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Objective: Resistance training (RT) can improve whole muscle strength without increasing muscle fiber size or contractility. Neural adaptations, which lead to greater neural activation of muscle, may mediate some of these improvements, particularly in older adults, where motor neuron denervation is common. The purpose of this study was to explore the relationship of neural adaptations, as reflected by neural cell adhesion molecule (NCAM) expression, to improvements in (1) whole muscle strength and (2) muscle fiber size following RT in older adults with knee osteoarthritis. We performed whole muscle strength measurements and immunohistochemical analysis of fiber size, type, and NCAM expression before and after a 14-week RT program., Results: RT increased whole-muscle strength as measured by 1-repetition maximum (1-RM) leg press (P = 0.01), leg extension (P = 0.03), and knee extensor peak torque (P = 0.050), but did not alter NCAM expression. Greater NCAM expression in myosin heavy chain (MHC) II fibers was associated with greater whole muscle strength gains (knee extensor peak torque r = 0.93; P < 0.01) and greater MHC II fiber size (r = 0.79; P < 0.01). Our results suggest that training-induced NCAM expression, and neural adaptations more generally, may be important for RT-induced morphological and functional improvements in older adults. Trial registration NCT01190046.

High-intensity resistance exercise (REX) training increases physical capacity, in part, by improving muscle cell size and function. Moderate-intensity REX, which is more feasible for many older adults with disease and/or disability, also increases physical function, but the mechanisms underlying such improvements are not understood. Therefore, we measured skeletal muscle structure and function from the molecular to the tissue level in response to 14 wk of moderate-intensity REX in physically inactive older adults with knee osteoarthritis ( n = 17; 70 ± 1 yr). Although REX training increased quadriceps muscle cross-sectional area (CSA), average single-fiber CSA was unchanged because of reciprocal changes in myosin heavy chain (MHC) I and IIA fibers. Intermyofibrillar mitochondrial content increased with training because of increases in mitochondrial size in men, but not women, with no changes in subsarcolemmal mitochondria in either sex. REX increased whole muscle contractile performance similarly in men and women. In contrast, adaptations in single-muscle fiber force production per CSA (i.e., tension) and contractile velocity varied between men and women in a fiber type-dependent manner, with adaptations being explained at the molecular level by differential changes in myosin-actin cross-bridge kinetics and mechanics and single-fiber MHC protein expression. Our results are notable compared with studies of high-intensity REX because they show that the effects of moderate-intensity REX in older adults on muscle fiber size/structure and myofilament function are absent or modest. Moreover, our data highlight unique sex-specific adaptations due to differential cellular and subcellular structural and functional changes. NEW & NOTEWORTHY Moderate-intensity resistance training causes sex-specific adaptations in skeletal muscle structure and function at the cellular and molecular levels in inactive older adult men and women with knee osteoarthritis. However, these responses were minimal compared with high-intensity resistance training. Thus adjuncts to moderate-intensity training need to be developed to correct underlying cellular and molecular structural and functional deficits that are at the root of impaired physical function in this mobility-limited population., (Copyright © 2017 the American Physiological Society.)

In older adults, we examined the effect of chronic muscle disuse on skeletal muscle structure at the tissue, cellular, organellar, and molecular levels and its relationship to muscle function. Volunteers with advanced-stage knee osteoarthritis (OA, n = 16) were recruited to reflect the effects of chronic lower extremity muscle disuse and compared with recreationally active controls (n = 15) without knee OA but similar in age, sex, and health status. In the OA group, quadriceps muscle and single-fiber cross-sectional area were reduced, with the largest reduction in myosin heavy chain IIA fibers. Myosin heavy chain IIAX fibers were more prevalent in the OA group, and their atrophy was sex-specific: men showed a reduction in cross-sectional area, and women showed no differences. Myofibrillar ultrastructure, myonuclear content, and mitochondrial content and morphology generally did not differ between groups, with the exception of sex-specific adaptations in subsarcolemmal (SS) mitochondria, which were driven by lower values in OA women. SS mitochondrial content was also differently related to cellular and molecular functional parameters by sex: greater SS mitochondrial content was associated with improved contractility in women but reduced function in men. Collectively, these results demonstrate sex-specific structural phenotypes at the cellular and organellar levels with chronic disuse in older adults, with novel associations between energetic and contractile systems., (Copyright © 2015 the American Physiological Society.)

