Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury.

The present study measured early-stage adaptation of bone mineral (BMD) in the periarticular cancellous bone of the canine knee (stifle) joint after anterior cruciate ligament (ACL) transection (ACLX). Regional changes in BMD in the tibia and femur were analyzed by using quantitative computed tomography (qCT) at 3 wk and 12 wk after unilateral ACLX to determine whether there were focal points for BMD changes and whether these changes occurred early after the induced knee injury. BMD decreased rapidly after ACLX, and the more pronounced response was in the femur. In the 3-wk group, there were decreases in BMD in the tibia and the femur, and these changes were significant in the posterior-medial region of the femur, which showed a decrease of BMD in the ACLX limb (-0.048 +/- 0.011 g/cm(3)). In the 12-wk group, all regions in the tibia and femur exhibited significant decreases in BMD, and the average decrease was greatest in the posterior-medial region of the femur (-0.142 +/- 0.021 g/cm(3)). The regions of pronounced periarticular cancellous BMD adaptation corresponded to observed focal cartilage defects. Early decreases in BMD in the injured knee may be related to altered loading and kinematics in the knee and may be an important link in the pathogenesis of posttraumatic osteoarthritis.     

Doxycycline effects on mechanical and morphometrical properties of early- and late-stage osteoarthritic bone following anterior cruciate ligament injury.

As posttraumatic osteoarthritis (OA) progresses, the mechanical and morphometrical properties of the subchondral bone change and may be linked to damage of the articular cartilage. Potentially to slow that progression, doxycycline was administered orally twice daily (4 mg.kg(-1).day(-1)) in skeletally mature canines after anterior cruciate ligament transection (ACLX). To test if doxycycline significantly altered the structure and function of OA bone, we tested cancellous bone mechanical properties, measured bone mineral content, and analyzed bone structure by microcomputed tomography. Our investigation focused on subchondral trabecular bone changes in the medial femoral condyle at 36 and 72 wk after ACLX. Significant mechanical changes discovered at 36 wk post-ACLX were less obvious at 72 wk in both treated and ACLX groups. Doxycycline treatment conserved bone strain energy density at 72 wk. Doxycycline had little effect on the degradation of superficial osseous tissue at 36 wk post-ACLX; by 72 wk, doxycycline in an ACLX model limited subchondral bone loss within the first 3 mm of periarticular bone with established OA. Significant bone loss occurred in the deeper trabecular bone for all groups. Substantial architectural adaptation within deeper trabecular bone accompanied changes in mechanics in early and established OA.     

Physiological and mechanical adaptation of periarticular cancellous bone after joint ligament injury.

The relation between blood flow and bone mineral density (BMD) of periarticular bone was examined in an in vivo model of joint instability. Eighty mature New Zealand White rabbits were randomly assigned to experimental [anterior cruciate ligament transection (ACLX)], sham-operated control, or age-matched normal control groups. Experimental rabbits underwent unilateral transection of the right anterior cruciate ligament, and the nonoperated left [contralateral (Cntra)] limb was a within-animal control. BMD and blood flow to the periarticular bone in the femoral condyles were assessed in each group at 2, 4, 6, 14, and 48 wk postsurgery, using quantitative computed tomography scanning and entrapment of colored microspheres. BMD was significantly lower (5%) in the ACLX compared with Cntra limbs. Periarticular bone blood flow in the ACLX limbs was significantly greater than in the Cntra limb (29%) in the early stages (6 wk) after injury. Up to 48 wk post-ACLX, a significant correlation was found between increased blood flow and decreased BMD in the periarticular bone of the femoral condyles in the ACLX limbs. This correlation suggested that heightened blood flow may be linked to mechanisms of bone adaptation in joints after ligament injury.     

Analyses of dynamic co-contraction level in individuals with anterior cruciate ligament injury.

