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1.
J ISAKOS ; 8(3): 145-152, 2023 06.
Article in English | MEDLINE | ID: mdl-36646171

ABSTRACT

The paediatric population is at particularly high risk for anterior cruciate ligament (ACL) injuries due to high rates of sports participation. Other risk factors for ACL injuries in children include but are not limited to being female, generalised ligamentous laxity, a high body mass index (BMI), and poor neuromuscular control. ACL reconstruction (ACLR) is commonly done to treat ACL injuries and allow for return to sports and daily activities. ACL repair is another option with ongoing techniques being developed. The high rates of graft failure in children reported in recent publications on ACL repair are very concerning. Special consideration must be taken in ACLR in the skeletally immature patient due to the risk of growth-related complications, such as limb deformity or growth arrest, that can arise from drilling across or disrupting the physis. Graft choices for paediatric ACLR include iliotibial band (ITB) over the top and over the front, hamstring autograft, bone patellar tendon bone (BTB) autograft, quadriceps tendon autograft, and allograft. Factors for each graft choice to consider include graft size, graft failure rates, donor site morbidity, requirement for bony tunnels, the post-op rehabilitation process, and return to sport outcomes. Each graft has its benefits and disadvantages for the individual patient, depending on age, skeletal maturity, and goals for recovery. Lateral extra-articular tenodesis (LET) is another option to consider with paediatric ACLR because LET has been shown to decrease the re-rupture rate in adult ACLR. After surgery, patient follow-up until at least the growth plates are closed is important. This article aims to provide an overview and comparison of the various graft types to aid in the graft choice decision making process for paediatric ACLR.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Patellar Ligament , Adult , Humans , Female , Child , Male , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/methods , Patellar Ligament/transplantation , Tendons/surgery , Transplantation, Autologous
2.
Genes (Basel) ; 13(12)2022 12 14.
Article in English | MEDLINE | ID: mdl-36553626

ABSTRACT

Joint laxity is a multifactorial phenotype with a heritable component. Mutations or common polymorphisms within the α1(V) (COL5A1), α1(XI) (COL11A1) and α2(XI) (COL11A2) collagen genes have been reported or proposed to associate with joint hypermobility, range of motion and/or genu recurvatum. The aim of this study was to investigate whether polymorphisms within these collagen-encoding genes are associated with measurements of knee joint laxity and computed ligament length changes within the non-dominant leg. One hundred and six healthy participants were assessed for genu recurvatum (knee hyperextension), anterior-posterior tibial translation, external-internal tibial rotation and ligament length changes during knee rotation of their non-dominant leg. Participants were genotyped for COL5A1 rs12722 (T/C), COL11A1 rs3753841 (C/T), COL11A1 rs1676486 (T/C) and COL11A2 rs1799907 (A/T). The genotype-genotype combination of any two or more of the four COL5A1 rs12722 CC, COL11A1 rs3753841 CC, COL11A1 rs1676486 TT and COL11A2 rs1799907 AA genotypes was associated with decreased active and passive knee hyperextension. These genotype-genotype combinations, including sex (male), increased age and decreased body mass collectively, also contributed to decreased passive knee hyperextension. These findings suggest that COL5A1, COL11A1 and COL11A2 gene-gene interactions are associated with knee hyperextension measurements of the non-dominant leg of healthy individuals.


Subject(s)
Collagen , Joint Instability , Knee Joint , Humans , Male , Collagen/genetics , Genotype , Joint Instability/genetics , Knee Joint/physiopathology , Polymorphism, Genetic
3.
Clin Biomech (Bristol, Avon) ; 100: 105822, 2022 12.
Article in English | MEDLINE | ID: mdl-36436321

