Coxa valga and antetorta increases differences among different femoral version measurements : potential implications for derotational femoral osteotomy planning.

AIMS To evaluate how abnormal proximal femoral anatomy affects different femoral version measurements in young patients with hip pain. METHODS First, femoral version was measured in 50 hips of symptomatic consecutively selected patients with hip pain (mean age 20 years (SD 6), 60% (n = 25) females) on preoperative CT scans using different measurement methods: Lee et al, Reikerås et al, Tomczak et al, and Murphy et al. Neck-shaft angle (NSA) and α angle were measured on coronal and radial CT images. Second, CT scans from three patients with femoral retroversion, normal femoral version, and anteversion were used to create 3D femur models, which were manipulated to generate models with different NSAs and different cam lesions, resulting in eight models per patient. Femoral version measurements were repeated on manipulated femora. RESULTS Comparing the different measurement methods for femoral version resulted in a maximum mean difference of 18° (95% CI 16 to 20) between the most proximal (Lee et al) and most distal (Murphy et al) methods. Higher differences in proximal and distal femoral version measurement techniques were seen in femora with greater femoral version (r > 0.46; p 0.37; p = 0.008) between all measurement methods. In the parametric 3D manipulation analysis, differences in femoral version increased 11° and 9° in patients with high and normal femoral version, respectively, with increasing NSA (110° to 150°). CONCLUSION Measurement of femoral version angles differ depending on the method used to almost 20°, which is in the range of the aimed surgical correction in derotational femoral osteotomy and thus can be considered clinically relevant. Differences between proximal and distal measurement methods further increase by increasing femoral version and NSA. Measurement methods that take the entire proximal femur into account by using distal landmarks may produce more sensitive measurements of these differences.Cite this article: Bone Jt Open 2022;3(10):759-766

Limited Hip Flexion and Internal Rotation Resulting From Early Hip Impingement Conflict on Anterior Metaphysis of Patients With Untreated Severe SCFE Using 3D Modelling.

INTRODUCTION Slipped capital femoral epiphysis (SCFE) is the most common hip disorder in adolescent patients that can result in complex 3 dimensional (3D)-deformity and hip preservation surgery (eg, in situ pinning or proximal femoral osteotomy) is often performed. But there is little information about location of impingement.Purpose/Questions: The purpose of this study was to evaluate (1) impingement-free hip flexion and internal rotation (IR), (2) frequency of impingement in early flexion (30 to 60 degrees), and (3) location of acetabular and femoral impingement in IR in 90 degrees of flexion (IRF-90 degrees) and in maximal flexion for patients with untreated severe SCFE using preoperative 3D-computed tomography (CT) for impingement simulation. METHODS A retrospective study involving 3D-CT scans of 18 patients (21 hips) with untreated severe SCFE (slip angle>60 degrees) was performed. Preoperative CT scans were used for bone segmentation of preoperative patient-specific 3D models. Three patients (15%) had bilateral SCFE. Mean age was 13±2 (10 to 16) years and 67% were male patients (86% unstable slip, 81% chronic slip). The contralateral hips of 15 patients with unilateral SCFE were evaluated (control group). Validated software was used for 3D impingement simulation (equidistant method). RESULTS (1) Impingement-free flexion (46±32 degrees) and IRF-90 degrees (-17±18 degrees) were significantly (P<0.001) decreased in untreated severe SCFE patients compared with contralateral side (122±9 and 36±11 degrees).(2) Frequency of impingement was significantly (P<0.001) higher in 30 and 60 degrees flexion (48% and 71%) of patients with severe SCFE compared with control group (0%).(3) Acetabular impingement conflict was located anterior-superior (SCFE patients), mostly 12 o'clock (50%) in IRF-90 degrees (70% on 2 o'clock for maximal flexion). Femoral impingement was located on anterior-superior to anterior-inferior femoral metaphysis (between 2 and 6 o'clock, 40% on 3 o'clock and 40% on 5 o'clock) in IRF-90 degrees and on anterior metaphysis (40% on 3 o'clock) in maximal flexion and frequency was significantly (P<0.001) different compared with control group. CONCLUSION Severe SCFE patients have limited hip flexion and IR due to early hip impingement using patient-specific preoperative 3D models. Because of the large variety of hip motion, individual evaluation is recommended to plan the osseous correction for severe SCFE patients. LEVEL OF EVIDENCE Level III