Background: Previous studies of concomitant meniscal injury in athletes with anterior cruciate ligament (ACL) injury have examined age, sex, body mass index (BMI), injury mechanism, and time from injury to surgery as potential risk factors. Purpose: To identify additional risk factors for concomitant meniscal injury, including preinjury joint laxity and lower extremity alignment, in athletes with sport-related ACL injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study included 180 participants aged 13 to 26 years who underwent ACL reconstruction (ACLR) after a first-time ACL injury sustained during participation in sport. Contralateral lower extremity alignment and joint laxity were used as surrogate measures for the injured knee before trauma. Concomitant meniscal tear patterns were identified at the time of ACLR. Sex-specific analyses were conducted. Results: Concomitant meniscal injury was observed in 60.6% of the subjects. The prevalence of concomitant injury was higher in male than female participants (69.9% vs 54.2%; P =.035) due to a higher prevalence of lateral meniscal injuries (56.2% vs 38.3%; P =.018). Among male patients, there was a significant difference in the prevalence of concomitant lateral meniscal tear according to sport participation (≥9 vs <9 h/week: 67.4% vs 35.7%; P =.032). Among male patients, the likelihood of concomitant injury to both the lateral and medial menisci increased by 28.8% for each 1-mm decrease in navicular drop. Among female patients, the likelihood of concomitant injury to the lateral meniscus increased by 15% per degree increase in genu recurvatum and 14% per degree decrease in standing quadriceps angle, with similar effects on the likelihood of concurrent injury to both the lateral and medial menisci. Conclusion: Measures of lower extremity alignment and genu recurvatum previously identified as risk factors for ACL injury were also associated with concomitant meniscal injury in female patients while other risk factors, including BMI and joint laxity, were not. Increased time spent participating in sport and navicular drop were associated with concomitant meniscal injury in male patients. [ABSTRACT FROM AUTHOR]