ABSTRACT

BACKGROUND: Joint laxity is a multifactorial phenotype with a heritable component. Type I collagen gene (COL1A1) mutations cause connective tissue disorders with joint hypermobility as a clinical feature, while variants within COL1A1 and type III collagen gene (COL3A1) are associated with musculoskeletal injuries. The aim of this study was to investigate whether COL1A1 and COL3A1 variants are associated with measurements of non-dominant knee joint laxity and computed ligament length changes. METHODS: 106 moderately active uninjured participants were assessed for genu recurvatum, anterior-posterior tibial translation, external-internal tibial rotation and calculated ligament length changes during knee rotation. Participants were genotyped for COL1A1 rs1107946, rs1800012 and COL3A1 rs1800255. FINDINGS: The COL1A1 rs1107946 GG genotype had significantly larger external rotation [GG: 5.7° (4.9°;6.4°) vs GT: 4.6° (4.2°;5.5°), adjusted P = 0.014], internal rotation [GG: 5.9° (5.3°;6.6°) vs GT: 5.4° (4.7°;6.2°), adjusted P = 0.014], and slack [GG: 18.2° ± 3.2° vs GT: 16.1° ± 3.1°, adjusted P = 0.014]. The GG genotype at both COL1A1 variants had significantly larger active displacement [GG + GG: 6.0 mm (3.8 mm;8.0 mm) vs other genotype combinations: 4.0 mm (2.5 mm;6.0 mm), P < 0.001] and maximum displacement [GG + GG: 8.0 mm (6.9 mm;10.6 mm) vs other genotype combinations: 6.0 mm (5.0 mm;9.0 mm), P = 0.003]. COL1A1 rs1107946 significantly contributed to increased external and internal rotation in multilinear regression models, while both COL1A1 variants, significantly contributed to increased active displacement and slack. Larger medial and lateral cruciate ligament length changes were reported in participants with GG genotypes at both COL1A1 variants. INTERPRETATION: These findings suggest that the COL1A1 variants are associated with knee rotational laxity and changes in ligament length.


Subject(s)
Collagen Type I, alpha 1 Chain , Collagen Type III , Joint Instability , Ligaments, Articular , Humans , Collagen Type III/genetics , Joint Instability/genetics , Joint Instability/pathology , Collagen Type I, alpha 1 Chain/genetics , Ligaments, Articular/pathology , Genetic Variation
4.
J ISAKOS ; 7(6): 150-161, 2022 12.
Article in English | MEDLINE | ID: mdl-35998884

ABSTRACT

INTRODUCTION: Many factors can affect the return to pivoting sports, after an Anterior Cruciate Ligament Reconstruction. Prehabilitation, rehabilitation, surgical and psychological aspects play an essential role in the decision to return to sports. The purpose of this study is to reach an international consensus about the best conditions for returning to sports in soccer-one of the most demanding level I pivoting sports after anterior cruciate ligament (ACL) reconstruction. METHODS: 34 International experts in the management of ACL injuries, representing all the Continents were convened and participated in a process based on the Delphi method to achieve a consensus. 37 statements related to ACL reconstruction were reviewed by the experts in three rounds of surveys in complete anonymity. The statements were prepared by the working group based on previous literature or systematic reviews. Rating agreement through a Likert Scale: strongly agree, agree, neither agree or disagree, disagree and strongly disagree was used. To define consensus, it was established that the assertions should achieve a 75% of agreement or disagreement. RESULTS: Of the 37 statements, 10 achieved unanimous consensus, 18 non-unanimous consensus and 9 did not achieve consensus. In the preoperative, the correction of the range of motion deficit, the previous high level of participation in sports and a better knowledge of the injury by the patient and compliance to participate in Rehabilitation were the statements that reached unanimous consensus. During the surgery, the treatment of associated injuries, as well as the use of autografts, and the addition of a lateral extra-articular tenodesis in some particular cases (active young athletes, <25 years old, hyperlaxity, high rotatory laxity and revision cases) obtained also 100% consensus. In the postoperative period, psychological readiness and its validation with scales, adequate physical preparation, as well as not basing the RTSS purely on the time of evolution after surgery, were the factors that reached unanimous Consensus. CONCLUSIONS: The consensus statements derived from this international ISAKOS leaders, may assist clinicians in deciding when to return to sports soccer in patients after an ACL reconstruction. Those statements that reached 100% consensus have to be strongly considered in the final decision to RTS soccer.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Soccer , Sports , Humans , Adult , Soccer/injuries , Return to Sport/psychology , Anterior Cruciate Ligament Injuries/surgery
5.
J Exp Orthop ; 7(1): 79, 2020 Oct 07.
Article in English | MEDLINE | ID: mdl-33026544

