Femoroacetabular Impingement Group Research Articles

Femurs in patients with hip dysplasia have fundamental shape differences compared with cam femoroacetabular impingement

ABSTRACT Femoral deformities are common in developmental dysplasia of the hip (DDH), but decisions about how to treat them are not standardized. Of interest are deformities that may be akin to cam femoroacetabular impingement (FAI). We used three-dimensional and two-dimensional measures to clarify the similarities and differences in proximal femur shape variation among female patients with DDH (n = 68) or cam FAI (n = 60). Three-dimensional measures included femoral head asphericity, as well as shape variation using statistical shape modeling and principal component analysis (PCA). Two-dimensional measures included the α-angle, head–neck offset (HNO) and the neck–shaft angle (NSA). Significant shape variations were captured in the first five PCA modes, with the greatest shared variation between groups being the length from the lesser trochanter to the femoral head and greater trochanter height. Variations unique to DDH were irregularities at different areas of the femoral head, but not at the lateral femoral head–neck junction where variation was strong in FAI. The FAI group also had unique variations in greater trochanter shape. DDH femoral heads were less spherical, as indicated by larger sphere-fitting errors (P < 0.001). Radiographically, the DDH group had significantly smaller α-angles (P < 0.001), larger head–neck offsets (P = 0.02) and larger NSAs (P < 0.001). Both the articular and extra-articular regions of the proximal femur have distinct shape features in DDH and cam FAI that can uniquely affect the biomechanics of each disorder. Accordingly, approaches to addressing each disorder should be unique.

Hip and Pelvis Movement Patterns in Patients With Femoroacetabular Impingement Syndrome Differ From Controls and Change After Hip Arthroscopy During a Step-Down Pivot-Turn Task

Background: Alterations in hip kinematics during functional tasks occur in positions that cause anterior impingement in patients with femoroacetabular impingement (FAI) syndrome. However, tasks that do not promote motions of symptomatic hip impingement remain understudied. Purpose: To compare movement patterns of the hip and pelvis during a step-down pivot-turn task between patients with FAI and controls as well as in patients with FAI before and after hip arthroscopy. Study Design: Controlled laboratory study. Methods: Three-dimensional motion capture was acquired in 32 patients with FAI and 27 controls during a step-down pivot-turn task. An FAI subsample (n = 14) completed testing 9.2 ± 2.0 months (mean ± SD; range, 5.8-13.1 months) after hip arthroscopy. Statistical parametric mapping analysis was used to analyze hip and pelvis time series waveforms (1) between the FAI and control groups, (2) in the FAI group before versus after hip arthroscopy, and (3) in the FAI group after hip arthroscopy versus the control group. Continuous parametric variables were analyzed by paired t test and nonparametric variables by chi-square test. Results: There were no significant differences in demographics between the FAI and control groups. Before hip arthroscopy, patients with FAI demonstrated reduced hip flexion ( P = .041) and external rotation ( P = .027), as well as decreased anterior pelvic tilt ( P = .049) and forward rotation ( P = .043), when compared with controls. After hip arthroscopy, patients demonstrated greater hip flexion ( P < .001) and external rotation of the operative hip ( P < .001), in addition to increased anterior pelvic tilt ( P≤ .036) and pelvic rise ( P≤ .049), as compared with preoperative values. Postoperatively, the FAI group demonstrated greater hip flexion ( P≤ .047) and lower forward pelvic rotation ( P = .003) as compared with the control group. Conclusion: Movement pattern differences between the FAI and control groups during the nonimpingement-related step-down pivot-turn task were characterized by differences in the sagittal and transverse planes of the hip and pelvis. After hip arthroscopy, patients exhibited greater hip flexion and external rotation and increased pelvic anterior tilt and pelvic rise as compared with presurgery. When compared with controls, patients with FAI demonstrated greater hip flexion and lower pelvic forward rotation postoperatively. Clinical Relevance: These findings indicate that hip and pelvis biomechanics are altered even during tasks that do not reproduce the anterior impingement position.

Differences in Kinematic Changes From Self-Selected to Fast Speed Gait in Asymptomatic Adults With Radiological Signs of Femoro-Acetabular Impingement.

Femoro-acetabular impingement (FAI) may present as alterations in the skeletal morphology of the hip. Repercussions of FAI can be witnessed in self-selected speed walking as well as physical exercise such as running or fast speed walking. The aim of this study was to investigate changes in kinematics at different gait speeds in subjects presenting with radiological findings invoking FAI. One hundred thirty asymptomatic adults underwent biplanar X-rays with a calculation of 3D hip parameters: acetabular anteversion, abduction and tilt, vertical center edge angle (VCE), femoral anteversion, neck-shaft angle, acetabular coverage of the femoral head, femoral head diameter and neck length. Parameters were classified according to FAI clinical thresholds. Two groups were created: Control group (63 subjects having up to one subnormal hip parameter in favour of FAI) and Radiographic FAI group (67 subjects having ≥2 subnormal hip parameters that might cause FAI). All subjects underwent 3D gait analysis at self-selected and fast speed, from which kinematic parameters were generated. Arithmetic differences between fast and self-selected speed gait were considered as gait changes. Subjects in the Radiographic FAI group had decreased acetabular tilt (24 vs. 19˚), anteversion (19 vs. 16˚), abduction (55 vs. 53˚), femoral anteversion (18 vs. 14˚) and increased VCE (29 vs. 33˚, all p<0.05), compared to controls.Changes from self-selected to fast speed showed that subjects in the Radiographic FAI group had lower range of motion (ROM) pelvic rotation (7 vs. 4˚) and ROM hip flexion/extension (10 vs. 7˚), reduced hip extension (-4 vs. -2˚) and step length (16 vs. 13 cm; all p<0.05). The Radiographic FAI group had decreased acetabular abduction, anteversion and femoral anteversion in favour of FAI. When adapting from self-selected to fast speed gait, the Radiographic FAI group seemed to limit pelvic rotation and hip flexion/extension resulting in a decrease in step length. These kinematic limitations were previously reported in subjects with symptomatic FAI. Gait analysis could be considered as a functional diagnostic tool to assess FAI along with radiological assessment.

