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Objective: Rupture of the anterior cruciate ligament (ACL) increases the risk of developing osteoarthritis (OA). Delayed Gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) investigates cartilage integrity through T1-analysis after intravenous contrast injection. A high dGEMRIC index represents good cartilage quality. The main purpose of this prospective cohort study was to investigate the prognostic value of the dGEMRIC index regarding future knee OA., Method: 31 patients with ACL injury (mean age 27 ± 6.7 (±SD) years, 19 males) were examined after 2 years with 1.5T dGEMRIC of femoral cartilage. Re-examination 14 years post-injury included weight-bearing knee radiographs, Lysholm and Knee Osteoarthritis Outcome Score (KOOS)., Results: At the 14-year follow up radiographic OA (ROA) was present in 68% and OA symptoms (SOA) in 42% of the injured knees. The dGEMRIC index of the medial compartment was lower in knees that developed medial ROA, 325 ± 68 (ms±SD) vs 376 ± 47 (51 (7-94)) (difference of means (95% confidence interval (CI))), in patients that developed symptomatic OA (SOA), 327 ± 61 vs 399 ± 42 (52 (11-93)), and poor knee function 337 ± 54 vs 381 ± 52 (48 (7-89)) compared to those that did not develop ROA, SOA or poor function. The dGEMRIC index correlated negatively with the OARSI osteophyte score in medial (r = -0.44, P = 0.01) and lateral (r = -0.38, P = 0.03) compartments., Conclusion: The associations between a low dGEMRIC index and future ROA, as well as SOA, are in agreement with previous studies and indicate that dGEMRIC has a prognostic value for future knee OA., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the longitudinal patterns of release, and investigate the association between a set of synovial fluid biomarkers at the acute and chronic stage and the development of radiographic knee osteoarthritis (OA) after an anterior cruciate ligament (ACL) injury., Design: Synovial fluid was aspirated from the acutely ACL-injured knee within the first 2weeks (acute samples), and yearly (chronic samples) up to 7.5 years after injury in 88 subjects (60% men). Non-injured subjects (n = 12) were used as reference group. Aggrecan, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 in synovial fluid were quantified by immunoassays. The presence of radiographic tibiofemoral (TF) or patellofemoral (PF) OA [Kellgren and Lawrence (K&L) ≥2] was examined with weight-bearing knee radiography 16 years after the ACL injury., Results: The average acute and chronic SF concentrations of COMP and aggrecan were elevated in comparison with the reference group (P < 0.001). The levels of COMP and aggrecan clearly decreased approximately half a year after the ACL injury, and returned to reference values during the 7.5 years of follow-up. Using logistic regression analysis neither acute nor chronic concentrations of the four biomarkers were associated with the development of radiographic knee OA at the 16 year follow-up., Conclusion: Increased synovial fluid concentrations of aggrecan and COMP was related to knee injury, but acute and chronic synovial fluid concentrations of aggrecan, COMP, MMP-3 and TIMP-1 failed to predict knee OA 16 years after ACL injury., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess knee cartilage quality and subjective knee function, 20 years after injury in anterior cruciate ligament (ACL) injured copers., Method: We examined 32 knees using delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC), 20 years after a complete ACL tear. Only subjects who had coped with the ACL injury without ACL reconstruction (ACLR), and who presented without radiographic signs of osteoarthritis (OA) at an earlier 16-year follow-up, were included in this study. The quality of the central weight-bearing parts of the medial and lateral femoral cartilage was estimated with dGEMRIC (T1Gd). These results were compared with corresponding results in 24 healthy individuals, and with the subjects' self-reported subjective knee function using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire., Results: The values of T1Gd in the medial and lateral femoral cartilage of the study group (mean (95% CI)), were 404 (385-423) and 427 (399-455) ms, not statistically different from those of the healthy reference group (P = 0.065 and 0.31). The subjective knee function 20 years after the injury, according to the five domains of the KOOS score, was good, with a mean score of 90 ± 11. Values of T1Gd for the medial femoral cartilage were correlated with the KOOS subgroup QOL (P = 0.021, Pearson correlation)., Conclusions: Subjects who have managed to cope with their ACL injury for 20 years with sustained good subjective knee function also seem to have knee cartilage of good quality, with T1Gd values not very different from a healthy reference group., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