ABSTRACT

PURPOSE: To evaluate clinical ad radiological outcomes of anterior cruciate ligament (ACL) reconstruction with an immunochemically modified porcine patellar tendon xenograft controlled against human Achilles tendon allograft at 24-month minimum follow-up. METHODS: 66 patients undergoing arthroscopic ACL reconstruction were randomized into 2 groups: 34 allografts and 32 xenografts treated to attenuate the host immune response. Follow-up was 24-month minimum. Anterior knee stability was measured as KT - 1000 side-to-side laxity difference (respect to the contralateral healthy knee). Functional performance was assessed by one-legged hop test. Objective manual pivot-shift test and subjective (IKDC, Tegner and SF-36) outcomes were collected. MRI and standard X-Ray were performed. RESULTS: 61 subjects (32 allograft, 29 xenograft) were evaluated at 12 and 24 months. Six of the subjects in xenograft group (20.6%) got an infection attributed to a water-based pathogen graft contamination in processing. Intention-to-treat analysis (using the last observation carried forward imputation method) revealed higher KT - 1000 laxity in xenograft group at 24-month follow-up (P = .042). Also pivot-shift was higher in xenograft group at 12-month (P = .015) and 24-month follow-up (P = .038). Per-protocol analysis (missing/contaminated subjects excluded) did not revealed clinical differences between groups. Tibial tunnel widening in the allograft group was low, whereas xenograft tunnel widening was within the expected range of 20-35% as reported in the literature. No immunological reactivity was associated to xenograft group. CONCLUSIONS: High infection rate (20.6%) was reported in xenograft group. Both groups of patients achieved comparable clinical outcomes if missing/contaminated subjects are excluded. Improved harvesting/processing treatments in future studies using xenografts for ACL reconstruction are needed to reduce infection rate, otherwise xenograft should not be used in ACL reconstruction. LEVEL OF EVIDENCE: Multicenter and double-blinded Randomized Controlled Clinical Trial, Level I.

6.
Article in English | MEDLINE | ID: mdl-31579106

ABSTRACT

The Atlas Knee System was designed to fill the gap between no longer effective conservative treatments and more invasive surgery for young patients with medial knee osteoarthritis (OA). This article reports on the 2-year results of a single-arm study of 26 subjects who previously reported favorable clinical outcomes 1 year post implantation. Western Ontario and McMaster Universities Osteoarthritis Index pain and function scores improved by a clinically meaningful amount relative to baseline, and subjects had a return to normal range of motion. This study confirmed that the benefit of a joint unloading device in the management of young patients with medial knee OA is maintained over 2 years. This trial was registered with ClinicalTrials.gov (NCT02711254).

7.
Knee Surg Sports Traumatol Arthrosc ; 27(10): 3318-3326, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30604253

ABSTRACT

PURPOSE: This study aimed at evaluating the association between the volume of the bone bruises and the magnitude of knee sagittal laxity and presence of meniscal injury in patients with anterior cruciate ligament (ACL) rupture. It was hypothesized that higher volumes of bone bruises will be associated with increased knee laxity and the presence of meniscal injury. METHODS: Patients with clinical diagnosis of ACL injury were referred for magnetic resonance imaging (MRI) and knee sagittal laxity measurement with a mechanical instrumented device (Porto-Knee Testing Device). The femoral and tibial bone bruises were assessed by MRI and the volume measured by manually contouring the bone bruise using a computerized software and computed by a mathematical algorithm combining all measured areas. The ACL rupture type (partial or total), meniscal tear (medial or lateral), and the localization of bone bruise were also analyzed. RESULTS: Seventy-six ACL-ruptured participants were included and 34 patients displayed bone bruises. Tibiofemoral sagittal laxity was higher in participants with complete ACL rupture (p < 0.05), but not influenced by the volume of bone bruises and meniscal status (n.s.). The volume of bone bruises was not significantly associated with the meniscal lesion or with the tibiofemoral sagittal laxity, independently of the meniscal injury status (n.s.). CONCLUSIONS: The volume of femoral and/or tibial bone bruises was not associated with the type of ACL injury, tibiofemoral sagittal laxity or the status of meniscal injury. Bone bruises must be considered as a radiographic sign of injury and should not be suggestive of injury severity and not overvalued. LEVEL OF EVIDENCE: Retrospective cohort study, Level III. IRB NUMBER: 0011/0014.


Subject(s)
Anterior Cruciate Ligament Injuries/pathology , Contusions/pathology , Femur/pathology , Joint Instability/pathology , Knee Joint/pathology , Tibia/pathology , Adult , Anterior Cruciate Ligament Injuries/complications , Cartilage, Articular/injuries , Contusions/complications , Female , Humans , Joint Instability/etiology , Magnetic Resonance Imaging/methods , Male , Middle Aged , Retrospective Studies , Young Adult
8.
Knee Surg Sports Traumatol Arthrosc ; 26(9): 2704-2715, 2018 Sep.
Article in English | MEDLINE | ID: mdl-28913600

ABSTRACT

PURPOSE: The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. METHODS: In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. RESULTS: A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. CONCLUSIONS: This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions. LEVEL OF EVIDENCE: I.