Poster 112: Epigenetic Dysregulation during the OA Progression in Hip FAI

Objectives: Femoroacetabular impingement (FAI) is considered a leading cause of early hip OA, but initial molecular mechanisms that lead FAI patients to OA progression remains to be elucidated. Recent articles revealed that epigenetic changes are associated with OA progression, specifically, DNA methyltransferase 3B (DNMT3B) plays a critical role on cartilage homeostasis by attenuating catabolic gene expression. This study aimed to examine the catabolic state of articular chondrocyte (ACs) during OA progression in hip FAI disease, particularly the expressions of DNMT3B and 4-aminobutyrate aminotransferase (ABAT, downstream of DNMT3B), to assess how epigenetic dysregulation contributes to OA progression. Methods: Full-thickness cartilage samples were collected from the impingement zone. In total, twelve patients underwent hip preservation surgery for cam FAI (early-FAI) and twelve patients underwent total hip replacement for advanced OA secondary to cam FAI (late FAI-OA) were included in this study. As a non-disease (ND) group, five healthy samples were procured from hip joint cadavers. The explants were cultured in unstimulated conditions or catabolic stimulus (IL1β). Histological analyses was performed with safranin-O/fast-green. Gene expression was analyzed via qPCR for GAPDH, DNMT3B, ABAT, MMP-13, and COL10A1. Protein expression was analyzed by western blotting analysis for DNMT3B and ABAT. Methylation specific PCR was performed to assess the methylation status at ABAT promoter (epigenetic change). Results: The early FAI group included younger subjects with lower Tönnis grade than the late FAI OA group; however, there were no significant differences in gender, BMI, and α-angle between groups. Cartilage samples in early-FAI and late FAI-OA showed a histological OA phenotype (Figure 1A). RT-PCR confirmed increased expression of MMP-13 and COL10A1 in early and late FAI-OA (Figure 1B), confirming cartilage degeneration, catabolism, and chondrocyte hypertrophy when compared to ND group. Interestingly, RT-PCR revealed that expression of DNMT3B gradually declined as the disease progressed (ND vs early p&lt;0.001, early vs late p=0.016), while ABAT increased as the disease progressed (ND vs early p&lt;0.001, early vs late p=0.035, Figure 1B). IF staining confirmed that DNMT3B was abundantly expressed in chondrocytes of normal cartilage but the expression gradually decreased with disease progression, contrary ABAT expression gradually increased as the disease progressed (Figure 1C). These results were supported by protein expression in western blotting analysis (Figure 1D). In MSP analysis, the human ABAT promoter is characterized by a typical CpG island (Figure 2A, blue area). Additionally, there was hypomethylation at the ABAT promoter during end stage of disease (ND vs early p=0.022, early vs late p=0.042) (Figure 2B). Catabolic stimulus with IL1β for early FAI and late FAI-OA, accentuated the ABAT promoter hypomethylation (early FAI: nontreatment vs IL1β p=0.056, late FAI-OA: nontreatment vs IL1β p=0.015, Figure 2C) and resulted in further overexpression of ABAT and catabolic markers and decreased expression of DNMT3B (Figure 3A-C). These findings are supported by protein expression in western-blotting analysis (Figure 3D). Conclusions: In the present study, histological findings were similar in early and late FAI, but DNMT3B expression levels gradually decreased with OA progression, while ABAT and catabolic marker expression levels increased, suggesting a less catabolic phenotype in the early stage of disease. MSP analysis confirmed ABAT promoter hypo-methylation (epigenetically dysregulation) as hip OA progresses. Notably, in the current study, the inflammatory stimulus with IL1β further reduced DNA methylation at the ABAT promoter and resulted in a concomitant excessive increase of ABAT and catabolic markers in human hip OA ACs. This study suggests, for the first time, that cartilage degeneration in the impingement zone in hip FAI is progressive at the molecular level and may be controlled in part by an epigenetic dysregulation. Understanding the mechanism of OA disease in hip FAI will potentially provide concomitant interventional treatment to hip pre-OA disease.

Poster 113: Epigenetic Regulation of PPARγ Rescues Articular Chondrocytes from Catabolic State Suggesting PPARγ as a Potential Target to Slow Down Progression of OA in Hip FAI