Validation of Porcine Knee as a Sex-specific Model to Study Human Anterior Cruciate Ligament Disorders

Abstract Background Animal models have long been considered an important modality for studying ACL injuries. However, to our knowledge, the value of these preclinical models to study sex-related phenomena associated with ACL injury and recovery has not been evaluated. Questions/purposes We asked whether (1) prominent anatomic and (2) biomechanical factors differ between female and male porcine knees, particularly those known to increase the risk of ACL injury. Methods Eighteen intact minipig knees (nine males, nine females) underwent MRI to determine the femoral bicondylar width, intercondylar notch size (width, area and index), medial and lateral tibial slope, ACL size (length, cross-sectional area, and volume), and medial compartment tibiofemoral cartilage thickness. AP knee laxity at 30°, 60°, and 90°flexion and ACL tensile structural properties were measured using custom-designed loading fixtures in a universal tensile testing apparatus. Comparisons between males and females were performed for all anatomic and biomechanical measures. The findings then were compared with published data from human knees. Results Female pigs had smaller bicondylar widths (2.9 mm, ratio = 0.93, effect size = À1.5) and intercondylar notches (width: 2.0 mm, ratio = 0.79, effect size = À2.8; area: 30.8 mm 2 , ratio = 0.76, effect size = 2.1; index: 0.4, ratio = 0.84, effect size = À2.0), steeper lateral tibial slope (4.3°, ratio = 1.13, effect size = 1.1), smaller ACL (length: 2.7 mm, ratio = 0.91, effect size = 1.1; area: 6.8 mm 2 , ratio = 0.74, effect size = À1.5; volume: 266.2 mm 3 , ratio = 0.68, effect size = À1.5), thinner medial femoral cartilage (0.4 mm, ratio = 0.8, effect size = À1.1), lower ACL yield load (275 N, ratio = 0.81, effect size = À1.1), and greater AP knee laxity at 30°( 0.7 mm, ratio = 1.32, effect size = 1.1) and 90°(0.5 mm, ratio = 1.24, effect size =

Structural and Anatomic Restoration of the Anterior Cruciate Ligament Is Associated With Less Cartilage Damage 1 Year After Surgery: Healing Ligament Properties Affect Cartilage Damage

Background: Abnormal joint motion has been linked to joint arthrosis after anterior cruciate ligament (ACL) reconstruction. However, the relationships between the graft properties (ie, structural and anatomic) and extent of posttraumatic osteoarthritis are not well defined. Hypotheses: (1) The structural (tensile) and anatomic (area and alignment) properties of the reconstructed graft or repaired ACL correlate with the total cartilage lesion area 1 year after ACL surgery, and (2) side-to-side differences in anterior-posterior (AP) knee laxity correlate with the total cartilage lesion area 1 year postoperatively. Study Design: Controlled laboratory study. Methods: Sixteen minipigs underwent unilateral ACL transection and were randomly treated with ACL reconstruction or bridge-enhanced ACL repair. The tensile properties, cross-sectional area, and multiplanar alignment of the healing ACL or graft, AP knee laxity, and cartilage lesion areas were assessed 1 year after surgery. Results: In the reconstructed group, the normalized graft yield and maximum failure loads, cross-sectional area, sagittal and coronal elevation angles, and side-to-side differences in AP knee laxity at 60° of flexion were associated with the total cartilage lesion area 1 year after surgery (R 2 > 0.5, P 0.5, P < .05). Smaller cartilage lesion areas were observed in the surgically treated knees when the structural and anatomic properties of the ligament or graft and AP laxity values were closer to those of the contralateral ACL-intact knee. Reconstructed grafts had a significantly larger normalized cross-sectional area and sagittal elevation angle (more vertical) when compared with repaired ACLs (P < .02). Conclusion: The tensile properties, cross-sectional area, and multiplanar alignment of the healing ACLs or grafts and AP knee laxity in reconstructed knees were associated with the extent of tibiofemoral cartilage damage after ACL surgery. Clinical Relevance: These data highlight the need for novel ACL injury treatments that can restore the structural and anatomic properties of the torn ACL to those of the native ACL in an effort to minimize the risk of early-onset posttraumatic osteoarthritis

The role of Gdf5 regulatory regions in development of hip morphology.