Subject(s)
Arthroplasty, Subchondral , Bone Diseases/surgery , Bone Regeneration , Cartilage Diseases/surgery , Knee Joint/surgery , Tissue Scaffolds , Adult , Biocompatible Materials , Biomimetic Materials , Bone Diseases/pathology , Cartilage Diseases/pathology , Cartilage, Articular/pathology , Cartilage, Articular/surgery , Collagen , Durapatite , Female , Humans , Knee Joint/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Nanostructures , Prospective Studies , Young Adult
9.
J Sports Sci ; 36(5): 551-557, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28502223

ABSTRACT

The angiogenesis-signalling pathway is a physiological response after mechanical loading to promote matrix remodelling and thereby maintain tissue homeostasis. Studies have shown increased expression of angiogenic molecules in response to loading and in ruptured ligaments. Recently, polymorphisms within the vascular endothelial growth factor A (VEGFA) and kinase insert-domain receptor (KDR) genes were associated with risk of anterior cruciate ligament (ACL) ruptures and Achilles tendinopathy in Caucasian study groups. A case-control genetic association study was conducted on 100 controls and 98 participants with surgically-diagnosed ACL ruptures; of which 51 participants reported non-contact mechanism of injury (NON). All participants were genotyped for five functional polymorphisms: VEGFA (rs699947, rs1570360, rs2010963) and KDR (rs2071559, rs1870377). Haplotypes were inferred. In the male participants, the KDR rs2071559 AG genotype was significantly over-represented (P = 0.048, OR: 1.90, 95% CI: 1.00-3.59) in the controls. Furthermore, the GG genotype was significantly under-represented in the male controls compared to the male ACL group (P = 0.018, OR: 2.77, 95% CI: 1.17-6.55) and the male NON subgroup (P = 0.013, OR: 3.26, 95% CI: 1.24-8.58). Haplotype analysis implicated the KDR gene in all participants and in male participants separately. Collectively, these results implicate the angiogenesis-signalling pathway as a potentially key biological pathway contributing to ACL injury susceptibility.


Subject(s)
Anterior Cruciate Ligament Injuries/genetics , Black People/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-2/genetics , Adult , Athletic Injuries/genetics , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Male , Polymorphism, Single Nucleotide , Risk Factors , Sex Factors , South Africa , Young Adult
10.
Article in English | MEDLINE | ID: mdl-28989290

ABSTRACT

In young patients with medial knee osteoarthritis (OA), surgical intervention may not be desirable due to preferences to avoid bone cutting procedures, return to high activity levels, and prolong implant survival. The Atlas Knee System was designed to fill the gap between ineffective conservative treatments and invasive surgery. This single-arm study included 26 patients, aged 25 to 65 years, who completed 12 months of follow-up. All dimensions of the Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Society Score significantly improved from baseline to 12 months. About 96.2% and 92.3% of patients experienced a ⩾20% improvement in their KOOS pain and WOMAC pain scores, respectively, at 12 months. This study highlights the potential benefit of a joint unloading device in the management of young patients with medial knee OA. The trial is still ongoing and another analysis is planned at 24 months.

11.
Clin Biomech (Bristol, Avon) ; 49: 78-84, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28892671

ABSTRACT

BACKGROUND: Biomechanical deviations long (approx. 5years) after anterior cruciate ligament reconstruction have not been quantified in males, despite their distinct risk profile as compared to females. These deviations can indicate altered joint loading during chronic, repetitive motions. METHODS: Cross-sectional study, comparing kinematic and kinetic variables between 15 male anterior cruciate ligament reconstructed patients and 15 healthy controls. During walking and running gait, measurements were taken of impact dynamics, knee and hip sagittal plane angles and moments, and knee varus angles and adduction moments. FINDINGS: Comparing affected limbs to control limbs, significantly lower maximum (P=0.001) and initial (P=0.003) loading rates were found during running, but not in walking. Hip angles were lower for affected limbs of patients compared to the control group (P=0.039) in walking, but not during running. Between-limb comparisons showed important differences in symmetry of the affected patients. Maximum force during running was higher in the unaffected limb (P=0.015), which was linked with a higher loading rate (P=0.008). Knee flexion angle was reduced by 2° on average for the affected limb during running (P=0.010), and both walking and running knee and hip moments showed differences. Knee varus angle showed a 1° difference during walking (P<0.001), but not during running. Knee adduction moment was significantly lower (more valgus) during both walking and running. INTERPRETATION: Male anterior cruciate ligament reconstructed patients demonstrate persistent, clinically important gait asymmetries and differences from healthy controls long after surgery in kinematics, kinetics, and impact biomechanics.