Objectives: Hip Femoroacetabular impingement (FAI) has a high prevalence of chondral lesions, and the severity of chondral damage is associated with an increased risk of postoperative OA progression, but the mechanisms of cartilage degeneration in OA progression remains unclear. Peroxisome proliferator- activated receptor-gamma (PPARγ) is widely expressed in healthy articular chondrocytes (ACs) and plays an essential role in cartilage homeostasis. Recent investigations into OA pathogenesis have revealed that hyper or hypomethylation (by DNMTs) of OA susceptibility genes are involved in OA progression, especially downregulation of PPARγ has been linked to OA progression. This study aimed to investigate the expression of PPARγ and DNA methyltransferases enzymes (DNMT1 and DNMT3A) during progression of hip disease and 2) methylation changes in the PPARγ promoter area during progression of hip disease. Methods: Full-thickness cartilage samples were collected from the impingement zone. Twelve patients underwent hip preservation surgery for cam FAI (early FAI) and twelve patients underwent total hip replacement for advanced OA secondary to cam FAI (late FAI-OA) were included. As a non-disease (ND) group, six healthy samples were procured from hip joint cadavers. Cartilage explants were cultured in unstimulated conditions or catabolic stimulus (IL1β) with or without DNA demethylating agent 5-Aza-2’- deoxycytidine (5Aza). Histological analysis was performed with safranin O/fast green. Gene expression was analyzed via qPCR for GAPDH, DNMT1, DNMT3A, PPARγ, MMP13, and COL10A1. Methylation specific PCR (MSP) was performed to assess the methylation status at PPARγ promoter site. Chromatin immunoprecipitation (ChIP) assay was performed to confirm an interaction between DNMT3A and the PPAR promoter region. Results: The early FAI group included younger subjects than the late FAI OA group. Cartilage samples in early and late FAI-OA displayed a histological OA phenotype (Figure 1A). ACs in early and late FAI-OA displayed increased expression of catabolism and chondrocyte hypertrophy markers ( MMP13: ND vs early p&lt;0.001, ND vs late p&lt;0.001, COL10A1: ND vs early p&lt;0.001, ND vs late p&lt;0.001, Figure. 1B). Contrary, expression of PPARγ gradually declined as the disease progressed (ND vs early p=0.001, early vs late p=0.003, Figure. 1B). IF analysis also displayed a gradual decrease of the PPARγ expression during disease progression (ND vs early p=0.001, early vs late p=0.041, Figure 1C). In the assessment of the epigenetic mechanisms of aberrant DNA methylation in OA progression, overexpression of DNMT1 and DNMT3A levels was observed with disease progression in RT-PCR ( DNMT1: ND vs early p&lt;0.001, early vs late p=0.041, DNMT3A: ND vs early p=0.015, early vs late p=0.053,Figure 2A) and IF analysis ( DNMT1: ND vs early p&lt;0.001, early vs late p&lt;0.001, DNMT3A: ND vs early &lt;0.001, early vs late p=0.008, Figure 2B). Next, in MSP analysis, human PPARγ promoter was featured by typical CpG islands (Figure 3A). As the OA progresses, hypermethylation at PPARγ promoter (ND: 9%, Early-FAI: 34%, Late FAI-OA: 48%) was observed (Figure 3B), and ChIP assay confirmed DNMT3A interaction with the CpG PPARγ promoter area (Figure 3C). IL1β stimulus increased PPARγ promoter methylation for early (34% to 57%, p=0.016, Figure 3D) and late stages (48% to 79%, p=0.001, Figure 3D) resulting in suppression of PPARγ expression (P=0.073, Figure 3F). Contrary, treatment with 5Aza (a DNA demethylator) brought the level of methylation back to 37% for early FAI ( p=0.033, Figure 3D) and 46% for late FAI-OA (p&lt;0.001, Figure 3D), reversed the PPARγ suppression induced by IL1β (early- FAI p=0.009, and late FAI-OA ACs p&lt;0.001 Figure 3F) and decreased expression of MMP-13 and COL10A1 induced by IL1β (early-FAI p=0.009, Figure 4C and late FAI-OA ACs p&lt;0.001 Figure 3F). PPARγ inhibitor rescued cells from the catabolic phenotype. (Fig.3E, F), suggesting that restoration of PPARγ by 5Aza contributes significantly to the cartilage protective effect. Conclusions: This current study demonstrates that PPARγ expression was gradually suppressed via promoter hypermethylation during OA progression in hip FAI. Moreover, the inflammatory stimulus with IL1β further increased catabolic markers and enhanced PPARγ suppression via promoter excessive hypermethylation in human hip ACs. Notably, DNA demethylating agent (5 aza) prevents the IL1β induced PPARγ promoter hypermethylation rescuing PPARγ and alleviating cartilage degenerative damage. Certainly, for patients with symptomatic hip FAI, surgical correction should be prioritized to suppress inflammation, but our observations suggests that critical epigenetic dysregulation occurs during the progression of hip OA. Future investigations will be needed to confirm if regulation of these epigenetic changes could potentially complement surgical treatment to minimize OA progression in hip FAI.

EARLY TO MID-TERM OUTCOMES OF PERIACETABULAR OSTEOTOMY FOR DEVELOPMENTAL HIP DYSPLASIA AND FEMOROACETABULAR IMPINGEMENT: A STUDY OF 1,087 CASES USING THE NAHR DATASET

Periacetabular osteotomy (PAO) is an established treatment for developmental hip dysplasia (DDH) in young adults and can also be utilised in the management of femoroacetabular impingement (FAI) with acetabular retroversion. This study used a national registry to assess the outcomes of PAO for DDH and FAI.PAOs recorded in the UK Non-Arthroplasty Hip Registry between 2012 and November 2022 were identified along with recorded patient and surgical characteristics. Cases were grouped according to the primary pathology (DDH or FAI). Patient reported outcome measures (PROMs) captured included the International Hip Outcome Tool (iHOT)-12 (primary outcome) and the EuroQol-5 Dimensions (EQ-5D) index preoperatively and at 6 months, 1, 2, and 5 years post-operatively.1,087 PAOs were identified; 995 for DDH (91%), 98 for FAI (9%). Most patients (91%) were female. The DDH group were significantly older (mean 31.7 years) than the FAI group (25.4 years) but had similar body mass index (mean 25.7kg/m2). Overall, significant (all p&lt;0.0001) iHOT-12 and EQ-5D improvement (delta) vs baseline pre-operative scores were achieved at 6 months (mean iHOT-12 improvement +27.4 (95%CI 25.3 to 29.5); n=515) and maintained out to 5 years (+30.0 (21.4 to 38.6); n=44 [9.8% of those eligible for follow-up at 5 years]), at which point 71% and 55% of patients continued to demonstrate a score improvement greater than or equal to the minimum clinically important difference (≥13 points) and substantial clinical benefit (≥28 points) for iHOT-12 respectively.This study demonstrates excellent functional outcomes following PAO undertaken for DDH and FAI in the short to medium term in a large national registry.

