Quantitative evaluation of the tibiofemoral joint cartilage by T2 mapping in patients with acute anterior cruciate ligament injury vs contralateral knees: results from the subacute phase using data from the NACOX study cohort.

OBJECTIVE: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. DESIGN: Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. RESULTS: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. CONCLUSION: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. TRIAL REGISTRATION NUMBER: NCT02931084.

Early anterior cruciate ligament reconstruction does not affect 5 year change in knee cartilage thickness: secondary analysis of a randomized clinical trial.

OBJECTIVE: To compare 5-year change in femorotibial cartilage thickness in 121 young, active adults with an acute anterior cruciate ligament (ACL) tear randomized to a strategy of structured rehabilitation plus early ACL reconstruction (ACLR) or structured rehabilitation plus optional delayed ACLR. DESIGN: 62 patients were randomized to early ACLR, 59 to optional delayed ACLR. Magnetic resonance imaging (MRI) was acquired within 4 weeks of injury, at two- and 5-years follow-up. Main outcome was 5-year change in overall femorotibial cartilage thickness. Secondary outcomes included the location-independent cartilage ChangeScore, summarizing thinning and thickening in 16 femorotibial subregions. An exploratory as-treated comparison was performed additionally. RESULTS: Baseline and at least one follow-up MRI were available for 117 patients. Over 5 years, a comparable increase in overall femorotibial cartilage thickness was observed for patients randomized to early ACLR (n = 59) and patients randomized to optional delayed ACLR (n = 58, adjusted mean difference: -5 µm, 95% CI: [-118, 108]µm). However, the location-independent cartilage ChangeScore was greater in those treated with early ACLR than in patients treated with optional delayed ACLR (adjusted mean difference: 403 µm [119, 687]µm). As-treated analysis showed no between-group differences for the main outcome, while the location-independent cartilage ChangeScore was greater for patients treated with early (adjusted mean difference: 632 µm [268, 996]µm) or delayed ACLR (adjusted mean difference: 449 µm [108, 791]µm) than for patients treated with rehabilitation alone. CONCLUSIONS: In young active adults with acute ACL-injury, choice of treatment strategy for the injured ACL did not modify the magnitude of 5-year change in overall femorotibial cartilage thickness. TRIAL REGISTRATION: ISRCTN84752559.

Is meniscal status in the anterior cruciate ligament injured knee associated with change in bone surface area? An exploratory analysis of the KANON trial.

OBJECTIVES: To study bone shape changes as a potential early feature of post-traumatic structural knee OA development, we estimated the association between meniscal status in the anterior cruciate ligament (ACL) injured knee and longitudinal condyle changes in bone surface area. DESIGN: We used data from the KANON trial, including 121 young ACL-injured adults. We obtained baseline and 2-year follow-up knee MRIs. Our outcome was change in the bone surface areas (mean mm2, log-transformed) in 4 locations (femur, tibia, patella, and trochlea femur) in the medial and lateral compartment from baseline to 2 years. Meniscal pathology was defined as both present at baseline and newly developed (i.e., incident or progressed) using ACLOAS. We used multilevel linear regression adjusted for baseline bone area, age, sex, body mass index, treatment arm (i.e., early or optional delayed ACL reconstruction), and location. We analyzed medial and lateral compartment separately. We present results as percentage (%) bone area change difference with 95% confidence intervals (CI). RESULTS: We analyzed 109 subjects (median 27 (18-36) years, 83% men) due to missing MRI information. The bone surface area increased on average by ∼2% over 2 years. The differences between knees with and without baseline meniscal pathology were 1.1% (95%CI 0.0-2.3%) and 1.4% (95%CI 0.6-2.2%) in the medial and lateral compartment, respectively, and 1.2% (95%CI 0.3-2.0%) and 1.3% (95%CI 0.6-2.0%) for medial and lateral newly developed pathology, respectively. CONCLUSION: Our finding of ∼1% increase bone area in compartment with meniscal pathology suggests a potentially important association between meniscal integrity and early bone surface area changes after ACL injury. Trial registration number ISRCTN 84752559.

Molecular and imaging biomarkers of local inflammation at 2 years after anterior cruciate ligament injury do not associate with patient reported outcomes at 5 years.

