Only a couple of studies on association between synovial uid molecular biomarkers and MRI cartilage ndings 3 to 5 years after an ACL injury have been published (33,34), and studies with longer follow-up time are lacking.…”

Section: Introductionmentioning

confidence: 99%

Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later

Neuman¹,

Larsson²,

Lohmander³

et al. 2020

Preprint

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Background. To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury.Methods. We studied 25 patients with a complete ACL rupture without subsequent ACL reconstruction or radiographic knee OA. All had a delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) 20 years after the ACL injury, using the T1 transverse relaxation time in the presence of gadolinium (T1Gd) which estimates the concentration of glycosaminoglycans in hyaline cartilage. Synovial fluid samples were aspirated acutely (between 0 and 18 days) and during 1 to 5 follow up visits between 0.5 and 7.5 years after injury. We quantified synovial fluid concentrations of aggrecan (epitopes 1-F21 and ARGS), cartilage oligomeric matrix protein, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by immunoassays, and sulfated glycosaminoglycans by Alcian blue precipitation. Western blot was used for qualitative analyses of aggrecan fragments in synovial fluid and cartilage samples.Results. Western blot indicated that the 1-F21 epitope was located within the chondroitin sulfate 2 region of aggrecan. Linear regression analyses (adjusted for age, sex, body mass index and time between injury and sampling) showed that acute higher synovial fluid 1-F21-aggrecan concentrations were associated with shorter T1Gd values 20 years after injury, i.e. inferior cartilage quality (standardized effects between -0.67 and -1.0). No other statistically significant association was found between molecular biomarkers and T1Gd values. Conclusion. Higher acute synovial fluid 1-F21-aggrecan concentrations in ACL injured patients, who managed to cope without ACL reconstruction and were without radiographic knee OA, were associated with inferior knee cartilage quality assessed by dGEMRIC 20 years after injury.

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“…Studies of associations between molecular biomarkers and MRI cartilage findings have been called for [32]. Only a couple of studies on association between synovial fluid molecular biomarkers and MRI cartilage findings 3 to 5 years after an ACL injury have been published [33,34], and studies with longer follow-up time are lacking.…”

Section: Introductionmentioning

confidence: 99%

Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later

Neuman

Larsson

Lohmander

et al. 2020

BMC Musculoskelet Disord

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Background To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury. Methods We studied 25 patients with a complete ACL rupture without subsequent ACL reconstruction or radiographic knee OA. All had a delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) 20 years after the ACL injury, using the T1 transverse relaxation time in the presence of gadolinium (T1Gd) which estimates the concentration of glycosaminoglycans in hyaline cartilage. Synovial fluid samples were aspirated acutely (between 0 and 18 days) and during 1 to 5 follow up visits between 0.5 and 7.5 years after injury. We quantified synovial fluid concentrations of aggrecan (epitopes 1-F21 and ARGS), cartilage oligomeric matrix protein, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by immunoassays, and sulfated glycosaminoglycans by Alcian blue precipitation. Western blot was used for qualitative analyses of aggrecan fragments in synovial fluid and cartilage samples. Results Western blot indicated that the 1-F21 epitope was located within the chondroitin sulfate 2 region of aggrecan. Linear regression analyses (adjusted for age, sex, body mass index and time between injury and sampling) showed that acute higher synovial fluid 1-F21-aggrecan concentrations were associated with shorter T1Gd values 20 years after injury, i.e. inferior cartilage quality (standardized effects between − 0.67 and − 1.0). No other statistically significant association was found between molecular biomarkers and T1Gd values. Conclusion Higher acute synovial fluid 1-F21-aggrecan concentrations in ACL injured patients, who managed to cope without ACL reconstruction and were without radiographic knee OA, were associated with inferior knee cartilage quality assessed by dGEMRIC 20 years after injury.

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Molecular and Structural Biomarkers of Inflammation at Two Years After Acute Anterior Cruciate Ligament Injury Do Not Predict Structural Knee Osteoarthritis at Five Years

Abstract: Neither MRI-detected inflammation nor selected SF/serum inflammation biomarkers at 2 years postinjury predicted ROA or MROA at 5 years postinjury. Concordance between MRI and SF inflammatory biomarkers was weak.

Cited by 30 publications

References 16 publications

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later

Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later

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