Can Hip Passive Range of Motion Predict Hip Microinstability? A Comparative Study

Background: Hip microinstability is an increasingly recognized cause of pain and disability in young adults. It is unknown whether differences in passive hip range of motion (ROM) exist between patients with versus without hip microinstability. Hypothesis: Underlying ligamentous and capsular laxity will result in differences in clinically detectable passive ROM between patients with femoroacetabular impingement (FAI), patients with microinstability, and asymptomatic controls. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A retrospective review of all patients undergoing hip arthroscopy between 2012 and 2018 was conducted. Patients with a diagnosis of isolated microinstability based on intraoperative findings were identified and classified as having isolated FAI, instability, or FAI + instability. Patients without a history of hip injury were included as controls. Range of motion was recorded in the supine position for flexion, internal rotation, and external rotation. Univariate and multivariate analysis was performed on each measurement in isolation as well as combinations of motion to include total rotation arc, flexion + rotation arc, and flexion + 2× rotation arc Models were then created and tested to predict instability status. Results: In total, 263 hips were included: 69 with isolated instability, 50 with FAI, 50 with FAI + instability, and 94 control hips. A higher proportion of patients in the instability and FAI + instability groups were female compared with the FAI and control groups ( P &lt; .001). On univariate analysis, differences were found in all groups in all planes of motion ( P &lt; .001). Multivariable analysis demonstrated differences in all groups in flexion and flexion + rotation arc. In symptomatic patients, the best performing predictive model for hip microinstability was flexion + rotation arc ≥200° (Akaike information criterion, 132.3; P &lt; .001) with a sensitivity of 68.9%, specificity of 80.0%, positive predictive value of 89.1%, and negative predictive value of 51.9%. Conclusion: Patients with hip microinstability had significantly greater ROM than symptomatic and asymptomatic cohorts without hip microinstability. Symptomatic patients with hip flexion + rotation arc ≥200° were highly likely to have positive intraoperative findings for hip microinstability, whereas instability status was difficult to predict in patients with a flexion + rotation arc of &lt;200°.

Conservative Physiotherapy Treatment of Femoroacetabular Impingement

Abstract The femoro-acetabular impingement (FAI) syndrome is a motion-related disorder of the hip joint with premature contact between the acetabulum and the proximal femur. It is a relatively new clinical entity and no strict treatment protocols and guidelines have been established yet. Furthermore, patients are often misdiagnosed and not properly treated. We report a clinical case of a young adult female patient presenting with a bilateral FAI-CAM type deformity during the last 2 years. An individual progressive global elastic resistant training program was established which involved stimulation to all affected muscle groups using Pilates concept. Hip-specific and functional lower limb strengthening targeted the deep hip external rotators, abductors and flexors in the transverse, frontal, and sagittal planes. Improving the dynamic stability and Core stability was the main aim of the challenging physiotherapy treatment in this case. A good functional result was registered at 6 months follow up. All therapeutic activities were performed in a pain free range of motion which was of paramount importance for achieving excellent patient compliance and successful outcome respectively. The applied treatment strategy demonstrated to be reliable and could be a helpful tool in the armamentarium of contemporary physiotherapy when dealing with the FAI group of patients.

Characteristics of Biomechanical and Physical Function According to Symptomatic and Asymptomatic Acetabular Impingement Syndrome in Young Adults.

Femoroacetabular impingement (FAI) is caused by hip joint anomalies. Although asymptomatic and symptomatic FAI have been reported in young adults, information on biomechanical and functional characteristics of FAI is rare. We compared the subjective hip score, range of motion (ROM), dynamic balance, and hip strength between symptomatic FAI (FAIsym) and asymptomatic FAI (FAIasym) groups and healthy controls. Participants (n = 307; men: 155, women: 152) were classified according to morphological abnormalities and hip joint symptoms, comprising symptomatic FAI, asymptomatic FAI, and healthy controls. The Copenhagen Hip and Groin Outcome Score (HAGOS), hip ROM, Y-balance test (YBT), and isokinetic hip strength were measured. The types of FAI were not significantly differenent in both men and women. FAIsym exhibited significantly reduced HAGOS, whereas FAIasym showed no significant difference compared to the healthy group (men: healthy 91.7 vs. FAIasym 87.2 vs. FAIsym 49.9, women: healthy 91.7 vs. FAIasym 86.2 vs. FAIsym 53.9). Hip flexion, adduction, and internal and external rotation ROMs were only significantly reduced in symptomatic FAI. Asymptomatic and symptomatic FAI groups displayed significantly lower YBT scores than healthy controls (men healthy: 84.9 vs. FAIasym: 69.0 vs. FAIsym 58.7, women healthy 79.2 vs. FAIasym 64.0 vs. FAIsym 55.5). Isokinetic hip flexion, adduction, and abduction strengths were significantly lower in FAIsym. In conclusion, FAIasym showed no decrease in muscle strength but displayed reduced dynamic balance. Subjective satisfaction, ROM, muscle strength, and dynamic balance were lower in FAIsym compared to FAIasym and healthy groups.

Acetabular cartilage delamination: performance of MRI using arthroscopy as the standard of reference.