Subject(s)
Anterior Cruciate Ligament Injuries/physiopathology , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction , Gait/physiology , Adult , Biomechanical Phenomena , Cross-Sectional Studies , Humans , Knee Injuries/surgery , Knee Joint/physiology , Male , Surveys and Questionnaires , Walking/physiology
12.
J Sci Med Sport ; 20(2): 152-158, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27720349

ABSTRACT

OBJECTIVES: The extracellular matrix (ECM) of ligaments continuously undergoes remodelling in order to maintain tissue homeostasis. Several key mediators of ECM remodelling were chosen for investigation in the present study. It is thought that polymorphisms within genes encoding signalling molecules may contribute to inter-individual variation in the responses to mechanical loading, potentially altering risk of injury. DESIGN: A genetic association study was conducted on 232 asymptomatic controls (CON) and 234 participants with surgically diagnosed anterior cruciate ligament (ACL) ruptures; of which 135 participants reported a non-contact mechanism of injury (NON subgroup). METHODS: All participants were genotyped for ten variants in eight genes encoding ECM remodelling proteins. Haplotypes and allele combinations were also inferred. RESULTS: The CASP8 rs3834129 ins allele was significantly over-represented in the male CON group compared to the male NON subgroup (p=0.047, OR: 1.46, 95% CI: 1.01-2.12). In female participants, the IL1B rs16944 TT genotype was significantly under-represented in the CON group compared to the NON subgroup (p=0.039, OR: 3.06, 95% CI: 1.09-8.64). Haplotype analysis revealed an under-representation of the CASP8 rs3834129-rs1045485 del-G haplotype in the CON group compared to both the ACL group (p=0.042; haplo.score:2.03) and the NON subgroup (p=0.037; haplo.score:2.09). Furthermore, following a pathway-based approach, genetic variants involved in the cell signalling cascade were associated with ACL injury risk. CONCLUSIONS: The novel independent associations and allele combinations observed implicate the apoptosis and cell signalling cascades as potential contributors to ACL injury susceptibility. Furthermore, these genetic variants may potentially modulate ECM remodelling in response to loading and ultimately contribute to ligament capacity.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament/physiopathology , Extracellular Matrix/genetics , Polymorphism, Single Nucleotide , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Ligaments , Male , Risk Factors
14.
Eur J Sport Sci ; 15(4): 341-50, 2015.
Article in English | MEDLINE | ID: mdl-25073002

ABSTRACT

The COL5A1 and COL12A1 variants are independently associated with modulating the risk of anterior cruciate ligament (ACL) rupture in females. The objective of this study was to further investigate if COL3A1 and COL6A1 variants independently, as well as, collagen gene-gene interactions, modulate ACL rupture risk. Three hundred and thirty-three South African (SA, n = 242) and Polish (PL, n = 91) participants with diagnosed ACL ruptures and 378 controls (235 SA and 143 PL) were recruited. Participants were genotyped for COL3A1 rs1800255 G/A, COL5A1 rs12722 (T/C), COL6A1 rs35796750 (T/C) and COL12A1 rs970547 (A/G). No significant associations were identified between COL6A1 rs35796750 and COL3A1 rs1800255 genotypes and risk of ACL rupture in the SA cohort. The COL3A1 AA genotype was, however, significantly (p = 0.036) over-represented in the PL ACL group (9.9%, n = 9) when compared to the PL control (CON) group (2.8%, n = 4). Although there were genotype distribution differences between the SA and PL cohorts, the T+A-inferred pseudo-haplotype constructed from COL5A1 and COL12A1 was significantly over-represented in the female ACL group when compared to the female CON group within the SA (T+A ACL 50.5%, T+A CON 38.1%, p = 0.022), PL (T+A ACL 56.3%, T+A CON 36.3%, p = 0.029) and combined (T+A ACL 51.8%, T+A CON 37.5%, p = 0.004) cohorts. In conclusion, the novel main finding of this study was a significant interaction between the COL5A1 rs12722 T/C and COL12A1 rs970547 A/G variants and risk of ACL injury. These results highlight the importance of investigating gene-gene interactions in the aetiology of ACL ruptures in multiple independent cohorts.