OBJECTIVE: To estimate the association between molecular or imaging inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury and patient-reported outcomes at 5 years. METHODS: For 116 ACL-injured patients, molecular biomarkers of inflammation (synovial fluid and serum cytokines) and Hoffa- and effusion-synovitis as visualized on magnetic resonance imaging (MRI) were assessed 2 years post-injury. Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were assessed at 2 and 5 years. We used multiple imputation to handle biomarker values that were below the level of detection or missing, and linear regression for statistical analyses. RESULTS: None of the synovial fluid cytokines or imaging biomarkers of inflammation at 2 years were associated with any of the patient-reported outcomes at 5 years. With each log10 unit higher of serum tumor necrosis factor concentration the knee-related quality of life of KOOS was increased (i.e., better outcome) by 35 (95% confidence interval 7 to 63) points. No other serum biomarker measured at 2 years was associated with patient-reported outcome at 5 years. CONCLUSION: Local joint inflammation assessed by biomarkers in synovial fluid and Hoffa- and effusion-synovitis on MRI at 2 years after an ACL injury did not associate with patient-reported outcomes at 5 years. Thus, chronic inflammation in the ACL-injured knee, as reflected by the biomarkers studied here, seems not to be a key determinant for the long-term patient-reported outcomes.

Marked and rapid change of bone shape in acutely ACL injured knees - an exploratory analysis of the Kanon trial.

BACKGROUND: To investigate changes in knee 3D bone shape over the first 5 years after acute anterior cruciate ligament (ACL) injury in participants of the randomized controlled KANON-trial. METHODS: Serial MR images over 5 years from 121 young (32 women, mean age 26.1 years) adults with an acute ACL tear in a previously un-injured knee were analyzed using statistical shape models for bone. A matched reference cohort of 176 individuals was selected from the Osteoarthritis Initiative (OAI). Primary endpoint was change in bone area of the medial femoral condyle; exploratory analyses compared results by treatment and examined other knee regions. Comparisons were made using repeated measures mixed model ANOVA with adjustment for age, sex and body mass index (BMI). RESULTS: Mean medial femur bone area increased 3.2% (78.0 [95% CI 70.2 to 86.4] mm2) over 5 years after ACL injury and most prominently in knees treated with ACL reconstruction (ACLR). A higher rate of increase occurred over the first 2 years compared to the latter 3-years (66.2 [59.3 to 73.2] vs 17.6 [12.2 to 23.0] mm2) and was 6.7 times faster than in the reference cohort. The pattern and location of shape change in the extrapolated KANON data was very similar to that observed in another knee-osteoarthritis cohort. CONCLUSION: 3D shape modelling after acute ACL injury revealed rapid bone shape changes, already evident at 3 months. The bone-change pattern after ACL injury demonstrated flattening and bone growth on the outer margins of the condyles similar to that reported in established knee osteoarthritis.

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.

OBJECTIVE: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. DESIGN: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. RESULTS: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. CONCLUSIONS: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.

Changes in synovial fluid and serum concentrations of cartilage oligomeric matrix protein over 5 years after anterior cruciate ligament rupture: an exploratory analysis in the KANON trial.

OBJECTIVE: To monitor longitudinal changes of cartilage oligomeric matrix protein (COMP) in synovial fluid (sf) and serum (s) over 5 years after acute anterior cruciate ligament (ACL) rupture, and to compare results from two commercial COMP immunoassays. DESIGN: Bio-fluids were collected from 121 patients on six occasions over 5 years after acute ACL injury, and from 25 knee healthy reference subjects. Concentrations of sf- and sCOMP were measured by AnaMar (sCOMP-Ana) and by BioVendor (sf- and sCOMP-Bio) immunoassays; other biomarkers were previously assessed. We used ANCOVA for group comparisons and linear mixed models for associations between biomarkers over 5-years with P < 0.05 considered a statistically significant difference or association. RESULTS: Compared to the reference group, sfCOMP-Bio concentrations were 2-fold elevated within 6 weeks after ACL injury and remained elevated 5 years thereafter, whereas sCOMP-Bio and sCOMP-Ana concentrations were no different from reference levels at any time point. Over the 5-year period, there was an association between sCOMP-Bio and sCOMP-Ana concentrations, although neither sCOMP-Bio nor sCOMP-Ana associated with sfCOMP-Bio. sfCOMP-Bio associated with SF ARGS-aggrecan, urine type I and II collagens (uNTX-I and uCTX-II) and SF cytokines, while sCOMP-Bio associated inversely with uCTX-II, uNTX-I and SF cytokines. CONCLUSION: The local process after an acute ACL injury generates increased SF COMP concentrations in the injured knee up to 5 years after injury. This response is not detected in serum. Discrepancies in associations between sCOMP measured by BioVendor and AnaMar immunoassays with other biomarkers indicate differences in detected COMP fragments.

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial.

OBJECTIVE: Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years. DESIGN: We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA). RESULTS: Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated. CONCLUSIONS: Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines.

Epidemiology of intra- and peri-articular structural injuries in traumatic knee joint hemarthrosis - data from 1145 consecutive knees with subacute MRI.

OBJECTIVE: In patients with traumatic knee distorsion and hemarthrosis, to investigate the panorama of structural injury, as visualized on magnetic resonance imaging (MRI). DESIGN: Cohort study of 1145 consecutive patients with traumatic knee distorsion who underwent MRI within median 8 days after injury. We present structural injury as visualized on MRI in relation to age, sex and activity at injury. Population based gender specific annual incidences of common structural injuries were calculated. RESULTS: The majority of injuries (72%) occurred during sports. Overall, anterior cruciate ligament (ACL) rupture was the most common structural injury (52%), followed by meniscal tear (41%) and lateral patella dislocation (LPD, 17%). Only 12% of ACL tears were isolated with meniscal tear being the most common associated injury (55%). The annual incidence of ACL injury was 77 (70-85, 95% CI) per 100,000 inhabitants with significant differences between men (91, 80-103) and women (63, 53-73). In those aged 16 years and younger, LPD was the most frequent structural injury, both in boys (39%) and girls (43%). In this age group, the annual incidence of LPD was 88 (68-113) and higher in boys (113, 81-154) than in girls (62, 39-95). CONCLUSIONS: ACL injury occurs in one out of two knees with traumatic hemarthrosis but only 12% are without concomitant structural injury. The overall rate of traumatic knee hemarthrosis and ACL injury is higher in men. In those aged 10-19 years, ACL rupture is more common among girls than boys whereas in those 16 years and younger, LPD is more common among boys than girls.

Risk factors for meniscal body extrusion on MRI in subjects free of radiographic knee osteoarthritis: longitudinal data from the Osteoarthritis Initiative.

OBJECTIVE: To determine risk factors associated with increased meniscal body extrusion on knee magnetic resonance (MR) images in subjects free of radiographic osteoarthritis (OA). METHODS: We selected 340 subjects (aged 45-55 years, mean [SD] body mass index 26.7 [4.4], 51% women) with Kellgren-Lawrence grade 0 in both knees and bilateral knee MR images available at the baseline, 24 months, 48 months, and 72 month exam from the Osteoarthritis Initiative (OAI). We assessed mid-coronal 3-T MR images from baseline through the 72-month exam. One observer measured widths of the tibia plateau and medial or lateral meniscal body extrusion for baseline and 72 months follow-up. Another observer assessed meniscal integrity at all four time points. We calculated an extrusion ratio ([meniscal body extrusion]/[tibia width] × 100) to account for knee size. We evaluated risk factors for increased meniscal body extrusion ratio from baseline to 72 months by a multivariable linear regression mixed model for medial and lateral compartment, respectively. RESULTS: In the medial compartment female sex (ß = 0.35; 95% confidence interval [CI] 0.16-0.53), incident meniscal tear (ß = 0.29; 95% CI 0.22-0.55), and the baseline value of the extrusion ratio (ß = 0.63; 95% CI 0.56-0.70) were associated with increased extrusion ratio by 72 months. Results were similar for the lateral compartment. CONCLUSIONS: Only female sex, incident meniscal tear, and higher baseline value of extrusion are risk factors for increased meniscal body extrusion in subjects free of radiographic OA. The results suggest that meniscal extrusion may contribute to and mediate the well-known increase in knee OA incidence in middle-aged women.

Type II collagen C2C epitope in human synovial fluid and serum after knee injury--associations with molecular and structural markers of injury.