Femoroacetabular impingement (FAI) frequently leads to acetabular chondral delamination. Early identification and treatment of these cases is crucial to prevent further damage to the hip. To evaluate the accuracy of morphological signs of cartilage acetabular delamination in non-arthrographic magnetic resonance imaging (MRI) using intra-articular arthroscopic findings in patients undergoing FAI surgery. All hip MRI scans were assessed individually by three independent radiologists. Images were assessed for signs of delamination including the presence of a linear area of bright signal intensity along the acetabular subchondral bone and an area of darker tissue at the surface of the acetabular cartilage. All FAI patients underwent surgery; arthroscopy served as the standard of reference. The mean age of participants was 36.1±10.9 years with 36 (48.6%) women. In the FAI group, arthroscopic surgery showed acetabular chondral delamination in 37 hips. In all hips (including the controls), MRI signs of acetabular cartilage delamination showed an average sensitivity across the three raters of 73.0% with a specificity of 71.0%. In a separate analysis of only the FAI patients, a slightly higher sensitivity (77.7%) but lower specificity (66.7%) was demonstrated. The interrater reliability showed a moderate agreement (average [k]) across the raters (0.450). Performance of non-arthrographic MRI in diagnosing acetabular chondral delamination showed good results, yet inter-observer reproducibility among different radiologists was only moderate. Our results suggest that an increased level of awareness, for signs of delamination using MRI, will be helpful for detecting chondral delamination in patients with a history of FAI.

Poster 196: Articular Chondrocytes in Hip Femoroacetabular Impingement Present a Less Catabolic Phenotype than Late Stage of Disease

Objectives:Pathophysiologic mechanisms during osteoarthritis (OA) have been primarily identified using tissues harvested from end stage of disease. However, it is likely that the disease-initiating molecular changes have already occurred in early-stage diseased joints. Femoroacetabular impingement (FAI) has an etiologic role in up to 50% of hip osteoarthritis (OA) and offers a unique opportunity to study molecular changes during early stage OA. Cartilage samples from the impingement zone of FAI patients express catabolic inflammatory molecules. Previously, we have confirmed that DNA methyltransferase 3B (DNMT3B) regulates post-natal articular cartilage homeostasis and 4 aminobutyrate aminotransferase (ABAT) is a downstream target for DNMT3B and attenuates catabolic gene expression. The purpose of the present study is to examine the catabolic state of ACs during progression of disease in hip FAI, specifically, to investigate the catabolic phenotype and to assess the expression levels of DNMT3B and ABAT during early (FAI) and late stage disease (OA-FAI).Methods:Full-thickness cartilage samples were collected from the anterolateral head-neck junction (impingement zone) of 11 patients. 5 patients underwent hip preservation surgery for symptomatic cam FAI (early stage OA- FAI) and 6 patients underwent total hip replacement for advanced OA secondary to cam FAI (late stage FAI-OA). As a non-disease (ND) group, 4 healthy samples were procured from hip joint cadavers. A liberator was used to harvest full thickness tissue samples for cartilage explant cultures. The cartilage tissues were washed several times using antibiotics and incubated at 37 °C and 5% CO2 for 24h. Subsequently, the explants were cultured in unstimulated conditions (no-treatment), under anabolic (TGFβ) and catabolic stimulus (IL-1β) for 48h. After culture, sections were stained with safranin O and fast green for histological analysis and cartilage degeneration was graded based on the Mankin score. RNA was isolated from explants, gene expression was analyzed via qPCR for the following specific markers: GADPH (housekeeping gene), DNMT3B, ABAT, MMP-13, and Type X collagen (COL10A1) (Figure-1). Comparisons among three groups were performed using one-way analysis of variance followed by the post hoc Bonferroni correction test.Results:Histological Mankin-scores are shown in Figure-2. Cartilage samples without treatment in ND group showed normal hyaline cartilage. However, reduction in safranin-O staining with significant increase of Mankin-score was observed under catabolic stimulus of IL-1β (Figure-2A). Contrary, in early FAI and late FAI-OA group, degenerative changes including superficial irregularities with some clefts, cell cloning, and reduced staining was observed in unstimulated conditions and became more pronounced when treated with IL-1β (Figure-2A and B). Degenerative changes were alleviated by anabolic stimulus with TGFβ1 (Figure-2B). qPCR revealed that compared to ND group, the expression levels of ABAT, MMP-13 and COL10A1 were increase in the early-FAI and late FAI-OA confirming a catabolic phenotype. Contrary, expression of DNMT3B gradually declined as the disease progressed showing significant differences between early-FAI and late FAI-OA (Figure-3B). Remarkably, although histological findings were similar between early and late stage FAI, catabolic molecule expression varied between early and late stage of disease suggesting a more catabolic phenotype state for late stage of disease.Conclusions:This current study provides initial data regarding the catabolic state of human ACs in early and late stage of hip FAI disease and characterized a catabolic phenotype of ACs from impingement zone in FAI. Importantly, although histological findings were similar between early and late stage FAI, catabolic molecule expression varied suggesting a less catabolic phenotype for early stage of disease. Most interestingly, the expression of DNMT3B gradually decrease as the disease progresses, and ABAT expression increase. Identification of these changes of methylation profiles during disease progression can distinguish pre- and early disease states from end diseased state and could provide a potential intervention to stop the OA progression in the near future. Future interventional therapies will confirm if ACs from early stage of disease can be rescued to a normal phenotype.

Poster 197: Understanding the Biological Pathway of Progression of Hip OA Disease through Transcriptome Analysis

Poster 197: Understanding the Biological Pathway of Progression of Hip OA Disease through Transcriptome Analysis

Patients with cam-type femoroacetabular impingement demonstrate increased change in bone-to-bone distance during walking: A dual fluoroscopy study.

