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Severe knee trauma, such as an ACL disruption, produces aggrecan degradation as evidenced by elevated synovial fluid (SF) N-terminal (393) Alanine-Arginine-Glycine-Serine (ARGS) neoepitope (or ARGS-aggrecan) and is associated with inflammatory activity soon after injury. However, it is not known if this process persists for a substantial time interval following the initial trauma. The purpose of this study was to evaluate relationships between SF ARGS concentrations and an array of cytokines, matrix metalloproteases (MMPs), and tissue inhibitor of metalloproteases (TIMPs) during the initial 6 months following ACL rupture. SF samples from 67 ACL-injured subjects (29 women) were analyzed within 6 months of injury (18-155 days), immediately prior to surgical ACL reconstruction. Relationships between ARGS and individual analyte concentrations, as well as MMP/TIMP ratios were evaluated. Statistically significant relationships were found between ARGS and basic fibroblast growth factor (FGF2) (p=0.03) and TIMP-3 (p=0.01). Our findings suggest that FGF2, considered to be primarily catabolic in articular cartilage, is not downregulated as ARGS concentration declines over time since injury. In addition, these results support the hypothesis that an upregulation of TIMP-3, the primary aggrecanase inhibitor, is elicited in response to increased aggrecan degradation, which may inhibit further cleavage., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Tibial plateau subchondral bone geometry has been associated with the risk of sustaining a non-contact ACL injury; however, little is known regarding the influence of the meniscus and articular cartilage interface geometry on risk. We hypothesized that geometries of the tibial plateau articular cartilage surface and meniscus were individually associated with the risk of non-contact ACL injury. In addition, we hypothesized that the associations were independent of the underlying subchondral bone geometry. MRI scans were acquired on 88 subjects that suffered non-contact ACL injuries (27 males, 61 females) and 88 matched control subjects that were selected from the injured subject's teammates and were thus matched on sex, sport, level of play, and exposure to risk of injury. Multivariate analysis of the female data revealed that increased posterior-inferior directed slope of the middle articular cartilage region and decreased height of the posterior horn of the meniscus in the lateral compartment were associated with increased risk of sustaining a first time, non-contact ACL injury, independent of each other and of the slope of the tibial plateau subchondral bone. No measures were independently related to risk of non-contact ACL injury among males., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Anterior cruciate ligament (ACL) injuries are disabling and are associated with the early onset of posttraumatic osteoarthritis. Little is known regarding the incidence rate of first-time noncontact ACL injuries sustained during athletic events and how they are independently influenced by level of competition, type of sport, and the participant's sex., Hypothesis: Level of competition (college or high school), type of sport (soccer, basketball, lacrosse, field hockey, football, rugby, volleyball), and the athlete's sex independently influence the incidence rate of first-time noncontact ACL injuries., Study Design: Cohort study; Level of evidence, 2., Methods: Between fall 2008 and spring 2012, first-time noncontact ACL injury data were collected from 8 colleges and 18 high schools across 7 sports. Athlete exposure was computed retrospectively using team rosters and numbers of scheduled practices and games. Injury incidence rates (IRs) were computed per 1000 athlete exposures. The independent effects of level of competition, sport, and sex on ACL injury risk were estimated by Poisson regression., Results: Colleges reported 48 ACL injuries with 320,719 athlete exposures across all sports studied (IR = 0.150 per 1000 person-days), while high schools reported 53 injuries with 873,057 athlete exposures (IR = 0.061). After adjustment for differences in sport and sex, college athletes had a significantly higher injury risk than did high school athletes (adjusted relative risk [RR], 2.38; 95% CI, 1.55-3.54). The overall IR for female athletes was 0.112 compared with 0.063 for males. After adjustment for sport and level of play, females were more than twice as likely to have a first-time ACL injury compared with males (RR, 2.10; 95% CI, 1.34-3.27). With lacrosse as the reference group, risk of first-time noncontact ACL injury was significantly higher for soccer players (RR, 1.77) and for rugby players (RR, 2.23), independent of level of play and sex., Conclusion: An athlete's risk of having a first-time noncontact ACL injury is independently influenced by level of competition, the participant's sex, and type of sport, and there are no interactions between their effects. Female college athletes have the highest risk of having a first-time noncontact ACL injury among the groups studied., (© 2014 The Author(s).)

Background: The morphometric characteristics of the anterior cruciate ligament (ACL) and the femoral intercondylar notch within which it resides have been implicated as risk factors for injuries to this important stabilizer of the knee. Prior research has produced equivocal results with differing methodologies, and consequently, it is unclear how these characteristics affect the injury risk in male and female patients., Hypothesis: The morphometric characteristics of the ACL and femoral intercondylar notch are individually and independently associated with the risk of suffering a noncontact ACL injury, and these relationships are different in male and female patients., Study Design: Case-control study; Level of evidence, 3., Methods: Magnetic resonance imaging scans of the bilateral knees were obtained on 88 case-control pairs (27 male, 61 female) matched for age, sex, and participation on the same sports team. Patients had suffered a grade III, first-time, noncontact ACL tear. The femoral notch width at 4 locations, the thickness of the bony ridge at the anteromedial outlet of the femoral notch, the femoral notch volume, ACL volume, and ACL cross-sectional area were measured., Results: Multivariate analysis of combined data from male and female patients revealed that decreased ACL volume (odds ratio [OR], 0.829), decreased femoral notch width (OR, 0.700), and increased bony ridge thickness at the anteromedial outlet of the femoral notch (OR, 1.614) were significant independent predictors of an ACL injury. Separate analyses of male and female patients indicated that the femoral notch ridge may be more strongly associated with a risk in female patients, while ACL volume is more strongly associated with a risk in male patients. However, statistical analysis performed with an adjustment for body weight strengthened the association between ACL volume and the risk of injuries in female patients., Conclusion: Morphometric features of both the ACL and femoral notch combine to influence the risk of suffering a noncontact ACL injury. When included together in a multivariate model that adjusts for body weight, the effects of the morphometric measurements are similar in male and female patients. If body weight is not taken into consideration, ACL volume is not associated with a risk in female patients., (© 2014 The Author(s).)

The purpose of this study was to determine if geometry of the articular surfaces of the tibial plateau is associated with non-contact anterior cruciate ligament (ACL) injury. This was a longitudinal cohort study with a nested case-control analysis. Seventy-eight subjects who suffered a non-contact ACL tear and a corresponding number of controls matched by age, sex, and sport underwent 3 T MRI of both knees. Surface geometry of the tibial articular cartilage was characterized with polynomial equations and comparisons were made between knees on the same person and between ACL-injured and control subjects. There was no difference in surface geometry between the knees of the control subjects. In contrast, there were significant differences in the surface geometry between the injured and normal knees of the ACL-injured subjects, suggesting that the ACL injury changed the cartilage surface profile. Therefore, comparisons were made between the uninjured knees of the ACL-injured subjects and the corresponding knees of their matched controls and this revealed significant differences in the surface geometry for the medial (p < 0.006) and lateral (p < 0.001) compartments. ACL-injured subjects tended to demonstrate a posterior-inferior directed orientation of the articular surface relative to the long axis of the tibia, while the control subjects were more likely to show a posterior-superior directed orientation., (© 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Progression of primary knee osteoarthritis (OA) is often quantified by measuring structural alterations of the joint such as those in tibiofemoral joint space width (JSW) over time. Limited information is available regarding changes that occur during the onset and progression of posttraumatic OA (PTOA) that are often associated with anterior cruciate ligament (ACL) injury. Furthermore, there is a paucity of information regarding JSW changes in healthy patients, making JSW interpretation challenging during early PTOA progression., Purpose: To evaluate tibiofemoral JSW after ACL injury, ACL reconstruction, and rehabilitation compared with healthy, matched controls., Study Design: Cohort study; Level of evidence, 2., Methods: A total of 39 ACL-injured patients and 32 matched controls were evaluated. Injured patients were assessed at presurgical baseline and after ACL reconstruction (mean follow-up, 46 months), as were controls. Bilateral, standing, fluoroscopy-assisted, and posterior-anterior metatarsal-phalangeal view knee radiographs were obtained at each visit and JSW was measured., Results: The JSW differences between knees in control patients were not significantly different and did not change over time. Baseline JSW differences in the ACL group were significantly different than in controls. Three patients (7.9% of total) had an increased JSW difference, and 1 patient (2.6%) had a decreased medial JSW difference. In the lateral compartment, 6 patients (15.8%) had a decreased JSW difference. At follow-up, 2 patients in the ACL group (5%) had a decreased medial JSW difference, and 3 (7.9%) had a significantly increased difference in relation to controls. Lateral compartment analyses revealed 7 (18.4%) patients with a significantly decreased JSW difference and no patients with an increased difference compared with controls., Conclusion: One third of ACL-injured knees underwent significant JSW change soon after injury; consequently, evaluation of within-knee JSW changes over time in ACL-injured patients may not be appropriate with a study based on case-control analysis. The JSWs in the healthy knee of ACL-injured patients do not change over time, allowing this knee to be used as a control for the injured knee. This is important when evaluating the earliest stages of PTOA after ACL injury, when patients are asymptomatic and intervention may be most beneficial.

Background: When landing from a jump, the production of increased intersegmental knee abduction moments and coupled valgus motions has been associated with an increased risk of suffering a noncontact anterior cruciate ligament (ACL) injury in one study. This research has led to the development of a clinic-based algorithm that utilizes measures of knee valgus motion, knee flexion range of motion, body mass, tibial length, and quadriceps-to-hamstring strength ratio data to predict the probability of a high knee abduction moment (pKAM) when landing from a jump in female athletes. The ability of this algorithm to identify athletes at increased risk of suffering ACL injury has not been assessed., Hypothesis: The pKAM is associated with ACL injury in female athletes., Study Design: Case-control study; Level of evidence, 3., Methods: This study was based on secondary analysis of data obtained from a previous investigation that focused on the use of the drop vertical jump (DVJ) test to assess the risk of ACL injury in female athletes. The DVJ screenings were performed on 1855 female high school and college athletes over 3 years. Knee valgus motion, knee flexion range of motion, and tibial length were measured from videos of the DVJ obtained during preseason screenings. Mass was measured using a physician's scale, and quadriceps-to-hamstring strength ratio was included using a surrogate value. These data were entered into the clinic-based algorithm that determined the pKAM. The association of pKAM with ACL injury was assessed using conditional logistic regression., Results: A total of 20 athletes sustained ACL injury and were matched with 45 uninjured control athletes who were recruited from the same teams. There was no relationship between the risk of suffering ACL injury and pKAM, as determined by the clinic-based algorithm., Conclusion: The pKAM was not associated with noncontact ACL injury in our group of injured athletes and matched controls.

Background: Detailed descriptions of meniscus and articular cartilage lesions associated with anterior cruciate ligament injury have not been presented in the literature. Our goal was to determine the associations between patient sex, age, and surgical delay and the frequency and location of meniscus and articular cartilage lesions seen at the time of the anterior cruciate ligament reconstruction., Methods: Data were obtained retrospectively from a database of 1209 consecutive patients undergoing anterior cruciate ligament reconstruction between 1988 and 2002. All knee cartilage, meniscus, and ligament injuries were documented on anatomic maps at the time of surgery, and the data were analyzed., Results: Meniscus injuries were identified in 722 (65%) of the 1104 patients who met the criteria for inclusion in the study. Female patients were less likely to have a meniscus injury than male patients were (56% compared with 71%), and male patients were more likely to have combined medial and lateral meniscus injuries than female patients were (20% compared with 11%). Patients with a surgical delay of less than three months were less likely to have a medial meniscus injury (8% compared with 19%). Femoral articular cartilage injuries were identified in 472 patients (43%). Patients who were twenty-five years of age or older were more likely to have multiple cartilage lesions throughout the knee (7.7% compared with 1.3%) and to have more isolated medial femoral condyle lesions (24.2% compared with 13.3%). Patients with a surgical delay of more than one year were more likely to have a lesion (60% compared with 47% for all others), and a surgical delay of more than one year resulted in a greater proportion of large and grade-3 lesions of the lateral femoral condyle. Female patients had a greater proportion of grade-1 lesions of the medial femoral condyle (29% compared with 16%), whereas male patients had a greater proportion of grade-3 and 4 lesions of the medial femoral condyle (49% compared with 35%). In patients who were thirty-five years of age or older, meniscus injuries were more frequent and were located more frequently on the medial side; femoral articular cartilage lesions were also located more frequently on the medial side., Conclusions: Increased age, male sex, and increased surgical delay all increase the frequency and severity of injuries of the meniscus and/or articular cartilage after an anterior cruciate ligament tear.