BACKGROUND: A complete understanding of neural mechanisms by which ligament receptors may contribute to joint stability is not well established. It has been suggested that these receptors may be involved in a neuromuscular process related to the modulation of dynamic co-contraction, as a means of guaranteeing functional joint stability. HYPOTHESIS: Individuals with ACL injury have diminished dynamic co-contraction. STUDY DESIGN: Exploratory, cross-sectional design. METHODS: Ten subjects with unilateral ACL injury treated conservatively, and ten subjects without history of injury participated in the study. The co-contraction level was assessed through EMG recordings of the vastus lateralis and biceps femoris before and after a perturbation imposed on the subjects during a walking task. RESULTS: Subjects with ACL injury presented significantly lower co-contraction level pre-perturbation (p = 0.045) and post-perturbation (p = 0.046) than those in the control group. CONCLUSIONS: The bilateral decrease in muscular co-contraction presented by individuals with ACL injury suggests that ligament and joint receptors may be responsible for a bilateral dynamic increase in muscle and joint stiffness that could result in a greater joint stability. CLINICAL RELEVANCE: This study analyzed a neuromuscular mechanism that might contribute to the functional stability of the knee joint.     

Rationale and implementation of anterior cruciate ligament injury prevention warm-up programs in female athletes

The sex disparity in anterior cruciate ligament (ACL) injury risk and the subsequent adverse effects on knee joint health, psychosocial well-being, and financial costs incurred have produced a surge in research on risk factors and interventions designed to decrease this disparity and overall incidence. Biomechanical and neuromuscular differences have been identified throughout the trunk and lower extremity that may increase noncontact ACL injury risk in female athletes. Evidence demonstrates that many risk factors are modifiable with intervention programs and that athletic performance measures can be enhanced. No universally accepted ACL injury prevention program currently exists, and injury prevention programs are diverse. Anterior cruciate ligament injury prevention programs introduced in a warm-up format offer multiple benefits, primarily, improved compliance based on improved practicality of implementation. However, drawbacks of warm-up style formats also exist, most notably that a lack of equipment and resources may preclude measurable improvements in athletic performance that foster improved compliance among participants. The purpose of this review is to analyze the current literature researching possible biomechanical and neuromuscular risk factors in noncontact ACL injury in female athletes and the most effective means of implementing critical elements of a program to decrease ACL injury risk in female athletes while improving athletic performance. Hip and hamstring training, core stabilization, plyometrics, balance, agility, neuromuscular training with video and verbal feedback to modify technique, and stretching appear to be essential components of these programs. Further research is critical to determine ideal training program volume, intensity, duration, and frequency.     

Human patellar tendon stiffness is restored following graft harvest for anterior cruciate ligament surgery

Minimising post-operative donor site morbidity is an important consideration when selecting a graft for surgical reconstruction of the torn anterior cruciate ligament (ACL). One of the most common procedures, the bone-patellar tendon-bone (BPTB) graft involves removal of the central third from the tendon. However, it is unknown whether the mechanical properties of the donor site (patellar tendon) recover. The present study investigated the mechanical properties of the human patellar tendon in 12 males (mean±S.D. age: 37±14 years) who had undergone surgical reconstruction of the ACL using a BPTB graft between 1 and 10 years before the study (operated knee; OP). The uninjured contralateral knee served as a control (CTRL). Patellar tendon mechanical properties were assessed in vivo combining dynamometry with ultrasound imaging. Patellar tendon stiffness was calculated from the gradient of the tendon's force–elongation curve. Tendon stiffness was normalised to the tendon's dimensions to obtain the tendon's Young's modulus. Cross-sectional area (CSA) of OP patellar tendons was larger by 21% than CTRL tendons (P<0.01). Patellar tendon stiffness was not significantly different between OP and CTRL tendons, but the Young's modulus was lower by 24% in OP tendons (P<0.01). A compensatory enlargement of the patellar tendon CSA, presumably due to scar tissue formation, enabled a recovery of tendon stiffness in the OP tendons. The newly formed tendon tissue had inferior properties as indicated by the reduced tendon Young's modulus, but it increased to a level that enabled recovery of tendon stiffness.     

Fatigue injury risk in anterior cruciate ligament of target side knee during golf swing

A golf-related ACL injury can be linked with excessive golf play or practice because such over-use by repetitive golf swing motions can increase damage accumulation to the ACL bundles. In this study, joint angular rotations, forces, and moments, as well as the forces and strains on the ACL of the target-side knee joint, were investigated for ten professional golfers using the multi-body lower extremity model. The fatigue life of the ACL was also predicted by assuming the estimated ACL force as a cyclic load. The ACL force and strain reached their maximum values within a short time just after ball-impact in the follow-through phase. The smaller knee flexion, higher internal tibial rotation, increase of the joint compressive force and knee abduction moment in the follow-through phase were shown as to lead an increased ACL loading. The number of cycles to fatigue failure (fatigue life) in the ACL might be several thousands. It is suggested that the excessive training or practice of swing motion without enough rest may be one of factors to lead to damage or injury in the ACL by the fatigue failure. The present technology can provide fundamental information to understand and prevent the ACL injury for golf players.     