Cam-type femoroacetabular impingement (FAI) syndrome is a painful, structural hip disorder. Herein, we investigated hip joint mechanics through in vivo, dynamic measurement of the bone-to-bone distance between the femoral head and acetabulum in patients with cam FAI syndrome and morphologically screened controls. We hypothesized that individuals with cam FAI syndrome would have larger changes in bone-to-bone distance compared to the control group, which we would interpret as altered joint mechanics as signified by greater movement of the femoral head as it articulates within the acetabulum. Seven patients with cam FAI syndrome and 11 asymptomatic individuals with typical morphology underwent dual fluoroscopy imaging during level and inclined walking (upward slope). The change in bone-to-bone distance between femoral and acetabular bone surfaces was evaluated for five anatomical regions of the acetabulum at each timepoint of gait. Linear regression analysis of the bone-to-bone distance considered two within-subject factors (activityand region) and one between-subjects factor (group). Across activities, the change in minimum bone-to-bone distance was 1.38-2.54 mm for the cam FAI group and 1.16-1.84 mm for controls. In all regions except the anterior-superior region, the change in bone-to-bone distance was larger in the cam group than the control group (p ≤ 0.024). An effect of activity was detected only in the posterior-superior region where larger changes were noted during level walking than incline walking. Statement of clinical significance: Patients with cam FAI syndrome exhibit altered hip joint mechanics during the low-demand activity of walking; these alterations could affect load transmission, and contribute to pain, tissue damage, and osteoarthritis.

Muscle and Hip Contact Forces in Asymptomatic Men With Cam Morphology During Deep Squat.

Cam morphology is defined as an aspherical femoral head-neck junction that causes abnormal contact of the acetabular rim with the anterior hip. Imaging confirmation of the cam morphology, associated with clinical signs and pain in the hip or groin, is characterized as femoroacetabular impingement (FAI) syndrome. Although some individuals with cam morphology do not experience any symptoms, sparse studies have been done on these individuals. Understanding the way asymptomatic individuals generate muscle forces may help us to better explain the progression of the degenerative FAI process and discover better ways in preventing the onset or worsening of symptoms. The purpose of this study was to compare the muscle and hip contact forces of asymptomatic cam morphology (ACM) and FAI syndrome men compared to cam-free healthy controls during a deep squat task. This prospective study compared 39 participants, with 13 in each group (ACM, FAI, and control). Five deep squatting trials were performed at a self-selected pace while joint trajectories and ground reaction forces were recorded. A generic model was scaled for each participant, and inverse kinematics and inverse dynamics calculated joint angles and moments, respectively. Muscle and hip contact forces were estimated using static optimization. All variables were time normalized in percentage by the total squat cycle and both muscle forces and hip contact forces were normalized by body weight. Statistical non-parametric mapping analyses were used to compare the groups. The ACM group showed increased pelvic tilt and hip flexion angles compared to the FAI group during the descent and ascent phases of the squat cycle. Muscle forces were greater in the ACM and control groups, compared to the FAI group for the psoas and semimembranosus muscles. Biceps femoris muscle force was lower in the ACM group compared to the FAI group. The FAI group had lower posterior hip contact force compared to both the control and ACM groups. Muscle contraction strategy was different in the FAI group compared to the ACM and control groups, which caused different muscle force applications during hip extension. These results rebut the concept that mobility restrictions are solely caused by the presence of the cam morphology and propose evidence that symptoms and muscle contraction strategy can be the origin of the mobility restriction in male patients with FAI.

The hip asphericity angle: a novel angle for measurement of Cam-FAI correction

Abstract The alpha angle is routinely used for the diagnosis and quantitative description of the Cam deformity of the hip. However, a reliable identification of the femoral neck axis as its reference line can be difficult. Moreover, most cam resections include a reduction of the femoral neck diameter with an automatic posteromedial angulation of the femoral neck axis. In consequence, the reference axes for the pre- and postoperative alpha angles are different, and a comparison of both angles underlies a systematic error to relatively higher postoperative alpha angles. In order to avoid this systemic error, we propose the hip asphericity (HA) angle with a reference axis independent of the amount of bony resection. Two retrospective groups were formed, a ‘femoroacetabular impingement (FAI) group’ that had hip arthroscopy for cam resection and a ‘Control group’ without cam deformity. The alpha and HA angles were measured by three examiners. The measurements were repeated 1 month later. In the FAI group, offset correction was calculated using both angles. Statistically significant differences for both the alpha and the HA angles were found between the control and the preoperative FAI group as well as between the preoperative and postoperative FAI groups. The HA angle-correction by a mean of 27.5° was significantly higher in comparison to the alpha angle correction by a mean of 25.4°. The intertester and intratester reliability of both angles were not significantly different. The HA angle is a new and reliable radiographic parameter for measuring cam deformity and proves superior in measuring cam correction.

Is hip arthroscopy useful in the treatment of borderline dysplasia?: a case-control study

IntroductionSince arthroscopy remains a controversial treatment of hip dysplasia, our objective was to analyse its clinical and radiological results in a cohort of patients with dysplasia and compare them to controls with femoroacetabular impingement (FAI). Material and methodsWe retrospectively analysed a series of patients who underwent hip arthroscopy for the treatment of labral pathology; 29 of them with borderline hip dysplasia and 197 with FAI, comparing reoperations and joint survival. The diagnosis of borderline dysplasia was made with a lateral centre-edge angle greater than 18° but less than 25°. The average follow-up was 43 months. We performed a multivariate regression analysis to evaluate the association of reoperations with different demographic, radiological and intraoperative variables. ResultsSeven complications were registered in the FAI group (1 medically treated superficial wound infection, 3 pudendal nerve paraesthesias, 1 deep vein thrombosis and 2 heterotopic ossifications) and none in the dysplasia group. While 5 patients from the FAI group required a new surgery, none of the dysplasia group was re-operated (p=.38). After adjusting for confounders, reoperation showed a very strong association with the finding of osteochondral lesions during index surgery, with a coefficient of .12 (p<.001, 95%CI=.06-.17). ConclusionHip arthroscopy was useful in the treatment of borderline dysplasia, without non-inferior survival compared to the FAI group. We suggest indicating it carefully in dysplasia cases, whenever the symptoms of femoroacetabular friction prevail over those of instability.