Given GDF5 involvement in hip development, and osteoarthritis (OA) and developmental hip dysplasia (DDH) risk, here we sought to assess the role(s) of GDF5 and its regulatory sequence on the development of hip morphology linked to injury risk. The brachypodism (bp) mouse, which harbors a Gdf5 inactivating mutation, was used to survey how Gdf5 loss of function impacts the development of hip morphology. Two transgenic Gdf5 reporter BAC lines were used to assess the spatiotemporal expression of Gdf5 regulatory sequences. Each BAC line was also used to assess the functional roles of upstream and downstream sequence on hip morphology. bp/bp mice had shorter femora with smaller femoral heads and necks as well as larger alpha angles, smaller anterior offsets, and smaller acetabula, compared to bp/+ mice (p<0.04). Regulatory sequences downstream of Gdf5 drove strong prenatal (E17) expression and low postnatal (6 months) expression across regions of femoral head and acetabulum. Conversely, upstream regulatory sequences drove very low expression at E17 and no detectable expression at 6 months. Importantly, downstream, but not upstream Gdf5 regulatory sequences fully restored all the key morphologic features disrupted in bp/bp mice. Hip morphology is profoundly affected by Gdf5 absence, and downstream regulatory sequences mediate its effects by controlling Gdf5 expression during development. This downstream region contains numerous enhancers harboring risk variants related to hip OA, DDH, and dislocation. We posit that subtle alterations to morphology driven by changes in downstream regulatory sequence underlie this locus' role in hip injury risk

Synovial fluid proteome changes in ACL injury-induced posttraumatic osteoarthritis: Proteomics analysis of porcine knee synovial fluid.

Surgical transection of the anterior cruciate ligament (ACL) in the porcine model leads to posttraumatic osteoarthritis if left untreated. However, a recently developed surgical treatment, bridge-enhanced ACL repair, prevents further cartilage damage. Since the synovial fluid bathes all the intrinsic structures of knee, we reasoned that a comparative analysis of synovial fluid protein contents could help to better understand the observed chondroprotective effects of the bridge-enhanced ACL repair. We hypothesized that post-surgical changes in the synovial fluid proteome would be different in the untreated and repaired knees, and those changes would correlate with the degree of cartilage damage. Thirty adolescent Yucatan mini-pigs underwent unilateral ACL transection and were randomly assigned to either no further treatment (ACLT, n = 14) or bridge-enhanced ACL repair (BEAR, n = 16). We used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. A linear mixed effect model was used to compare the normalized protein abundance levels between the groups at each time point. Bivariate linear regression analyses were used to assess the correlations between the macroscopic cartilage damage (total lesion area) and normalized abundance levels of each of the identified secreted proteins. There were no significant differences in cartilage lesion area or quantitative abundance levels of the secreted proteins between the ACLT and BEAR groups at 6 months. However, by 12 months, greater cartilage damage was seen in the ACLT group compared to the BEAR group (p = 0.005). This damage was accompanied by differences in the abundance levels of secreted proteins, with higher levels of Vitamin K-dependent protein C (p = 0.001), and lower levels of Apolipoprotein A4 (p = 0.021) and Cartilage intermediate layer protein 1 (p = 0.049) in the ACLT group compared to the BEAR group. There were also group differences in the secreted proteins that significantly changed in abundance between 6 and 12 months in ACLT and BEAR knees. Increased concentration of Ig lambda-1 chain C regions and decreased concentration of Hemopexin, Clusterin, Coagulation factor 12 and Cartilage intermediate layer protein 1 were associated with greater cartilage lesion area. In general, ACLT knees had higher concentrations of pro-inflammatory proteins and lower concentrations of anti-inflammatory proteins than BEAR group. In addition, the ACLT group had a lower and declining synovial concentrations of CILP, in contrast to a consistently high abundance of CILP in repaired knees. These differences suggest that the knees treated with bridge-enhanced ACL repair may be maintaining an environment that is more protective of the extracellular matrix, a function which is not seen in the ACLT knees

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

Abstract Background: Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer’s disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation. Methods: In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Results: Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA. Conclusion: There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid. The Translational potential of this article: There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA