Hip Femoroacetabular Impingement Research Articles

Interleukin-6 and Interleukin-8 Gene Expressions Differ Between Male and Female Patients at Time of Hip Arthroscopy for Femoroacetabular Impingement Syndrome

To identify key molecular components within the femoroacetabular impingement hip and compare the findings between male and female patients across varying age groups. All patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS) without hip dysplasia were included. During hip arthroscopy, performed at University of Wisconsin Health, loose articular cartilage, excess synovium, damaged labral tissue, and minimal adipose tissue were debrided only as needed for visualization and tissue repair purposes and collected. Tissue was processed and used for quantitative polymerase chain reaction (qPCR). Genes were selected for qPCR on the basis of their associated function in inflammation and/or extracellular matrix remodeling during the progression of osteoarthritis. A total of 91 male (M) and female (F) patients 15 to 58 years old were included in the study. qPCR results indicated that Interleukin-6 (P < .05, 95% confidence interval [CI] 0.047-0.083 F, 0.070-0.12 M) and Interleukin-8 (P=.04, 95% CI 0.059-0.10 F, 0.082-0.18 M) were significantly greater in male patients compared with female patients regardless of age, and IL6 (P= .02, 95% CI [0.026-0.070] F, [0.067-0.17] M), Interleukin-1ß (P < .01 95% CI [0.013-0.063] F, [0.073-0.25] M), and Matrix metalloproteinase-13 (P= .047, 95% CI [0.0051-0.017] F, [0.0084-0.052] M) were significantly greater in male patients younger than 20 years old compared with female patients younger than 20 years old. In patients with FAIS, there are significant differences between male and female patients in the biomarkers present in the affected hip at the time of surgery. Male patients have greater levels of IL6 and IL8 and male patients younger than 20 years of age have greater levels of IL1β, IL6, and MMP13 compared with age-matched female patients. A better understanding of the molecular markers present during varying stages of FAIS and in patients of different ages will help characterize the pathologic process behind FAIS. This may also help define future methods of targeted treatment and prevention of disease progression.

Prevalence of hip femoroacetabular impingement deformities in high-level (La Liga) male professional football players.

Femoroacetabular impingement (FAI) is considered one of the main causes of hip osteoarthritis in young adults, especially in athletes. In recent years, morphological changes in FAI in the hip have been linked to early and intense sports participation, but studying top-level athlete samples is not easy. This paper presents the prevalence of FAI radiological markers in 120 active white male professional football players in the Spanish First Division League (La Liga) and compares the morphological changes with those of a control group of healthy individuals without significant sport activity. The precontract medical evaluation hip X-rays of 120 white male professional football players from four different First Division Spanish football teams were prospectively filed and retrospectively reviewed by a dedicated skeletal radiologist. The footballers' hip X-rays were compared with those of a control group of 80 healthy individuals (age-sex matched) without significant sport activity (obtained from routine work medical checks). The femoral head-neck deformity associated with the Cam type of femoroacetabular impingement was observed in 61.6% of professional football players and only in 11.6% of the control group (p <0.01). The presence of "herniation pit" (11.6%) and os acetabuli (13.3%) also reached statistical significance in the professional football players group. In the other analyzed parameters, no statistically significant differences between the groups were observed. White professional top-level football players have an increased incidence of abnormal lateral epiphyseal extension ("pistol grip deformity"), os acetabuli and herniation pits.

UTE T2* cartilage mapping in the hip: a pilot study assessing cartilage in patients with femoroacetabular impingement.