Background: A comprehensive understanding of the intrinsic risk factors for anterior cruciate ligament (ACL) disruption is important for identifying individuals at increased risk for suffering this trauma and developing interventions to mitigate risk. Hypothesis: A variety of risk factors predispose athletes to first-time, noncontact ACL injury and some of these differ between male and female athletes. Study Design: Prospective cohort study with nested case-control sampling. Level of Evidence: Level 2. Methods: Sport teams at 28 high schools and 8 colleges were monitored prospectively over 4 years, and 109 of 130 athletes who suffered their first noncontact ACL injury participated in the study. At the time of injury, matched control subjects were randomly selected from among the case's teammates and a total of 227 athletes participated. Demographic characteristics, joint laxity, lower extremity alignment, strength, and personality characteristics were measured. The association of each risk factor with injury risk was assessed by conditional logistic regression. Results: The risk factors that were associated with ACL injury in both male and female athletes included having a parent with prior ACL injury and increases of the following variables: body weight, anterior displacement of the tibia relative to the femur, genu recurvatum, and generalized joint laxity. Risk factors that are unique to female athletes included increased body mass index, increased trunk flexion strength, and prior non-ACL knee injury. The risk factors specific to male athletes were decreased standing quadriceps angle, decreased hip adduction strength, and chronic disease. Conclusion: A diverse set of risk factors predispose both male and female athletes to ACL injury, whereas others appear to be sex-specific. Clinical Relevance: Different approaches for assessing risk and preventing ACL injury are needed for male and female athletes. In addition, personalized prevention strategies may be needed to target the specific characteristics that place an individual at increased risk of suffering this trauma. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) trauma and ACL reconstruction (ACLR) are associated with the loss of strength and function of the muscles that span the knee joint. The underlying mechanism associated with this is not completely understood. Purpose: To determine whether the duration of tourniquet use during ACLR has an effect on knee extensor muscle contractile function and size at the cellular (ie, fiber) level 3 weeks after surgery and at the whole-muscle level at 6 months after surgery. Study Design: Descriptive laboratory study and case series; Level of evidence, 4. Methods: Study participants sustained an acute, first-time ACL injury. All participants underwent ACLR with the use of a tourniquet placed in a standardized location on the thigh; the tourniquet was inflated (pressure range, 250-275 mm Hg), and the time of tourniquet use during surgery was documented. Participants were evaluated 1 week before surgery (to measure patient function, strength, and subjective outcome with the Knee injury and Osteoarthritis Outcome Score [KOOS] and International Knee Documentation Committee [IKDC] score), at 3 weeks after ACLR surgery (to obtain muscle biopsy specimens of the vastus lateralis and assess muscle fiber cross-sectional area, contractile function, and mitochondrial content and morphometry), and at 6 months after ACLR (to evaluate patient function, strength, and subjective outcomes via KOOS and IKDC scores). Data were acquired on both the injured/surgical limb and the contralateral, normal side to facilitate the use of a within-subjects study design. Results are based on additional analysis of data acquired from previous research that had common entry criteria, treatments, and follow-up protocols. Results: At 3 weeks after ACLR, the duration of tourniquet use at the time of surgery did not explain the variation in single–muscle fiber contractile function or cross-sectional area (myosin heavy chain [MHC] I and II fibers) or subsarcolemmal and intermyofibrillar mitochondrial content or morphometry. At 6 months after ACLR, the duration of tourniquet use was not associated with the peak isometric and isokinetic torque measurements, patient function, or patient-reported outcomes. Conclusion: The duration of tourniquet use at the time of ACLR surgery did not explain variation in muscle fiber size, contractile function, or mitochondrial content at 3 weeks after surgery or strength of the quadriceps musculature or patient-reported function or quality of life at 6-month follow-up. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) injuries and reconstruction (ACLR) promote quadriceps muscle atrophy and weakness that can persist for years, suggesting the need for more effective rehabilitation programs. Whether neuromuscular electrical stimulation (NMES) can be used to prevent maladaptations in skeletal muscle size and function is unclear. Purpose: To examine whether early NMES use, started soon after an injury and maintained through 3 weeks after surgery, can preserve quadriceps muscle size and contractile function at the cellular (ie, fiber) level in the injured versus noninjured leg of patients undergoing ACLR. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients (n = 25; 12 men/13 women) with an acute, first-time ACL rupture were randomized to NMES (5 d/wk) or sham (simulated microcurrent electrical nerve stimulation; 5 d/wk) treatment to the quadriceps muscles of their injured leg. Bilateral biopsies of the vastus lateralis were performed 3 weeks after surgery to measure skeletal muscle fiber size and contractility. Quadriceps muscle size and strength were assessed 6 months after surgery. Results: A total of 21 patients (9 men/12 women) completed the trial. ACLR reduced single muscle fiber size and contractility across all fiber types (P <.01 to P <.001) in the injured compared with noninjured leg 3 weeks after surgery. NMES reduced muscle fiber atrophy (P <.01) through effects on fast-twitch myosin heavy chain (MHC) II fibers (P <.01 to P <.001). NMES preserved contractility in slow-twitch MHC I fibers (P <.01 to P <.001), increasing maximal contractile velocity (P <.01) and preserving power output (P <.01), but not in MHC II fibers. Differences in whole muscle strength between groups were not discerned 6 months after surgery. Conclusion: Early NMES use reduced skeletal muscle fiber atrophy in MHC II fibers and preserved contractility in MHC I fibers. These results provide seminal, cellular-level data demonstrating the utility of the early use of NMES to beneficially modify skeletal muscle maladaptations to ACLR. Clinical Relevance: Our results provide the first comprehensive, cellular-level evidence to show that the early use of NMES mitigates early skeletal muscle maladaptations to ACLR. Registration: NCT02945553 (ClinicalTrials.gov identifier) [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: The incidence of contralateral anterior cruciate ligament (CACL) injuries after recovery from a first-time anterior cruciate ligament (ACL) disruption is high in women; however, little is known about the risk factors associated with this trauma. Hypothesis: Patient characteristics, strength, anatomic alignment, and neuromuscular characteristics of the contralateral uninjured leg at the time of the first ACL trauma are associated with risk of subsequent CACL injury, and these risk factors are distinct from those for a first-time ACL injury. Study Design: Case-control study; Level of evidence, 3. Methods: Sixty-one women who suffered a first-time noncontact ACL injury while participating in high school or college sports and underwent measurement of potential risk factors on their contralateral limb soon after the initial ACL injury and before reconstruction were followed until either a CACL injury or an ACL graft injury occurred, or until the last date of contact. Results: Follow-up information was available for 55 (90.0%) of the 61 athletes and 11 (20.0%) suffered a CACL injury. Younger age, decreased participation in sport before the first ACL disruption, decreased anterior stiffness of the contralateral knee, and increased hip anteversion were associated with increases in the risk of suffering a CACL injury. Conclusion: A portion of CACL injury risk factors were modifiable (time spent participating in sport and increasing anterior knee stiffness with bracing), while others were nonmodifiable (younger age and increased hip anteversion). The relationship between younger age at the time of an initial ACL injury and increased risk of subsequent CACL trauma may be explained by younger athletes having more years available to be exposed to at-risk activities compared with older athletes. A decrease of anterior stiffness of the knee is linked to decreased material properties and width of the ACL, and this may explain why some women are predisposed to bilateral ACL trauma while others only suffer the index injury. The risk factors for CACL injury are unique to women who suffer bilateral ACL trauma compared with those who suffer unilateral ACL trauma. This information is important for the identification of athletes who may benefit from risk reduction interventions. [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]