The effects of knee joint kinematics on anterior cruciate ligament injury and articular cartilage damage

This study determined which knee joint motions lead to anterior cruciate ligament (ACL) rupture with the knee at 25° of flexion. The knee was subjected to internal and external rotations, as well as varus and valgus motions. A failure locus representing the relationship between these motions and ACL rupture was established using finite element simulations. This study also considered possible concomitant injuries to the tibial articular cartilage prior to ACL injury. The posterolateral bundle of the ACL demonstrated higher rupture susceptibility than the anteromedial bundle. The average varus angular displacement required for ACL failure was 46.6% lower compared to the average valgus angular displacement. Femoral external rotation decreased the frontal plane angle required for ACL failure by 27.5% compared to internal rotation. Tibial articular cartilage damage initiated prior to ACL failure in all valgus simulations. The results from this investigation agreed well with other experimental and analytical investigations. This study provides a greater understanding of the various knee joint motion combinations leading to ACL injury and articular cartilage damage.     

Neuromuscular function after anterior cruciate ligament reconstruction with autologous semitendinosus-gracilis graft.

BACKGROUND: The quadrupled autologous semitendinosus-gracilis graft is the first choice of many orthopaedic surgeons when reconstructing the anterior cruciate ligament. The effect that this procedure has on voluntary muscle control remains unclear. The purpose of this study was to evaluate the effect that anterior cruciate ligament reconstruction with autologous semitendinosus-gracilis graft has on voluntary muscle control by assessing subjects' specificity of muscle action. METHODS: The voluntary muscle control of 10 people (seven males, three females) with acute, isolated ACL ruptures was assessed in the days prior to when they underwent anterior cruciate ligament reconstruction with quadrupled autologous semitendinosus-gracilis grafts and after they had returned to play in sports requiring quick changes of direction and jumping (approximately 6 months later). The experimental protocol included the use of an established target-matching protocol that requires subjects to produce and modulate force with fine control, electromyographic recordings from 11 muscles about the knee, and the use of circular statistics to calculate specificity indices that describe the degree of focus (specificity) associated with the activity pattern of each muscle. Data were analyzed by performing pre-surgery and post-return to sports side-to-side comparisons, as well as, pre-surgery to post-surgery ipsilateral comparisons. RESULTS: Diminished specificity of muscle action was observed in the activity patterns of most of the muscles of the subjects' anterior cruciate ligament deficient knees prior to surgery. The quadriceps muscles were particularly affected. Post-return to sports results indicated that voluntary muscle control had improved in most muscles. There was no significant difference in pre-surgery and post-return to sports semitendinosus and gracilis muscle control. The semimembranosus muscle displayed less specific muscle activity patterns following surgery, which may represent a compensation strategy for minor changes in neuromuscular function. CONCLUSIONS: Voluntary muscle control improved in most muscles following ACL reconstruction with semitendinosus-gracilis autografts. Semitendinosus and gracilis muscle control did not appear to be altered significantly by the procedure.     

Location-dependent variations in the material properties of the anterior cruciate ligament.