UTE T2* cartilage mapping use in patients undergoing femoroacetabular impingement (FAI) has been lacking but may allow the detection of early cartilage damage. To assess the reproducibility of UTE T2* cartilage mapping and determine the difference in UTE T2* values between FAI and asymptomatic patients and to evaluate the correlation between UTE T2* values and patient-reported symptoms. Prospective evaluation of both hips (7 FAI and 7 asymptomatic patients). Bilateral hip 3-T MRI scans with UTE T2* cartilage maps were acquired. A second MRI scan was acquired 1-9 months later. Cartilage was segmented into anterosuperior, superior, and posterosuperior regions. Assessment was made of UTE T2* reproducibility (ICC). Mean UTE T2* values in patients were compared (t-tests) and correlation was made with patient-reported outcomes (Spearman's). ICCs of mean UTE T2* were as follows: acetabular, 0.82 (95% CI=0.50-0.95); femoral, 0.76 (95% CI=0.35-0.92). Significant strong correlation was found between mean acetabular UTE T2* values and iHOT12 (ρ = -0.63) and moderate correlation with mHHS (ρ = -0.57). There was no difference in mean UTE T2* values between affected vs. non-affected FAI hips. FAI-affected hips had significantly higher values in acetabulum vs. asymptomatic patients (13.47 vs. 12.55 ms). There was no difference in mean femoral cartilage values between the FAI-affected hips vs. asymptomatic patients. The posterosuperior femoral region had a higher mean value in non-affected FAI hips vs. asymptomatic patients (12.60 vs. 11.53 ms). UTE T2* cartilage mapping had excellent reproducibility. Affected FAI hips had higher mean acetabular UTE T2* values than asymptomatic patients. Severity of patient-reported symptoms correlates with UTE T2* acetabular cartilage values.

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.

Poster 116: Integrated scRNA-seq and spatial transcriptomics analysis uncovers distinct cellular populations and transcriptomes in human hip synovium between patients with femoroacetabular impingement and osteoarthritis.

Objectives: Osteoarthritis (OA) is a common degenerative joint disease marked by joint dysfunction and chronic pain. Previous studies have outlined a variety of complex factors associated with cartilage degradation, inflammation, and pathological changes in knee synovium. However, hip and knee OA have been established as immunologically distinct types of joint diseases due to unique cytokine profiles of synovial fluid, and data regarding hip OA synovium is scarce1. Evidence suggests that primary hip OA may result from cam-type femoroacetabular impingement (FAI). Thus, cam-type FAI has been considered a unique early-phase model of hip OA, allowing scientists to identify regulators implicated in hip OA development. Integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (Spatial-seq) provides a powerful means to better understand unique genetic markers underlying signaling pathways and cellular interactions that may be involved in disease progression (i.e., FAI to hip OA). In this study, we hypothesize that FAI and hip OA patients have distinct transcriptomic profiles and signaling pathways in their synovial tissues. We aim to identify the underlying molecular mechanisms by using scRNA-seq, Spatial-seq, and bioinformatic analyses. Methods: De-identified human hip synovial tissues were harvested from patients diagnosed with cam- type FAI or with OA (and accompanying cam morphology) according to approved IRB protocols at the University of Rochester (UR). Tissue samples were digested for scRNA-seq and sectioned for Spatial-seq separately and submitted to UR Genomics Research Center (10X Genomics). Distinct cell populations and differentially expressed genes (DEGs) were identified using bioinformatic tools including Seurat2, Monocle3, RcisTarget4, and CellChat5 R packages. Functional analysis for identified cell subsets was annotated by Gene Ontology term6. Differentiation trajectories of non-hematopoietic cells and cell-cell crosstalk were also evaluated. Results: Unsupervised clustering of FAI and OA hip synovial cells identified four major conserved groups: NK cells, endothelial cells, myeloid cells, and non-hematopoietic cells. Sub-clustering of integrated FAI and OA non-hematopoietic cells further yielded 5 distinct cell types including lining, sublining and transitional fibroblast-like synoviocytes (FLS) as well as endothelial cells and pericytes (Fig. 1A). In comparison to FAI synovium, OA synovium exhibited 4.5-, 5- and 8.5-fold increase in IL11+/CD82+ sublining FLS (cluster 5), pericytes (cluster 7) and SPP1+/KDR+ capillary endothelial cells (cluster 9), respectively (Fig. 1B). To further investigate the origin of these populations, we performed pseudotime analysis and revealed that pericytes may differentiate from C34+/C3+/CXCL14+ sublining perivascular FLS (cluster 6) (Fig. 2A)6. To determine the putative transcription factors (TFs) regulating the differentiation process between these two cell populations, we identified that KLF4, SOX5 and CREB3L2 (CAMP Responsive Element Binding Protein 3 Like 2) are potential key regulators using DNA-binding motif analysis. We also observed an opposite trend in expression of KLF4 and CREB3L2, with the highest expression levels of KLF4 in sublining perivascular FLS (Fig. 2B). Importantly, by integrating scRNA-seq and Spatial-seq datasets, we were able to map spatial location of identified cell clusters in the hip joint synovium, allowing us to further interrogate cell-cell crosstalk. For example, we observed that pericytes are in close proximity to SPP1+/KDR+ capillary endothelial cells (cluster 9) and identified that VISFATIN- (ITGA5+ITGB1) and SPP1-CD44 are critical signaling pathways between these two cell populations in OA synovium (Fig. 3B). Conclusions: OA is the most prevalent degenerative joint disorder and is a primary cause of worldwide disability without any available disease modifying therapies. We believe that our findings will reveal key genetic markers related to hip OA progression and facilitate the development of targeted drug deliveries for future therapeutic applications. Our scRNA-seq analysis revealed unique transcriptomic patterns in the synovial cells between FAI and hip OA patients. Integration of non-hematopoietic cells revealed a significant increase in the number of pericytes and endothelial cells present in OA vs. FAI synovium. This is supported by the evidence of increased vasculature in OA, which in turn may promote enhanced infiltration of myeloid cells, cytokines and chemokines into the synovium, leading to an advanced joint inflammation and disease progression7. Furthermore, we identified that both pericytes and capillary endothelial cells can express visfatin (an adipokine) and may modulate synovial inflammation in OA via integrin-mediated signaling pathways8. This observation aligns with previous studies that highlight a significant contribution of endothelial cell-pericyte interactions to OA pathogenesis8. In addition, our finding of decreased expression of KLF4 in pericytes is consistent with previous reports showing that KLF4 inactivation enhances the expression of pericyte markers9. Our next step is to integrate our scRNA- seq and Spatial-seq datasets of non-hematopoietic cells with myeloid cells to further elucidate how altered cell-cell crosstalk and signaling pathways in synovium may lead to hip OA progression. Indeed, we have analyzed myeloid cells separately, and observed elevated accumulation of “hybrid” macrophages expressing pro- and anti-inflammatory markers (IL10+/IL1 +/IL1 +) in the hip OA compared to FAI synovium.