Subject(s)
Anterior Cruciate Ligament Injuries , Collagen Type III/genetics , Collagen Type VI/genetics , Collagen Type V/genetics , Collagen Type XII/genetics , Adolescent , Adult , Case-Control Studies , Female , Gene Frequency , Genotype , Humans , Male , Poland , Polymorphism, Single Nucleotide , Rupture/genetics , Self Report , South Africa , White People/genetics , Young Adult
15.
J Orthop Res ; 32(12): 1612-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25111568

ABSTRACT

Angiogenesis-associated signaling is a fundamental component in the remodeling of the extracellular matrix in response to loading. Genes encoding protein components within this signaling cascade are therefore suitable candidates for investigation into ACL injury susceptibility: namely, vascular endothelial growth factor A isoform (VEGFA), kinase insert-domain receptor (KDR), nerve growth factor (NGF), and hypoxia inducible factor-1α (HIF1A). A case-control genetic association study was conducted on 227 asymptomatic control participants and 227 participants with surgically diagnosed ACL ruptures of which 126 participants reported a non-contact mechanism of rupture. All participants were genotyped for seven polymorphisms within the four genes. The VEGFA rs699947 CC genotype (p=0.010, OR: 1.92, 95% CI: 1.17-3.17) was significantly over-represented within participants with non-contact ACL ruptures. The VEGFA rs1570360 GA genotype was significantly over-represented in the CON group (p=0.007, OR: 1.70, 95% CI: 1.16-2.50). Furthermore, the KDR rs2071559 GA genotype was significantly over-represented in the female controls (p=0.023, OR: 2.16, 95% CI: 1.11-4.22). Inferred haplotype analyses also implicated genomic regions spanning the VEGFA and KDR genes. These novel findings suggest that regions within VEGFA and KDR may be implicated in the pathophysiology of ACL ruptures; highlighting the potential biological significance of angiogenesis-associated signaling in the aetiology of ACL ruptures.


Subject(s)
Anterior Cruciate Ligament Injuries , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-2/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genotype , Haplotypes , Humans , Male , Risk , Rupture , Signal Transduction
16.
Br J Sports Med ; 48(22): 1640-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24552666

ABSTRACT

BACKGROUND: Genetic variants within genes involved in fibrillogenesis have previously been implicated in anterior cruciate ligament (ACL) injury susceptibility. Proteoglycans also have important functions in fibrillogenesis and maintaining the structural integrity of ligaments. Genes encoding proteoglycans are plausible candidates to be investigated for associations with ACL injury susceptibility; polymorphisms within genes encoding the proteoglycans aggrecan (ACAN), biglycan (BGN), decorin (DCN), fibromodulin (FMOD) and lumican (LUM) were examined. METHODS: A case-control genetic association study was conducted. 227 participants with surgically diagnosed ACL ruptures (ACL group) and 234 controls without any history of ACL injury were genotyped for 10 polymorphisms in 5 proteoglycan genes. Inferred haplotypes were constructed for specific regions. RESULTS: The G allele of ACAN rs1516797 was significantly under-represented in the controls (p=0.024; OR=0.72; 95% CI 0.55 to 0.96) compared with the ACL group. For DCN rs516115, the GG genotype was significantly over-represented in female controls (p=0.015; OR=9.231; 95%CI 1.16 to 73.01) compared with the ACL group and the AA genotype was significantly under-represented in controls (p=0.013; OR=0.33; 95% CI 0.14 to 0.78) compared with the female non-contact ACL injury subgroup. Haplotype analyses implicated regions overlapping ACAN (rs2351491 C>T-rs1042631 T>C-rs1516797 T>G), BGN (rs1126499 C>T-rs1042103 G>A) and LUM-DCN (rs2268578 T>C-rs13312816 A>T-rs516115 A>G) in ACL injury susceptibility. CONCLUSIONS: These independent associations and haplotype analyses suggest that regions within ACAN, BGN, DCN and a region spanning LUM-DCN are associated with ACL injury susceptibility. Taking into account the functions of these genes, it is reasonable to propose that genetic sequence variability within the genes encoding proteoglycans may potentially modulate the ligament fibril properties.