¿Es útil la artroscopia de cadera para el tratamiento de la displasia limítrofe?: análisis de casos y controles

IntroductionSince arthroscopy remains a controversial treatment of hip dysplasia, our objective was to analyse its clinical and radiological results in a cohort of patients with dysplasia and compare them to controls with femoroacetabular impingement (FAI). Material and methodsWe retrospectively analysed a series of patients who underwent hip arthroscopy for the treatment of labral pathology; 29 of them with borderline hip dysplasia and 197 with FAI, comparing reoperations and joint survival. The diagnosis of borderline dysplasia was made with a lateral centre-edge angle greater than 18° but less than 25°. The average follow-up was 43 months. We performed a multivariate regression analysis to evaluate the association of reoperations with different demographic, radiological and intraoperative variables. ResultsSeven complications were registered in the FAI group (1 medically treated superficial wound infection, 3 pudendal nerve paraesthesias, 1 deep vein thrombosis and 2 heterotopic ossifications) and none in the dysplasia group. While 5 patients from the FAI group required a new surgery, none of the dysplasia group was re-operated (p=.38). After adjusting for confounders, reoperation showed a very strong association with the finding of osteochondral lesions during index surgery, with a coefficient of .12 (p<.001, 95%CI=.06-.17). ConclusionHip arthroscopy was useful in the treatment of borderline dysplasia, without non-inferior survival compared to the FAI group. We suggest indicating it carefully in dysplasia cases, whenever the symptoms of femoroacetabular friction prevail over those of instability.

Distinct Pattern of Inflammation of Articular Cartilage and the Synovium in Early and Late Hip Femoroacetabular Impingement

Background: The molecular mechanism of how femoroacetabular impingement (FAI) morphology leads to hip osteoarthritis (OA) is yet to be determined. The expression and location of inflammation-related molecules during early- and late-stage FAI have not been previously described. Moreover, the characterization of intra-articular inflammation away from the cam deformity as well as the nature of adjacent synovial tissue have also not been extensively reported. Hypothesis: Early-stage FAI has a similar expression of inflammation-related markers in the head-neck and acetabular cartilage but less synovitis than late-stage FAI. Study Design: Controlled laboratory study. Methods: Head-neck cartilage, acetabular cartilage, and synovial samples were obtained from patients undergoing hip preservation surgery for the treatment of symptomatic cam FAI (early FAI group; n = 15) and advanced OA secondary to cam FAI (late FAI group; n = 15). Samples procured from healthy young adult donors served as the control group (n = 7). Cartilage degeneration was assessed by histology, and the expression of inflammation-related proteins (interleukin–1 beta [IL-1β], matrix metalloproteinase–13 [MMP-13], a disintegrin and metalloproteinase with thrombospondin motifs–4 [ADAMTS-4], type II collagen [COL2], and aggrecan neoepitope [NITEGE]) was measured by immunostaining. Synovial samples in the early and late FAI groups were examined for synovitis and the expression of IL-1β. Results: Head-neck cartilage in the early FAI group showed significantly more degeneration than the control group and an increased expression of inflammation-related proteins (IL-1β: 69.7% ± 18.1% vs 20.2% ± 4.9%, respectively; MMP-13: 79.6% ± 12.6% vs 25.3% ± 9.5%; ADAMTS-4: 83.9% ± 12.2% vs 24.3% ± 11.1%; NITEGE: 89.7% ± 7.7% vs 39.8% ± 20.5%) (P < .001). Head-neck and acetabular cartilage in the early and late FAI groups showed a similar degree of degeneration. Moreover, a similar expression of inflammation-related proteins was observed between the early and late FAI groups for head-neck cartilage (IL-1β: 69.7% ± 18.1% vs 72.5% ± 13.2%; MMP-13: 79.6% ± 12.6% vs 71.4% ± 18.8%; ADAMTS-4: 83.9% ± 12.2% vs 82.6% ± 12.5%; COL2: 93.6% ± 3.9% vs 92.5% ± 5.8%; NITEGE: 89.7% ± 7.7% vs 95.7% ± 4.7%) and acetabular cartilage (IL-1β: 83.3% ± 24.8% vs 80.7% ± 15.6%; MMP-13: 94.3% ± 9.7% vs 85.2% ± 12.3%; ADAMTS-4: 98.5% ± 2.3% vs 98.4% ± 3.4%; COL2: 99.8% ± 0.7% vs 99.7% ± 1.1%; NITEGE: 96.7% ± 6.7% vs 99.2% ± 2.2%). In contrast, synovitis was minimal with a low expression of IL-1β in the early FAI group compared with the late FAI group. Conclusion: Hip cartilage exhibited an OA phenotype in patients with early-stage FAI, similar to what was observed in hip OA secondary to FAI. Severe synovitis was only evident with late-stage FAI. Clinical Relevance: This study supports the concept that early hip impingement is associated with cartilage degeneration and catabolism.