Large Hip Impingement Area and Subspine Hip Impingement in Patients With Absolute Femoral Retroversion or Decreased Combined Version.

It remains unclear if femoral retroversion is a contraindication for hip arthroscopy in patients with femoroacetabular impingement (FAI). To compare the area and location of hip impingement at maximal flexion and during the FADIR test (flexion, adduction, internal rotation) in FAI hips with femoral retroversion, hips with decreased combined version, and asymptomatic controls. Cross-sectional study; Level of evidence, 3. Twenty-four symptomatic patients (37 hips) with anterior FAI were evaluated. All patients had femoral version (FV) <5° according to the Murphy method. Two subgroups were analyzed: 13 hips with absolute femoral retroversion (FV <0°) and 29 hips with decreased combined version (McKibbin index <20°). All patients were symptomatic and had anterior groin pain and a positive anterior impingement test ; all had undergone pelvic computed tomography (CT) scans to measure FV. The asymptomatic control group consisted of 26 hips. Dynamic impingement simulation of maximal flexion and FADIR test at 90° of flexion was performed with patient-specific CT-based 3-dimensional models. Extra- or intra-articular hip impingement area and location were compared between the subgroups and with control hips using nonparametric tests. Impingement area was significantly larger for hips with decreased combined version (<20°) versus combined version (≥20°) (mean ± SD; 171 ± 140 vs 78 ± 55 mm2; P = .012) and was significantly larger for hips with FV <0° (absolute femoral retroversion) vs FV >0° (P = .025). Hips with absolute femoral retroversion had a significantly higher frequency of extra-articular subspine impingement versus controls (92% vs 0%; P < .001), compared to 84% of patients with decreased combined version. Intra-articular femoral impingement location was most often (95%) anterosuperior and anterior (2-3 o'clock). Anteroinferior femoral impingement location was significantly different at maximal flexion (anteroinferior [4-5 o'clock]) versus the FADIR test (anterosuperior and anterior [2-3 o'clock]) (P < .001). Patients with absolute femoral retroversion (FV <0°) had a larger hip impingement area, and most exhibited extra-articular subspine impingement. Preoperative FV assessment with advanced imaging (CT/magnetic resonance imaging) could help to identify these patients (without 3-dimensional modeling). Femoral impingement was located anteroinferiorly at maximal flexion and anterosuperiorly and anteriorly during the FADIR test.