Our recent anterior drawer studies in human cadaveric knees [Guan and Butler, Adv. Bioengng 17, 5 (1990); Guan et al., Trans. orthop. Res. Soc. 16, 589 (1991)] have suggested that anterior bundles of the anterior cruciate ligament (ACL) develop higher load-related material properties than posterior bundles. This was confirmed when we reevaluated the axial failure data for these bundle-bone specimens from an earlier study [Butler et al., J. Biomechanics 19, 425-432 (1986)]. The purpose of this study was to determine, in a larger data set, if anteromedial and anterolateral bundles of the anterior cruciate ligament exhibit significantly larger load-related material properties than the posterior ligament bundles. Seven ACL-bone units from seven donors (the three tissues from the original study plus four new ones) were subdivided into three subunits, preserving the bone insertions. The subunits were failed in tension at a constant strain rate (100% s-1) and four material properties were compared within and between donors. The anterior bundles developed significantly larger moduli, maximum stresses, and strain energy densities to maximum stress than the posterior subunits. Moduli for the anterior vs posterior subunits averaged 284 MPa vs 155 MPa, maximum stresses averaged 38 MPa vs 15 MPa, and strain energy densities averaged 2.7 N m cc-1 vs 1.1 N m cc-1, respectively. No significant differences were found, however, among strains to maximum stress or between any of the other properties for the two anterior subunits. These results are important to the design of ligament replacements and suggest new experiments designed to distinguish in vivo force levels in these ACL bands, a possible reason for the material differences.     

Effect of testosterone on the female anterior cruciate ligament

Injuries to the anterior cruciate ligament (ACL) result in immediate and long-term morbidity and expense. Young women are more likely to sustain ACL injuries than men who participate in similar athletic and military activities. Although significant attention has focused on the role that female sex hormones may play in this disparity, it is still unclear whether the female ACL also responds to androgens. The purpose of this study was to determine whether the female ACL was an androgen-responsive tissue. To identify and localize androgen receptors in the female ACL, we used Western blotting and immunofluorescent labeling, respectively, of ACL tissue harvested during surgery from young women (n = 3). We then measured ACL stiffness and assessed total testosterone (T) and free [free androgen index (FAI)] testosterone concentrations, as well as relative estradiol to testosterone ratios (E(2)/T and E(2)/FAI) at three consecutive menstrual stages (n = 20). There were significant rank-order correlations between T (0.48, P = 0.031), FAI (0.44, P = 0.053), E(2)/T (-0.71, P < 0.001), E(2)/FAI (-0.63, P = 0.003), and ACL stiffness near ovulation. With the influences of the other variables controlled, there were significant negative partial rank-order correlations between ACL stiffness and E(2)/T (-0.72, P < 0.001) and E(2)/FAI (-0.59, P = 0.012). The partial order residuals for T and FAI were not significant. These findings suggest that the female ACL is an androgen-responsive tissue but that T and FAI are not independent predictors of ACL stiffness near ovulation. Instead, the relationship between T, FAI, and ACL stiffness was likely influenced by another hormone or sex hormone binding globulin.     

Pattern of anterior cruciate ligament force in normal walking

The goal of this study was to calculate and explain the pattern of anterior cruciate ligament (ACL) loading during normal level walking. Knee-ligament forces were obtained by a two-step procedure. First, a three-dimensional (3D) model of the whole body was used together with dynamic optimization theory to calculate body-segmental motions, ground reaction forces, and leg-muscle forces for one cycle of gait. Joint angles, ground reaction forces, and muscle forces obtained from the gait simulation were then input into a musculoskeletal model of the lower limb that incorporated a 3D model of the knee. The relative positions of the femur, tibia, and patella and the forces induced in the knee ligaments were found by solving a static equilibrium problem at each instant during the simulated gait cycle. The model simulation predicted that the ACL bears load throughout stance. Peak force in the ACL (303 N) occurred at the beginning of single-leg stance (i.e., contralateral toe off). The pattern of ACL force was explained by the shear forces acting at the knee. The balance of muscle forces, ground reaction forces, and joint contact forces applied to the leg determined the magnitude and direction of the total shear force acting at the knee. The ACL was loaded whenever the total shear force pointed anteriorly. In early stance, the anterior shear force from the patellar tendon dominated the total shear force applied to the leg, and so maximum force was transmitted to the ACL at this time. ACL force was small in late stance because the anterior shear forces supplied by the patellar tendon, gastrocnemius, and tibiofemoral contact were nearly balanced by the posterior component of the ground reaction.     

Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model

Introduction

The aim of this prospective, randomized, controlled, double-blind study was to evaluate the effects of tiludronate (TLN), a bisphosphonate, on structural, biochemical and molecular changes and function in an experimental dog model of osteoarthritis (OA).