Background: Anterior cruciate ligament (ACL) graft rupture occurs at a high rate, especially in young athletes. The geometries of the tibial plateau and femoral intercondylar notch are risk factors for first-time ACL injury; however, little is known about the relationship between these geometries and risk of ACL graft rupture. Hypothesis: The geometric risk factors for noncontact graft rupture are similar to those previously identified for first-time noncontact ACL injury, and sex-specific differences exist. Study Design: Case-control study; Level of evidence, 3. Methods: Eleven subjects who suffered a noncontact ACL graft rupture and 44 subjects who underwent ACL reconstruction but did not experience graft rupture were included in the study. Using magnetic resonance imaging, the geometries of the tibial plateau subchondral bone, articular cartilage, meniscus, tibial spines, and femoral notch were measured. Risk factors associated with ACL graft rupture were identified using Cox regression. Results: The following were associated with increased risk of ACL graft injury in males: increased posterior-inferior–directed slope of the articular cartilage in the lateral tibial plateau measured at 2 locations (hazard ratio [HR] = 1.50, P = .029; HR = 1.39, P = .006), increased volume (HR = 1.45, P = .01) and anteroposterior length (HR = 1.34, P = .0023) of the medial tibial spine, and increased length (HR = 1.18, P = .0005) and mediolateral width (HR = 2.19, P = .0004) of the lateral tibial spine. In females, the following were associated with increased risk of injury: decreased volume (HR = 0.45, P = .02) and height (HR = 0.46, P = .02) of the medial tibial spine, decreased slope of the lateral tibial subchondral bone (HR = 0.72, P = .01), decreased height of the posterior horn of the medial meniscus (HR = 0.09, P = .001), and decreased intercondylar notch width at the anterior attachment of the ACL (HR = 0.72, P = .02). Conclusion: The geometric risk factors for ACL graft rupture are different for males and females. For females, a decreased femoral intercondylar notch width and a decreased height of the posterior medial meniscus were risk factors for ACL graft rupture that have also been found to be risk factors for first-time injury. There were no risk factors in common between ACL graft injury and first-time ACL injury for males. [ABSTRACT FROM AUTHOR]

Background: Multivariate analysis that identifies the combination of risk factors associated with anterior cruciate ligament (ACL) trauma is important because it provides insight into whether a variable has a direct causal effect on risk or an indirect effect that is mediated by other variables. It can also reveal risk factors that might not be evident in univariate analyses; if a variable’s effect is moderated by other variables, its association with risk may be apparent only after adjustment for the other variables. Most important, multivariate analyses can identify combinations of risk factors that are more predictive of risk than individual risk factors. Hypothesis: A diverse combination of risk factors predispose athletes to first-time noncontact ACL injury, and these relationships are different for male and female athletes. Study Design: Case-control study; Level of evidence, 3. Methods: Athletes competing in organized sports at the high school and college levels participated in this study. Data from injured subjects (109 suffering an ACL injury) and matched controls (227 subjects) from the same athletic team were analyzed with multivariate conditional logistic regression to examine the effects of combinations of variables (demographic characteristics, joint laxity, lower extremity alignment, strength, and personality traits) on the risk of suffering their first ACL injury and to construct risk models. Results: For male athletes, increases in anterior-posterior displacement of the tibia relative to the femur (knee laxity), posterior knee stiffness, navicular drop, and a decrease in standing quadriceps angle were jointly predictive of suffering an ACL injury. For female athletes the combined effects of having a parent who had suffered an ACL injury and increases in anterior-posterior knee laxity and body mass index were predictive of ACL injury. Conclusion: Multivariate models provided more information about ACL injury risk than individual risk factors. Both male and female risk models included increased anterior-posterior knee laxity as a predictor of ACL injury but were otherwise dissimilar. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated femoral intercondylar notch morphometry in patients with first-time noncontact anterior cruciate ligament (ACL) injury. Topics explored include the use of magnetic resonance imaging (MRI) data of participating ACL-injured patients, the outcome of the femoral notch measurement process, and the comparative analysis of femoral notch morphometry and ACL geometry.

The article discusses a study on 176 athletes that determined the association of higher posterior-inferior medial and lateral tibial plateau directed slope with higher risks for noncontact anterior cruciate ligament (ACL) injury. Obtained were magnetic resonance images (MRIs) of subjects and the characterization of subchondral bone part in tibial plateau, coronal tibial slope and medial tibial plateau depth. Results showed 21.7% higher risk in females of noncontact ACL injury than in males.

ABSTRACT 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. J Orthop Res 32:61-68, 2014. [ABSTRACT FROM AUTHOR]

The article presents a cohort study that assessed the association of patient, functional, and clinical outcomes and type II collagen metabolism with abnormal tibiofemoral joint space width (JSW). It included patients suffering from anterior cruciate ligament (ACL) disruptions. Evidence showed that ACL injured patients with an abnormal tibiofemoral JSW were discovered with diminished quality of life, increased pain, and increased type II collagen.

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from −5.6 to −1.7 ms for T1ρ, and −2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit. [ABSTRACT FROM AUTHOR]