Subject(s)
Aggrecans/genetics , Anterior Cruciate Ligament Injuries , Biglycan/genetics , Chondroitin Sulfate Proteoglycans/genetics , Decorin/genetics , Extracellular Matrix Proteins/genetics , Keratan Sulfate/genetics , Proteoglycans/genetics , Adult , Case-Control Studies , Female , Fibrillar Collagens/genetics , Fibromodulin , Genetic Predisposition to Disease/genetics , Genotype , Haplotypes , Humans , Lumican , Male , Polymorphism, Single Nucleotide/genetics , Risk Factors , Rupture/genetics
17.
Knee Surg Sports Traumatol Arthrosc ; 20(4): 793-800, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22207028

ABSTRACT

UNLABELLED: The goal of anterior cruciate ligament (ACL) reconstruction surgery is to eliminate the pivot shift phenomenon. Different injury mechanisms and injury patterns may lead to specific knee laxity patterns. Computer navigation is helpful for the surgeon during examination under anesthesia. Surgical treatment may have to be altered if high-grade laxity is detected preoperatively for example by utilizing a computer navigation that is a helpful adjunct for surgeons during examination under anesthesia. A typical case for revision ACL reconstruction is presented. This article describes several techniques of laxity assessments. Based on the type and degree of pathologic laxity, a treatment algorithm has been developed. LEVEL OF EVIDENCE: V.


Subject(s)
Algorithms , Anterior Cruciate Ligament Reconstruction/adverse effects , Anterior Cruciate Ligament/surgery , Arthrometry, Articular , Joint Instability/surgery , Surgery, Computer-Assisted/methods , Adolescent , Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction/methods , Biomechanical Phenomena , Follow-Up Studies , Football/injuries , Humans , Joint Instability/diagnosis , Knee Injuries/diagnosis , Knee Injuries/surgery , Male , Postoperative Complications/diagnosis , Postoperative Complications/surgery , Range of Motion, Articular/physiology , Reoperation/methods , Risk Assessment , Tenodesis/methods , Treatment Outcome
18.
Am J Sports Med ; 39(1): 48-56, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20956265

ABSTRACT

BACKGROUND: While single-bundle anterior cruciate ligament reconstruction reduces anterior-posterior laxity, studies have demonstrated residual rotational instability. Improved pivot-shift results have been shown with the double-bundle graft; however, no study has compared rotational laxity outcome of these surgical techniques in vivo under quantified, isolated torsional loading. HYPOTHESIS: The anterior cruciate ligament-deficient knee exhibits greater rotational laxity than the contralateral uninjured knee. The double-bundle reconstruction restores rotational joint stability to a greater extent than single-bundle surgery. STUDY DESIGN: Controlled laboratory study. METHODS: Rotational laxity of 32 patients with unilateral anterior cruciate ligament injury was assessed in both knees at full extension and 30° of flexion using a magnetic resonance imaging-compatible torsional loading device. Patients were randomly allocated either a single- or double-bundle reconstruction and reassessed 5 months after surgery. RESULTS: The anterior cruciate ligament-deficient knees demonstrated greater laxity to internal rotational torque in the extended position, but not in the 30° flexed position. No significant differences in rotational laxity were found between single- and double-bundle reconstructions. In extension, excessive internal rotational laxity of injured compared with contralateral knees was reduced by anterior cruciate ligament reconstruction. The single-bundle reconstruction did not affect internal rotation compared with contralateral or preoperative groups. In response to internal rotational torque in the flexed knee position, the double-bundle reconstruction reduced laxity to 10.8° from the pre-operative value of 15.3° (P = .058); postoperative rotation was also significantly less than the contralateral laxity of 16.4° (P = .022). CONCLUSION: The ruptured anterior cruciate ligament resulted in increased internal rotational laxity only in the extended position. The single-bundle reconstruction did not affect rotational restraint compared with contralateral or preoperative groups. The double-bundle procedure significantly reduced internal laxity in the flexed position when compared with normal. CLINICAL RELEVANCE: As the anterior cruciate ligament is not the primary restraint to rotation, its contribution to joint stability is limited under isolated torsional load. While the double-bundle graft demonstrates superior rotational constraint, this may be excessive for isolated anterior cruciate ligament rupture.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament/surgery , Joint Instability/surgery , Orthopedic Procedures/methods , Adult , Female , Femur/surgery , Humans , Male , Middle Aged , Rotation , Rupture/surgery , Tibia/surgery , Treatment Outcome , Young Adult
19.
Br J Sports Med ; 44(16): 1160-5, 2010 Dec.
Article in English | MEDLINE | ID: mdl-19443461