There is limited knowledge of knee laxity in the long term after a complete anterior cruciate ligament (ACL) tear treated without ACL reconstruction. The aim of this study was (1) to describe the clinical course of knee laxity after a complete ACL tear over 15 years, and (2) to study the association between knee laxity and meniscal injuries and the development of knee osteoarthritis (OA). We studied 100 consecutive subjects [mean (SD) age 26 (8) years] presenting with acute ACL injury prospectively. The initial treatment in all subjects was knee rehabilitation without reconstructive surgery. The subjects were examined with Lachman's and pivot-shift tests at baseline, 6 weeks, 3 months, 1 year, 3 years and 15 years after the injury. Sagittal knee laxity was also evaluated with the KT-1000 arthrometer at the 15-year follow-up. During follow-up, 22 subjects were ACL reconstructed due to unacceptable knee instability. There was only a mild remaining knee laxity [median Lachman grade and pivot-shift test value of 1 on a 4-grade scale (0-3)] after 15 years in subjects treated without primary ACL reconstruction. Knees with higher anterior sagittal knee laxity 3 months after the injury had a worse long-term outcome with respect to meniscal injuries and knee OA development., (© 2010 John Wiley & Sons A/S.)

Purpose: To evaluate the repeatability of the dGEMRIC (delayed gadolinium enhanced MRI of cartilage) method in osteoarthritis-prone knee joints for three different T1 quantification techniques: two-dimensional inversion recovery (2D-IR), three-dimensional Look-Locker (3D-LL), and three-dimensional variable flip angle (3D-VFA)., Materials and Methods: Nine subjects were examined twice, with a 2-week interval, using all three measurement techniques. Four regions of interest were defined in the central medial and lateral femoral cartilage. The repeatability was evaluated for each measurement technique. For the 3D techniques, the variation between different slices was also evaluated., Results: Repeatability expressed by root-mean-square coefficient of variation (CV(RMS)) showed similar results for 2D-IR and 3D-LL (5.4-8.4%). For 3D-VFA CV(RMS) was higher (9.3-15.2%). Intraclass correlation coefficient showed both 2D-IR and 3D-LL reliability to be moderate, while 3D-VFA reliability was low. Inter-slice CV(RMS) and ICC was of the same magnitude as the repeatability. No clear differences could be interpreted between the condyles., Conclusion: Both 2D-IR and 3D-LL perform well in generating repeatable dGEMRIC results, while 3D-VFA results are somewhat inferior. Furthermore, repeatability results in this study are similar to previously published results for healthy subjects. Finally, the positioning of the analyzed images is crucial to generate reliable repeatability results., (Copyright 2010 Wiley-Liss, Inc.)

Purpose: To present an evaluation method for three-dimensional Look-Locker (3D-LL) based T1 quantification, calculating correct T1 values independent of local flip angle (FA) variations. The method was evaluated both in phantoms and in vivo in a delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) study with 33 subjects., Materials and Methods: T1 was measured with 3D-LL, using both local FA correction and a precalculated FA slice profile, and compared with standard constant FA correction, for all slices in phantoms and in both femur condyles in vivo. T1 measured using two-dimensional Inversion Recovery (2D-IR) was used as gold standard., Results: Due to the FA being slice dependent, the standard constant FA correction results in erroneous T1 (systematic error = 109.1 ms in vivo), especially in the outer slices. With local FA correction, the calculated T1 is excellent for all slices in phantoms (<5% deviation from 2D-IR). In vivo the performance is lower (systematic error = -57.5 ms), probably due to imperfect inversion. With precalculated FA correction the performance is very good also in vivo (systematic error = 13.3 ms)., Conclusion: With the precalculated FA correction method, the 3D-LL sequence is robust enough for in vivo dGEMRIC, even outside the centermost slices., ((c) 2009 Wiley-Liss, Inc.)