Differences in articular hip cartilage gene expression between femoroacetabular impingement (FAI) and end-stage hip osteoarthritis

Objectives:The morphological deformities in Femoroacetabular Impingement (FAI) have been associated with hip osteoarthritis (OA), however the molecular mechanisms for OA initiation and progression are poorly understood. The purpose of this study was to use whole genome RNA sequencing to characterize differences in gene expression articular cartilage samples isolated from patients undergoing surgery for FAI and idiopathic OA. We hypothesized that there would be significant differences in genes expression in pathways related to inflammation as well as cartilage and bone turnover.Methods:20 patients undergoing either hip arthroscopy for FAI (5 male, 5 female) or total hip arthroplasty (5 male, 5 female) for end-stage osteoarthritis were included in the study. FAI patients required a Cam deformity with an Alpha Angle greater than 55 while patients with dysplasia (LCEA<25) or prior hip surgery were excluded. Exclusion criteria for the THA cohort included dysplasia, and post-traumatic OA or inflammatory OA. Cartilage samples were obtained over the Cam deformity prior to femoroplasty in the FAI group or over anterosuperior femoral head-neck junction in the OA group following extraction of the femoral head. Following RNA isolation, Next Generation RNA sequencing was performed to evaluate gene expression. Differential expression data was incorporated into the Ingenuity Pathway Analysis (IPA) platform to identify differences in canonical signaling pathways associated with osteoarthritis.Results:There were 3531 genes that were significantly differentially expressed between the FAI and OA cohorts. Of these, there were 27 genes that were upregulated by a greater than 2 log-fold change in the OA cohort and 524 genes that were upregulated by a greater than 2 log-fold change in the FAI cohort. There was significant differential expression in genes related to cartilage metabolism (Table 1) and canonical osteoarthritis pathways involving BMP, TGFβ, and Wnt signaling. (Table 2). Additionally, FAI samples had significant upregulation of EGF-ERBB mediated signaling which compared to osteoarthritic tissue.Conclusion:The results of the present study support our hypothesis that there are significant differences in gene expression between FAI and OA samples in multiple pathways that are implicated in osteoarthritis. Osteoarthritis samples had increased expression of cartilage breakdown and inflammation while femoroacetabular impingement samples had greater expression of chondroprotective genes. Further study of cartilage samples from FAI patients may provide insight into the molecular mechanisms of osteoarthritis progression.Table 1.Differential gene expression in genes related to cartilage metabolism. Osteoarthritic samples had elevated COL10, 24, 8, and 9 genes while FAI had elevated COMP, COL4, and COL6 genes.Cartilage MetabolismUpregulated OA Padj Upregulated FAI Padj COL10A10.0001638COMP0.034951COL24A10.0117991COL4A35.96E-33COL8A10.0274064COL4A49.46E-14COL9A10.0004479COL4A51.49E-14COL9A20.0090092COL6A69.56E-05ADAMTS40.0003928COL6A62.23E-08Table 2.Differential expression of genes previously implicated in osteoarthritis. Osteoarthritis samples had elevated markets of end stage cartilage breakdown (ADAMTS4, MMP13, TNF) while FAI samples had increased expression of chondroprotective genes (FGF18, WNT 16, BMPR18)Canonical Osteoarthritis PathwayUpregulated OA Upregulated FAI GREM13.32E-12SMAD40.002188MMP13.24E-05C/EBP2.32E-04COL10A11.64E-04WNT160.001925FRZB3.32E-08PGC12.11E-07MMP132.77E-04FGF189.67E-09MATN30.00205VEGFD1.03E-12 MMP30.007351SOX100.000216ADAMTS43.93E-04NOS11.87E-34Osteopontin0.006119DKK20.007801MMP90.004763GDF61.08E-07S1PR30.003633BMPR1B1.31E-22TNF0.001382 RUNX21.19E-04 SPHK18.83E-05 TGFB13.44E-04 CTR0.012398 RANK3.77E-06

Periacetabular Osteotomy for Developmental Dysplasia of the Hip and Femoroacetabular Impingement: A Study Using the U.K. Non-Arthroplasty Hip Registry (NAHR) Data Set.

Periacetabular osteotomy (PAO) is a well-recognized procedure for the treatment of hip dysplasia in young adults and can be used for the surgical management of femoroacetabular impingement (FAI) with acetabular retroversion. The aim of this study was to use a national database to assess the outcomes of PAO for developmental dysplasia of the hip (DDH) and for FAI. All patients in whom an isolated PAO had been performed between January 2012 and February 2019 were identified in the Non-Arthroplasty Hip Registry (NAHR). Their outcomes were assessed using the EuroQol-5 Dimensions (EQ-5D) index and the International Hip Outcome Tool (iHOT)-12 preoperatively and then at 6 months, 12 months, and 2 years postoperatively. Six hundred and thirty (630) PAOs were identified, with 558 (89%) performed for DDH and 72 (11%) performed for FAI. Most patients (90%) were female. The mean age in the DDH group (31.2 years) was significantly higher (p < 0.0001) than that in the FAI group (26.5 years). There were no other significant between-group demographic differences. Preoperatively and at each follow-up time-period, iHOT-12 scores were better in the DDH group than in the FAI group; however, only the preoperative scores differed significantly. There was significant improvement between the preoperative and 6-month iHOT-12 and EQ-5D index scores in both the DDH and the FAI group. This improvement was maintained at 12 months postoperatively, by which time almost 90% of the patients had achieved the minimum clinically important difference (MCID) in their iHOT-12 score. This study shows that PAO is a successful surgical intervention for DDH and FAI in the short term, with significant improvement in patient-reported outcome scores that is maintained up to 2 years postoperatively. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.