Anterior cruciate ligament injury and reconstruction (ACLR) affects articular cartilage thickness profiles about the tibial, femoral, and patellar surfaces; however, it's unclear whether the magnitudes of change in cartilage thickness, as well as the locations and areas over which these changes occur, differ between males and females. This is important to consider as differences exist between the sexes with regard to knee biomechanics, patellofemoral pain, and anatomic alignment, which influence risk of an index and repeated injury. Subjects underwent ACLR with a bone‐patella tendon‐bone autograft. At 4‐year follow‐up, they had asymptomatic knees; however, significant ACL injured‐to‐contralateral normal knee differences in articular cartilage thickness values were observed. Both thickening and thinning of cartilage occurred about the tibiofemoral and patellofemoral joints, relative to matched control subjects with normal knees. Further, the location of the areas and magnitudes of thickening and thinning were different between females and males. Thickening (swelling) of articular cartilage is an early finding associated with the onset of posttraumatic osteoarthritis (PTOA). Therefore, the increases in cartilage thickness that were observed in this cohort may represent early signs of the onset of PTOA that occur prior to the patient developing symptoms and radiographic evidence of this disease. The different locations of areas that underwent a change in cartilage thicknesses between males and females suggest that each sex responds differently to knee ligament trauma, reconstruction, rehabilitation, and return to activity, and indicates that sex‐specific analysis should be utilized in studies of PTOA. [ABSTRACT FROM AUTHOR]

Combined injury to the anterior cruciate ligament (ACL) and meniscus is associated with earlier onset and increased rates of post‐traumatic osteoarthritis compared with isolated ACL injury. However, little is known about the initial changes in joint structure associated with these different types of trauma. We hypothesized that trauma to the ACL and lateral meniscus has an immediate effect on morphometry of the articular cartilage and meniscus about the entire tibial plateau that is more pronounced than an ACL tear without meniscus injury. Subjects underwent magnetic resonance imaging scanning soon after injury and prior to surgery. Those that suffered injury to the ACL and lateral meniscus underwent changes in the lateral compartment (increases in the posterior–inferior directed slopes of the articular cartilage surface, and the wedge angle of the posterior horn of the meniscus) and medial compartment (the cartilage‐to‐bone height decreased in the region located under the posterior horn of the meniscus, and the thickness of cartilage increased and decreased in the mid and posterior regions of the plateau, respectively). Subjects that suffered an isolated ACL tear did not undergo the same magnitude of change to these articular structures. A majority of the changes in morphometry occurred in the lateral compartment of the knee; however, change in the medial compartment of the knee with a normal appearing meniscus also occurred. Statement of clinical significance: Knee injuries that involve combined trauma to the ACL and meniscus directly affect both compartments of the knee, even if the meniscus and articular cartilage appears normal upon arthroscopic examination. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:759‐767, 2020 [ABSTRACT FROM AUTHOR]

Background: Contralateral anterior cruciate ligament (CACL) injury after recovery from a first-time ACL rupture occurs at a high rate in young females; however, little is known about the risk factors associated with bilateral ACL trauma. Hypothesis: The geometric characteristics of the contralateral knee at the time of the initial ACL injury are associated with risk of suffering a CACL injury in these female athletes. Study Design: Case-control study; Level of evidence, 3. Methods: Sixty-two female athletes who suffered their first noncontact ACL injury while participating in sports at the high school or college level were identified, and geometry of the femoral notch, ACL, tibial spines, tibial subchondral bone, articular cartilage surfaces, and menisci of the contralateral, uninjured, knee was characterized in 3 dimensions. We were unable to contact 7 subjects and followed the remaining 55 until either a CACL injury or an ACL graft injury occurred or, if they were not injured, until the date of last contact (mean, 34 months after their first ACL injury). Cox regression was used to identify risk factors for CACL injury. Results: Ten (18.2%) females suffered a CACL injury. Decreases of 1 SD in femoral intercondylar notch width (measured at its outlet and anterior attachment of the ACL) were associated with increases in the risk of suffering a CACL injury (hazard ratio = 1.88 and 2.05, respectively). Likewise, 1 SD decreases in medial-lateral width of the lateral tibial spine, height of the medial tibial spine, and thickness of the articular cartilage located at the posterior region of the medial tibial compartment were associated with 3.59-, 1.75-, and 2.15-fold increases in the risk of CACL injury, respectively. Conclusion: After ACL injury, subsequent injury to the CACL is influenced by geometry of the structures that surround the ACL (the femoral notch and tibial spines). This information can be used to identify individuals at increased risk for CACL trauma, who might benefit from targeted risk-reduction interventions. [ABSTRACT FROM AUTHOR]