Objective: Prevalence and clinical relevance of patellofemoral (PF) osteoarthritis (OA) after anterior cruciate ligament (ACL) injury., Method: Prospectively we studied 94 out of 100 consecutive patients 15 years after acute ACL injury. ACL reconstructions were only performed late if recurrent "give way" persisted or a secondary meniscal injury suitable for repair occurred. The subjects, mean age 42 years, had knee radiographs including skyline PF view taken, which were graded according to the atlas of the Osteoarthritis Research Society International. Knee-related symptoms and function were assessed by questionnaires., Results: PF OA was present in 12/75 knees (16%). Of 94 patients 22 (23%) have had their ACL reconstructed during follow-up. Meniscal injury and ACL reconstruction had occurred more often in knees with PF OA than in knees without PF OA (P=0.004 and P=0.002, respectively). Seven of 15 ACL reconstructed knees showed radiographic PF OA at follow-up. Knees with PF OA had more extension and flexion deficit than knees without PF OA. Subjects with PF OA maintained a higher activity level from injury to follow-up, but did not differ significantly from those without PF OA regarding patient-relevant symptoms and knee function. However, there was a trend for worse outcome in subjects with PF OA., Conclusion: We found a relatively low prevalence of mild PF OA after ACL injury treated non-operatively, and it had limited impact on knee symptoms and patient-relevant knee function. At follow-up PF OA was associated with higher activity level, meniscal injury, extension and flexion deficit, and ACL reconstruction.

Background: The activity level and subjective knee function after an anterior cruciate ligament (ACL) injury treated without reconstruction have not been well elucidated., Hypothesis: Patients with ACL injury can achieve good knee function and satisfactory long-term activity level when treated by early activity modification combined with rehabilitation., Study Design: Cohort study (prognosis); Level of evidence, 2., Materials and Methods: One hundred patients with an acute total ACL injury were observed for 15 years. All patients initially underwent arthroscopic surgery and a rehabilitation program. They were advised to modify their activity level, especially by avoiding contact sports. Patients with recurrent giving-way episodes and/or secondary meniscal injuries that required fixation (n = 6) were subsequently excluded and underwent reconstruction (n = 22). Sixty-seven patients with unilateral nonreconstructed ACL injury remained at the 15-year follow-up. The Lysholm knee score, Tegner activity level, and a visual analog score for global knee function were recorded at regular intervals. At the final follow-up, patients were further evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective knee evaluation form., Results: Forty patients resumed their preinjury activity level or higher within 3 years. The median activity level 15 years after injury had decreased from 7 to 4 according to Tegner activity scale (P < .001). The mean Lysholm knee score was 96 and 95, 1 and 3 years after injury, respectively, but declined to 86 after 15 years (P < .001). Forty-nine patients had good/excellent results, and 14 had fair (n = 6) or poor function (n = 8) at 15 years. Patients injured in contact sports scored lower in the quality of life sub-scale of KOOS than those injured in noncontact sports (P < .05). Thirteen of the 67 patients (19%) were reoperated with an arthroscopic procedure because of knee symptoms., Conclusion: Early activity modification and neuromuscular rehabilitation resulted in a good knee function and an acceptable activity level in the majority of the nonreconstructed patients. The decline in activity level of patients engaged in contact sports at the time of injury affected their subjective quality of life more than patients involved in noncontact sports.