PURPOSE: Investigate in a cross-sectional study time-dependent changes of synovial fluid type II collagen epitope C2C concentrations after knee injury and correlate to other joint injury biomarkers. METHODS: Synovial fluid samples were aspirated between 0 days and 7 years after injury (n = 235). Serum was collected from 71 of the knee injured patients. Synovial fluid from 8 knee-healthy subjects was used as reference. C2C was quantified by immunoassay and structural injury was determined from magnetic resonance images (MRI) of the injured knee acquired 1-38 days after injury (n = 98). Additional joint injury biomarker results were from earlier investigations of the same samples. RESULTS: Synovial fluid C2C concentrations were higher in injured knees than in knees of reference subjects from 1 day up to 7 years after injury. C2C concentrations in synovial fluid and serum were correlated (r = 0.403, P < 0.001). In synovial fluid from subjects early after injury (0-33 days), C2C concentrations were correlated with cross-linked C-telopeptide of type II collagen (r = 0.444, P = 0.003), ARGS-aggrecan (r = 0.337, P < 0.001), osteocalcin (r = 0.345, P < 0.001), osteopontin (r = 0.371, P < 0.001) and IL-8 (r = -0.385, P < 0.001), but not with structural joint injury as visualized on MRI. CONCLUSION: The increased levels of synovial fluid C2C after injury, together with the associations seen with several other injury-related biomarkers, suggest that an acute knee injury is associated with an immediate and sustained local degradation of type II collagen.

Increased risk for radiographic osteoarthritis features in young active athletes: a cross-sectional matched case-control study.

OBJECTIVE: Prevalence data on radiographic osteoarthritis (ROA) in young active athletes is sparse. Aim was to assess in a matched case-control design the frequency of ROA in an athlete population and whether athlete status, gender, previous anterior cruciate ligament (ACL) surgery and age increase the odds for ROA. DESIGN: 135 consecutive athletes (82% soccer players) 18-36 years old and 550 non-athletes aged-matched controls had knee radiography (Lyon-Schuss protocol) for assessment of subacute or chronic knee complaints. Patients with acute trauma or fractures were excluded. Radiographs were graded according to the Kellgren-Lawrence and OARSI grading schemes. In addition, medial and lateral intercondylar notch osteophytes were scored. We used logistic regression model to assess the association of ROA and specific radiographic OA features with athlete status, prior ACL surgery, gender and age, adjusting for each other. RESULTS: 19.4% of patients were 18-22 years old, 26.4% were 23-27, 22.6% were 28-32, and 31.5% were 33-36 years old. 18.7% were female and 8.8% had previous ACL surgery. 8.5% had ROA and 6.0% had evidence of JSN. The adjusted odds ratios (aOR) for ROA were 2.8 (95% confidence interval 1.4, 5.5) for athletes, 7.0 (3.5, 13.9) for previous ACL surgery and 3.3 (1.2, 9.0) for age range 32-36. Athlete status significantly increased odds for tibiofemoral osteophytes [aOR 2.9 (1.6, 5.4)] and comparably for notch osteophytes [aOR 2.3 (1.1, 4.7)]. CONCLUSIONS: Athlete status, higher age and previous ACL surgery increase the risk of ROA with surgery being the strongest risk factor.

Imaging following acute knee trauma.

Joint injury has been recognized as a potent risk factor for the onset of osteoarthritis. The vast majority of studies using imaging technology for longitudinal assessment of patients following joint injury have focused on the injured knee joint, specifically in patients with anterior cruciate ligament injury and meniscus tears where a high risk for rapid onset of post-traumatic osteoarthritis is well known. Although there are many imaging modalities under constant development, magnetic resonance (MR) imaging is the most important instrument for longitudinal monitoring after joint injury. MR imaging is sensitive for detecting early cartilage degeneration and can evaluate other joint structures including the menisci, bone marrow, tendons, and ligaments which can be sources of pain following acute injury. In this review, focusing on imaging following acute knee trauma, several studies were identified with promising short-term results of osseous and soft tissue changes after joint injury. However, studies connecting these promising short-term results to the development of osteoarthritis were limited which is likely due to the long follow-up periods needed to document the radiographic and clinical onset of the disease. Thus, it is recommended that additional high quality longitudinal studies with extended follow-up periods be performed to further investigate the long-term consequences of the early osseous and soft tissue changes identified on MR imaging after acute knee trauma.

The effect of anterior cruciate ligament injury on bone curvature: exploratory analysis in the KANON trial.