Methods

Baseline values were established the week preceding surgical transection of the right cranial/anterior cruciate ligament, with eight dogs serving as OA placebo controls and eight others receiving four TLN injections (2 mg/kg subcutaneously) at two-week intervals starting the day of surgery for eight weeks. At baseline, Week 4 and Week 8, the functional outcome was evaluated using kinetic gait analysis, telemetered locomotor actimetry and video-automated behaviour capture. Pain impairment was assessed using a composite numerical rating scale (NRS), a visual analog scale, and electrodermal activity (EDA). At necropsy (Week 8), macroscopic and histomorphological analyses of synovium, cartilage and subchondral bone of the femoral condyles and tibial plateaus were assessed. Immunohistochemistry of cartilage (matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS5)) and subchondral bone (cathepsin K) was performed. Synovial fluid was analyzed for inflammatory (PGE₂ and nitrite/nitrate levels) biomarkers. Statistical analyses (mixed and generalized linear models) were performed with an α-threshold of 0.05.

Results

A better functional outcome was observed in TLN dogs than OA placebo controls. Hence, TLN dogs had lower gait disability (P = 0.04 at Week 8) and NRS score (P = 0.03, group effect), and demonstrated behaviours of painless condition with the video-capture (P < 0.04). Dogs treated with TLN demonstrated a trend toward improved actimetry and less pain according to EDA. Macroscopically, both groups had similar level of morphometric lesions, TLN-treated dogs having less joint effusion (P = 0.01), reduced synovial fluid levels of PGE₂ (P = 0.02), nitrites/nitrates (P = 0.01), lower synovitis score (P < 0.01) and a greater subchondral bone surface (P < 0.01). Immunohistochemical staining revealed lower levels in TLN-treated dogs of MMP-13 (P = 0.02), ADAMTS5 (P = 0.02) in cartilage and cathepsin K (P = 0.02) in subchondral bone.

Conclusion

Tiludronate treatment demonstrated a positive effect on gait disability and joint symptoms. This is likely related to the positive influence of the treatment at improving some OA structural changes and reducing the synthesis of catabolic and inflammatory mediators.     

An implantable transducer for measuring tension in an anterior cruciate ligament graft.

The goal of this study was to develop a new implantable transducer for measuring anterior cruciate ligament (ACL) graft tension postoperatively in patients who have undergone ACL reconstructive surgery. A unique approach was taken of integrating the transducer into a femoral fixation device. To devise a practical in vivo calibration protocol for the fixation device transducer (FDT), several hypotheses were investigated: (1) The use of a cable versus the actual graft as the means for applying load to the FDT during calibration has no significant effect on the accuracy of the FDT tension measurements; (2) the number of flexion angles at which the device is calibrated has no significant effect on the accuracy of the FDT measurements; (3) the friction between the graft and femoral tunnel has no significant effect on measurement accuracy. To provide data for testing these hypotheses, the FDT was first calibrated with both a cable and a graft over the full range of flexion. Then graft tension was measured simultaneously with both the FDT on the femoral side and load cells, which were connected to the graft on the tibial side, as five cadaver knees were loaded externally. Measurements were made with both standard and overdrilled tunnels. The error in the FDT tension measurements was the difference between the graft tension measured by the FDT and the load cells. Results of the statistical analyses showed that neither the means of applying the calibration load, the number of flexion angles used for calibration, nor the tunnel size had a significant effect on the accuracy of the FDT. Thus a cable may be used instead of the graft to transmit loads to the FDT during calibration, thus simplifying the procedure. Accurate calibration requires data from just three flexion angles of 0, 45, and 90 deg and a curve fit to obtain a calibration curve over a continuous range of flexion within the limits of this angle group. Since friction did not adversely affect the measurement accuracy of the FDT, the femoral tunnel can be drilled to match the diameter of the graft and does not need to be overdrilled. Following these procedures, the error in measuring graft tension with the FDT averages less than 10 percent relative to a full-scale load of 257 N.     