Objective: To examine the glycosaminoglycan (GAG) content in cartilage and that in synovial fluid and determine whether they are associated, in patients with an acute anterior cruciate ligament (ACL) injury., Methods: Twenty-four patients (14 of whom were male) with a mean age of 27 years (range 17-40 years) were assessed with delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage an average of 3 weeks after an ACL rupture and compared with 24 healthy volunteers. Two hours after an intravenous injection of Gd-DTPA(2-) (0.3 mmoles/kg body weight), quantitative measurements of the T1 relaxation time (T1(Gd) [T1 relaxation time in the presence of Gd-DTPA]) were made in lateral and medial femoral weight-bearing cartilage. In the patients, synovial fluid was aspirated immediately before the MRI, and GAG was analyzed using dye precipitation with Alcian blue., Results: Fifteen of the 24 patients had an isolated bone bruise in the lateral femoral condyle, where the cartilage T1(Gd) was shorter than that in the controls (mean +/- SD 385 +/- 83 msec and 445 +/- 41 msec, respectively; P = 0.004), consistent with decreased GAG content. However, the T1(Gd) was also decreased in the medial femoral cartilage, where bone bruises were rare (376 +/- 76 msec in patients versus 428 +/- 38 msec in controls; P = 0.006). The mean +/- SD synovial fluid GAG concentration in patients was 157 +/- 86 mug/ml and showed a positive correlation with the T1(Gd) (r = 0.49, P = 0.02)., Conclusion: This study indicates that an ACL injury causes posttraumatic edema of the lateral femoral cartilage but initializes a generalized biochemical change within the knee that leads to GAG loss from both lateral and medial femoral cartilage. In cartilage with a high GAG content (long T1(Gd)), more GAG is released into the synovial fluid, suggesting that cartilage quality is a factor to consider when interpreting cartilage biomarkers of metabolism.

The degree of cartilage changes by arthroscopic and radiologic examination was evaluated in a retrospective, cross-sectional study of 1012 patients with knee complaints at different times after knee injury. Patients were classified by age, sex, trauma date and type of injury. The condition of the cartilage was graded on a 1-10 scale based on findings at arthroscopy and on weight-bearing radiographs. Patients with injury to the anterior cruciate ligament (isolated or combined with injury to meniscus or collateral ligaments) showed the first radiologic signs (joint space narrowing) of osteoarthritis (OA) at an average age of about 40 years, while patients with isolated meniscus injury had the same stage of disease at an average age of about 50 years. Both study groups displayed the first radiologic signs of OA on average about 10 years after the injury and showed increasingly serious arthroscopic and radiologic signs of joint damage with increased time between injury and examination. For patients who sustained an isolated meniscus injury between the ages of 17 and 30, the average time until development of radiologic signs of OA was about 15 years, while for those who had the same injury over the age of 30, the corresponding time interval was only about 5 years. We conclude from this that knee OA becomes increasingly severe with increased time between joint injury and examination. OA changes appear sooner in older patients with knee injury than in the young.

This is the first study which quantifies aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinases-1 (TIMP-1) in SF samples prospectively obtained from the same patient at different time intervals after a cruciate ligament injury of the knee. Aggrecan fragment concentrations were determined by dye precipitation with Alcian Blue. Stromelysin-1 and TIMP-1 were analysed by immunoassay. Ten healthy volunteers formed the reference group. Immediately after knee injury, all marker concentrations were higher as compared to the reference group. The high marker concentrations decreased gradually with time, and in samples obtained between 6 months and 6 years after the injury, median concentrations of some of the markers were not different compared to reference levels. This was in contrast to results from previous cross-sectional studies, where chronic phase median concentrations of all markers were consistently higher than reference levels. In previous cross-sectional studies, however, the samples were obtained at arthroscopy done because of knee complaints at different times after a knee injury. In the present study, the knee injured patients visited the orthopaedic outpatient ward only for SF sampling, and they had no or only minor knee symptoms. We conclude that the temporal changes of marker concentrations in joint fluid after knee injury, suggested from cross-sectional studies, have now been confirmed in a longitudinal, prospective cohort study. We further find that in patients with mild knee symptoms in the chronic phase after cruciate ligament injury, median SF levels of aggrecan fragments, stromelysin-1, and TIMP-1 are lower than in patients with significant knee complaints after the same type of injury.(ABSTRACT TRUNCATED AT 250 WORDS)