Infrapatellar fat pad abnormalities are associated with a higher inflammatory synovial fluid cytokine profile in young adults following ACL tear

To evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1ρ and T2 relaxation time me...

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Published in:	Osteoarthritis and cartilage Vol. 28; no. 1; pp. 82 - 91
Main Authors:	Heilmeier, U., Mamoto, K., Amano, K., Eck, B., Tanaka, M., Bullen, J.A., Schwaiger, B.J., Huebner, J.L., Stabler, T.V., Kraus, V.B., Ma, C.B., Link, T.M., Li, X.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-01-2020
Subjects:	Adipose Tissue - diagnostic imaging Adipose Tissue - pathology Adult Anterior Cruciate Ligament Injuries - metabolism Anterior Cruciate Ligament Injuries - pathology Anterior Cruciate Ligament Reconstruction Anterior cruciate ligament tear Cartilage damage Cytokines - analysis Cytokines - metabolism Female Humans Inflammation Knee - diagnostic imaging Knee - pathology Magnetic Resonance Imaging Male Matrix metalloproteinases Post-traumatic osteoarthritis (PTOA) Synovial Fluid - chemistry Synovial Fluid - metabolism Synovitis - diagnostic imaging Synovitis - metabolism Synovitis - pathology T1ρ relaxation time T2 relaxation time T1ρ relaxation time Matrix metalloproteinases Magnetic resonance imaging Anterior cruciate ligament tear Post-traumatic osteoarthritis (PTOA) Cartilage damage Inflammation T2 relaxation time
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Summary:	To evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1ρ and T2 relaxation time measurements. 26 patients with acute ACL tears underwent 3T MR scanning of the injured knee prior to ACL reconstruction. The presence and degree of abnormalities of the infrapatellar (IPFP) and the suprapatellar (SPFP) fat pads were scored on MR images along with grading of effusion-synovitis and synovial proliferations. Knee cartilage composition was assessed by 3T MR T1ρ and T2 mapping in six knee compartments. We quantified concentrations of 20 biomarkers in synovial fluid aspirated at the time of ACL reconstruction. Spearman rank partial correlations with adjustments for age and gender were employed to evaluate correlations of MR, particularly cartilage composition and fat pad abnormalities, and biomarker data. The degree of IPFP abnormality correlated positively with the synovial levels of the inflammatory cytokine markers IFN-γ (ρpartial = 0.64, 95% CI (0.26–0.85)), IL-10 (ρpartial = 0.47, 95% CI (0.04–0.75)), IL-6 (ρpartial = 0.56, 95% CI (0.16–0.81)), IL-8 (ρpartial = 0.49, 95% CI (0.06–0.76)), TNF-α (ρpartial = 0.55, 95% CI (0.14–0.80)) and of the chondrodestructive markers MMP-1 and -3 (MMP-1: ρpartial = 0.57, 95% CI (0.17–0.81); MMP-3: ρpartial = 0.60, 95% CI (0.21–0.83)). IPFP abnormalities were significantly associated with higher T1ρ and T2 values in the trochlear cartilage (T1ρ: ρpartial = 0.55, 95% CI (0.15–0.80); T2: ρpartial = 0.58, 95% CI (0.18–0.81)) and with higher T2 values in the medial femoral, medial tibial as well as in patellar cartilage (0.45 ≤ ρpartial ≤ 0.59). Correlations between SPFP abnormalities and synovial markers were not significant except for IL-6 (ρpartial = 0.57, 95% CI (0.17–0.81)). This exploratory study suggests that acute ACL rupture can be associated with damage to knee tissues such as the inferior fat pad of the knee. Such fat pad injury could be partially responsible for the apparent post-injury pro-inflammatory response noted in ACL-injured individuals. However, future longitudinal studies are needed to link ACL-rupture associated fat pad injury with important patient outcomes such as the development of posttraumatic osteoarthritis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author’s contributions UH is the primary author and contributed to the manuscript in the following ways: conception and design, acquisition of fat pad scoring data and compiling of clinical data, analysis and interpretation of data, statistical modeling, manuscript drafting and revision. UH and KM contributed equally. KM contributed to the manuscript in the conception and design, analysis and interpretation of data, statistical modeling, manuscript drafting and revision. The following authors contributed as described: KA (acquisition and analysis of biomarker data and clinical data, statistical analysis, interpretation of data, and revision), MT (collection of data, cartilage segmentation, and manuscript revision), BS (conception and acquisition of fat pad scoring data, manuscript revision), JB and BE (statistical design, reanalysis and interpretation of data, manuscript revision), JL, TS and VK (acquisition and interpretation of fluid biomarker data, manuscript revision), BM (acquisition of clinical data and joint fluid, data interpretation and manuscript revision), TML (conception and acquisition of fat pad scoring data, manuscript revision), XL (study supervisor, conception and design, data analysis and interpretation, manuscript revision). KM and XL take responsibility for the integrity of the data. All authors gave their final approval of the manuscript version that has been submitted. Co-first author with equal contributions
ISSN:	1063-4584 1522-9653
DOI:	10.1016/j.joca.2019.09.001