OBJECTIVE: Investigate the 5-year longitudinal changes in bone curvature after acute anterior cruciate ligament (ACL) injury, and identify predictors of such changes. METHODS: In the KANON-trial (ISRCTN 84752559), 111/121 young active adults with an acute ACL tear to a previously un-injured knee had serial 1.5 T MR images from baseline (within 5 weeks from injury) to 5 years after injury. Of these, 86 had ACL reconstruction (ACLR) performed early or delayed, 25 were treated with rehabilitation alone. Measures of articulating bone curvature were obtained from computer-assisted segmentation of MR images. Curvature (mm(-1)) was determined for femur, tibia, medial/lateral femur, trochlea, medial/lateral tibia. Age, sex, treatment, BMI, meniscal injury, osteochondral fracture on baseline MR images were tested for association. RESULTS: Over 5 years, curvature decreased in each region (P < 0.001) suggesting flattening of convex shapes and increased concavity of concave shapes. A higher BMI was associated with flattening of the femur (P = 0.03), trochlea (P = 0.007) and increasing concavity of the lateral tibia (LT) (P = 0.011). ACLR, compared to rehabilitation alone, was associated with flatter curvature in the femur (P < 0.001), medial femoral condyle (P = 0.006) and trochlea (P = 0.003). Any meniscal injury at baseline was associated with a more flattened curvature in the femur (P = 0.038), trochlea (P = 0.039), lateral femoral condyle (P = 0.034) and increasing concavity of the LT (P = 0.048). CONCLUSION: ACL injury is associated with significant changes in articulating bone curvature over a 5 year period. Higher BMI, baseline meniscal injury and undergoing ACL reconstruction (as distinct from undergoing rehabilitation alone) are all associated with flattening of the articulating bone.

Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI.

OBJECTIVE: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. METHODS: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 ± 9.6 yrs, BMI 29.4 ± 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. RESULTS: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% CI 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 1.35-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. CONCLUSION: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded.

Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis)--a cross-sectional analysis.

PURPOSE: The aim of this cross-sectional study was to investigate concentrations of cartilage and bone markers, and pro-inflammatory cytokines in synovial fluid (SF) collected at different time-points from acutely injured knees with hemarthrosis and to compare these with SF concentrations of knees of age and gender-matched healthy reference subjects. METHODS: SF was aspirated from the acutely injured knee of 111 individuals (mean age 27 years, span 13-64 years, 22% women). Concentrations of sulfated glycosaminoglycan (sGAG) were measured by Alcian blue precipitation whereas cartilage ARGS, bone biomarkers [osteocalcin (OCL), secreted protein acidic and rich in cysteine (SPARC) and osteopontin (OPN)] and pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor (TNF)-α] were analyzed using electrochemiluminescence. Samples were also analyzed with regard to time between injury and aspiration [same day (n = 29), 1 day (n = 31), 2-3 days (n = 19), 4-7 days (n = 20) and 8-23 days (n = 12)]. RESULTS: SF concentrations of ARGS (P < 0.001), SPARC (P < 0.001), OPN (P < 0.001), and all cytokines (P < 0.001), but not sGAG (P = 0.06) or OCL (P = 0.992), were significantly higher in injured knees compared to knees of reference subjects. The cartilage markers sGAG and ARGS were significantly higher in knees aspirated later than 1 day after injury, whereas concentrations of SPARC and OPN and all cytokines were higher in knees aspirated the same day as the injury and at all time-points thereafter. CONCLUSIONS: Our results suggest that an acute knee injury is associated with an instant local biochemical response to the trauma, which may affect cartilage and bone as well as the inflammatory activity.

Morphometric differences between the medial and lateral meniscus in healthy men - a three-dimensional analysis using magnetic resonance imaging.

The objective of this work was to characterize tibial plateau coverage and morphometric differences of the medial (MM) and lateral meniscus (LM) in a male reference cohort using three-dimensional imaging. Coronal multiplanar reconstructions of a sagittal double-echo steady state with water excitation magnetic resonance sequence (slice thickness: 1.5 mm, and in-plane resolution: 0.37 × 0.70 mm) were analyzed in 47 male participants without symptoms, signs or risk factors of knee osteoarthritis of the reference cohort of the Osteoarthritis Initiative. The medial and lateral tibial (LT) plateau cartilage area and the tibial, femoral and external surfaces of the MM and LM were manually segmented throughout the entire knee. This process was assisted by parallel inspection of a coronal intermediately weighted turbo spin echo sequence. Measures of tibial coverage, meniscus size, and meniscus position were computed three-dimensionally for the total menisci, the body, and the anterior and the posterior horn. The LM was found to cover a significantly greater (p < 0.001) proportion of the LT plateau (59 ± 6.8%) than the MM of the medial plateau (50 ± 5.5%). Whereas the volume of both menisci was similar (2.444 vs. 2.438 ml; p = 0.92), the LM displayed larger tibial and femoral surface areas (p < 0.05) and a smaller maximal (7.2 ± 1.0 vs. 7.7 ± 1.1 mm; p < 0.01) and mean thickness (2.7 ± 0.3 vs. 2.8 ± 0.3 mm; p < 0.001) than the medial one. Also, the LM displayed less (physiological) extrusion than the medial one. These data may guide strategies for meniscal tissue engineering and transplantation aiming to restore normal joint conditions.