ABSTRACT

BACKGROUND: Anterior cruciate ligament (ACL) ruptures are among the most severe musculoskeletal soft tissue injuries. However, the exact mechanisms which cause these acute injuries are unknown. Recently, sequence variants within two genes, namely COL1A1 and COL5A1, which code for the α1 chains of types I and V collagen respectively, were shown to be associated with ACL ruptures. Type XII collagen, similarly to types I and V collagen, is a structural component of the ligament fibril and is encoded by a single gene, COL12A1. OBJECTIVE: The aim of this study was to investigate whether sequence variants within COL12A1 are associated with ACL ruptures. METHODS: One hundred and twenty-nine (38 female) participants with clinically and surgically diagnosed ACL ruptures, as well as 216 (83 female) physically active controls participants (CON) without any history of ACL injury were included in this case-control genetic association study. All participants were genotyped for the AluI and BsrI restriction fragment length polymorphisms (RFLPs) within COL12A1. RESULTS: The AA genotype of the COL12A1 AluI RFLP was significantly over-represented in the female (OR=2.4, 95% CI 1.0 to 5.5, p=0.048), but not male (p=0.359) ACL participants. There were no genotype differences between the ACL and CON group for the BsrI RFLP. CONCLUSION: The COL12A1 AluI RFLP is associated with ACL ruptures among female participants in this study. The results suggest that females with an AA genotype are at increased risk of ACL ruptures. These initial genetic association studies should be explored further and, if repeated, incorporated into multifactorial models developed to identify predisposed individuals.


Subject(s)
Anterior Cruciate Ligament Injuries , Collagen Type XII/genetics , Polymorphism, Restriction Fragment Length/genetics , Adult , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Male , Pedigree , Rupture/genetics , Sex Characteristics
20.
Am J Sports Med ; 37(11): 2234-40, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19654427

ABSTRACT

BACKGROUND: Anterior cruciate ligament ruptures, especially to young female athletes, are a cause of major concern in the sports medicine fraternity. The major structural constituents of ligaments are collagens, specifically types I and V. Recently, the gene that encodes for the alpha1 chain of type I collagen (COL1A1) has been shown to be associated with an increased risk of cruciate ligament ruptures. The COL5A1 gene, which encodes for the alpha1 chain of type V collagen, has been shown to be associated with Achilles tendon injuries. PURPOSE: The study was conducted to determine (1) if 2 sequence variants (BstUI and DpnII restriction fragment length polymorphisms [RFLPs]) within the COL5A1 gene are associated with an increased risk of anterior cruciate ligament ruptures, and (2) if there were any gender-specific positive associations between the 2 COL5A1 sequence variants and risk of anterior cruciate ligament ruptures. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: A total of 129 white participants (38 women) with surgically diagnosed anterior cruciate ligament ruptures and 216 physically active control participants (84 women) without any history of ACL injury were included in this case-control genetic association study. All participants were genotyped for the COL5A1 BstUI and DpnII RFLPs. RESULTS: There was a significant difference in the BstUI RFLP genotype frequency between the anterior cruciate ligament rupture and physically active control groups among the female participants, but not the male participants. The CC genotype in the female participants was significantly underrepresented in the anterior cruciate ligament rupture group compared with the controls (27.4% vs 5.6%; odds ratio = 6.6; 95% confidence interval, 1.5-29.7; P = .006). There were no differences in the DpnII RFLP genotype distributions between the anterior cruciate ligament rupture and physically active control groups. CONCLUSION: The CC genotype of the COL5A1 BstUI RFLP was underrepresented in female participants with anterior cruciate ligament ruptures. CLINICAL RELEVANCE: This is the first study to show that there is a specific genetic risk factor associated with risk of anterior cruciate ligament ruptures in female athletes.


Subject(s)
Anterior Cruciate Ligament Injuries , Collagen Type V/genetics , Knee Injuries/genetics , Adolescent , Adult , Case-Control Studies , Female , Gene Frequency , Genotype , Humans , Male , Polymorphism, Restriction Fragment Length , Risk Factors , Rupture/genetics , Sex Characteristics , Young Adult
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