Results of the surgical reconstruction of the anterior cruciate ligament

Results of the surgical reconstruction of the anterior cruciate ligament (ACL), using as a graft fourfold hamstring tendons (gracilis and semitendinosus) and middle third of the patellar ligament, were compared. In all patients that were participating in this study clinical examination and magnetic resonance showed ACL rupture, and apart from the choice of the graft, surgical technique was identical. We evaluated 112 patients with implemented patellar ligament graft and fourfold hamstring tendons graft six months after the procedure. Both groups were similar according to age, sex, activity level, knee instability level and rehabilitation program. The results showed that there was no significant difference between groups regarding Lysholm Knee score, IKDC 2000 score, activity level, musculature hypotrophy, and knee joint stability 6 months after the surgery. Anterior knee pain incidence is significantly higher in the group with patellar ligament graft (44% vs. 21%). Both groups had a significant musculature hypotrophy of the upper leg of the knee joint that was surgically treated, six months after the procedure. Both grafts showed good subjective and objective results.     

Estimation of forces on anterior cruciate ligament in dynamic activities

Biomechanics and Modeling in Mechanobiology - In this work, a nonlinear strain rate dependent plugin developed for the OpenSim® platform was used to estimate the instantaneous strain rate...     

Overrepresentation of the COL3A1 AA genotype in Polish skiers with anterior cruciate ligament injury

Although various intrinsic and extrinsic risk factors for anterior cruciate ligament (ACL) rupture have been identified, the exact aetiology of the injury is not yet fully understood. Type III collagen is an important factor in the repair of connective tissue, and certain gene polymorphisms may impair the tensile strength. The aim of this study was to examine the association of the COL3A1 rs1800255 polymorphism with ACL rupture in Polish male recreational skiers. A total of 321 male Polish recreational skiers were recruited for this study; 138 had surgically diagnosed primary ACL ruptures (ACL-injured group) and 183 were apparently healthy male skiers (control group – CON) who had no self-reported history of ligament or tendon injury. Both groups had a comparable level of exposure to ACL injury. Genomic DNA was extracted from the oral epithelial cells. All samples were genotyped on a real-time polymerase chain reaction instrument. The genotype distribution in the ACL-injured group was significantly different than in CON (respectively: AA=10.1 vs 2.2%, AG=22.5 vs 36.1, GG=67.4 vs 61.8%; p=0.0087). The AA vs AG+GG genotype of COL3A1 (odds ratio (OR)=5.05; 95% confidence interval (CI), 1.62-15.71, p=0.003) was significantly overrepresented in the ACL-injured group compared with CON. The frequency of the A allele was higher in the ACL-injured group (21.4%) compared with CON (20.2%), but the difference was not statistically significant (p=0.72). This study revealed an association between the COL3A1 rs1800255 polymorphism and ACL ruptures in Polish skiers.     

Antioxidant supplementation lowers circulating IGF-1 but not F2-isoprostanes immediately following anterior cruciate ligament surgery

Abstract

Interleukin (IL)-10 is an anti-inflammatory cytokine that suppresses pro-inflammatory cytokines. We previously demonstrated that supplementation with vitamins E and C ameliorated the increase in IL-10 immediately following anterior cruciate ligament (ACL) surgery in the absence of other cytokine perturbations. Since both oxidative stress and insulin-like growth factor-1 (IGF-1) can modulate IL-10 concentrations, the mechanisms for these changes warranted further investigation. Our objective was to evaluate the mechanism for the IL-10 decrease following ACL surgery. This study consisted of randomized, double-blind, placebo-controlled experimental design. Subjects were randomly assigned to daily supplementation with either: (i) antioxidants (AO; vitamins E [α-tocopherol] and C [ascorbic acid]; n = 10); or (ii) matching placebos (PL; n = 10). Supplementation started ～2 weeks prior to surgery (baseline) and concluded 3 months after surgery. Subjects provided six fasting blood samples at: (i) baseline; (ii) immediately pre-surgery (Pre); (iii) 90 min; (iv) 72 h; (v) 7 days; and (vi) 3 months post-surgery. α-Tocopherol, ascorbic acid, F₂-isoprostane and IGF-1 concentrations were measured in each blood sample. At 90 min relative to other times, plasma F₂-isoprostane concentrations were significantly (P < 0.05) elevated in both groups, while at 90 min IGF-1 was significantly (P < 0.05) lower in the AO compared to the PL group. The changes in IGF-1 at 90 min relative to baseline were correlated (P < 0.0001) with the changes in IL-10. The decrease in IL-10 observed in the AO group is likely dependent on the decrease IGF-1 since lipid peroxidation was unchanged between the two groups.