Presence, location, type and size of denuded areas of subchondral bone in the knee as a function of radiographic stage of OA - data from the OA initiative.

OBJECTIVE: To assess the presence, location, type and size of denuded areas of subchondral bone (dAB) in the femorotibial joint, measured quantitatively with 3T MRI, in a large subset of OAI participants. METHODS: One knee of 633 subjects (250 men, 383 women, aged 61.7+/-9.6 y) were studied, spanning all radiographic osteoarthritis (OA) stages. dABs were determined quantitatively using segmentations of coronal FLASHwe images, representing areas where the subchondral bone was not covered by cartilage. Post hoc visual examination of segmented images determined whether dABs represented full thickness cartilage loss or internal osteophyte. RESULTS: 7% Of the knees were Kellgren & Lawrence (KL) grade 0, 6% grade 1, 41% grade 2, 41% grade 3, and 5% grade 4. 39% Of the participants (48% of the men and 33% of the women) displayed dABs; 61% of the dABs represented internal osteophytes. 1/47 Participants with KL grade 0 displayed 'any' dAB whereas 29/32 of the KL grade 4 knees were affected. Even as early as KL grade 1, 29% of the participants showed dABs. There were significant relationships of dAB with increasing KL grades (P<0.001) and with ipsi-compartimental JSN (P< or =0.001). Internal osteophytes were more frequent laterally (mainly posterior tibia and internal femur) whereas full thickness cartilage loss was more frequent medially (mainly external tibia and femur). CONCLUSIONS: dABs occur already at earliest stages of radiographic OA (KL grades 1 and 2) and become more common (and larger) with increasing disease severity. Almost all KL grade 4 knees exhibited dABs, with cartilage loss being more frequent than internal osteophytes.

MRI-detected subchondral bone marrow signal alterations of the knee joint: terminology, imaging appearance, relevance and radiological differential diagnosis.

OBJECTIVE: To discuss terminology, radiological differential diagnoses and significance of magnetic resonance imaging (MRI)-detected subchondral bone marrow lesions (BMLs) of the knee joint. METHODS: An overview of the published literature is presented. In addition, the radiological appearance and differential diagnosis of subchondral signal alterations of the knee joint are discussed based on expert consensus. A recommendation for terminology is provided and the relevance of these imaging findings for osteoarthritis (OA) research is emphasized. RESULTS: A multitude of differential diagnoses of subchondral BMLs may present with a similar aspect and signal characteristics. For this reason it is crucial to clearly and specifically define the type of BML that is being assessed and to use terminology that is appropriate to the condition and the pathology. In light of the currently used terminology, supported by histology, it seems appropriate to apply the widely used term "bone marrow lesion" to the different entities of subchondral signal alterations and in addition to specifically and precisely define the analyzed type of BML. Water sensitive sequences such as fat suppressed T2-weighted, proton density-weighted, intermediate-weighted fast spin echo or short tau inversion recovery (STIR) sequences should be applied to assess non-cystic BMLs as only these sequences depict the lesions to their maximum extent. Assessment of subchondral non-cystic ill-defined BMLs on gradient echo-type sequences should be avoided as they will underestimate the size of the lesion. Differential diagnoses of OA related BMLs include traumatic bone contusions and fractures with or without disruption of the articular surface. Osteonecrosis and bone infarcts, inflammation, tumor, transient idiopathic bone marrow edema, red marrow and post-surgical alterations should also be considered. CONCLUSION: Different entities of subchondral BMLs that are of relevance in the context of OA research may be distinguished by specific imaging findings, patient characteristics, symptoms, and history and are discussed in this review.

The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year.

OBJECTIVES: To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS: Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS: JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION: Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.