Epigenetic dysregulation of articular cartilage during progression of hip femoroacetabular impingement disease.

Femoroacetabular impingement (FAI) is an important trigger of hip osteoarthritis (OA). Epigenetic changes in DNA methyltransferase 3B (DNMT3B) attenuate catabolic gene expression in cartilage hemostasis. This study aimed to examine the articular chondrocyte catabolic state and DNMT3B and 4-aminobutyrate aminotransferase promoter (ABAT) expression during OA progression in FAI. Cartilage samples were collected from the impingement zone of 12 patients with cam FAI (early-FAI) and 12 patients with advanced OA secondary to cam FAI (late-FAI-OA). Five healthy samples were procured from cadavers (ND: nondiseased). Explants were cultured under unstimulated conditions, catabolic stimulus (IL1β), or anabolic stimulus (TGFβ). Histology was performed with safranin-O/fast-green staining. Gene expression was analyzed via qPCR for GAPDH, DNMT3B, ABAT, MMP-13, COL10A1. Methylation specific PCR assessed methylation status at the ABAT promoter. Cartilage samples in early-FAI and late-FAI-OA showed a histological OA phenotype and increased catabolic marker expression (MMP13/COL10A1, ND vs.early-FAI, p = 0.004/p < 0.001, ND vs.late-FAI-OA, p < 0.001/p < 0.001). RT-PCR confirmed DNMT3B underexpression (ND vs.early-FAI, p < 0.001, early-FAI vs.late-FAI-OA, p = 0.016) and ABAT overexpression (ND vs.early-FAI, p < 0.001, early vs.late-FAI-OA, p = 0.035) with advanced disease. End-stage disease showed ABAT promoter hypomethylation. IL1β stimulus accentuated ABAT promoter hypomethylation and led to further ABAT and catabolic marker overexpression in early-FAI and late-FAI-OA while TGFβ normalized these alterations in gene expression. Catabolic and epigenetic molecule expression suggested less catabolism in early-stage disease. Sustained inflammation induced ABAT promoter hypo-methylation causing a catabolic phenotype. Suppression of ABAT by methylation control could be a new target for therapeutic intervention to prevent OA progression in hip FAI.

Clinical and Radiographic Criteria Define “Acceptable” Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study

To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92%agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincer-type FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.

Automated measurement of alpha angle on 3D-magnetic resonance imaging in femoroacetabular impingement hips: a pilot study

BackgroundFemoroacetabular impingement (FAI) syndrome is an established pre-osteoarthritic condition. Diagnosis is based on both clinical and radiographic parameters. An abnormal manually calculated alpha angle in magnetic resonance imaging (MRI) is traditionally utilized to diagnose abnormal femoral head-neck offset. This pilot study aimed to assess the feasibility of automated alpha angle measurements in patients with FAI syndrome, and to compare automated with manual measurements data with regard to the time and effort needed in each method.MethodsAlpha angles were measured with manual and automated techniques, using postprocessing software in nineteen hip MRIs of FAI syndrome patients. Two observers conducted manual measurements. Intra- and inter-observer reproducibility and correlation of manual and automated alpha angle measurements were calculated using intra-class correlation (ICC) analysis. Both techniques were compared regarding the time taken (in minutes) and effort required, measured as the amount of mouse button presses performed.ResultsThe first observer’s intra-observer reproducibility was good (ICC 0.77; p < 0.001) while the second observer’s was good-to-excellent (ICC 0.93; p < 0.001). Inter-observer reproducibility between both observers in the first (ICC 0.45; p < 0.001) and second (ICC 0.56; p < 0.001) manual alpha angle assessment was moderate. The intra-class correlation coefficients between manual and automated alpha angle measurements were ICC = 0.24 (p = 0.052; observer 1, 1st measurement), ICC = 0.32 (p = 0.015; observer 1, 2nd measurement), ICC = 0.50 (p < 0.001; observer 2, 1st measurement), and ICC = 0.45 (p < 0.001; observer 2, 2nd measurement). Average runtime for automatic processing of the image data for the automated assessment was 16.6 ± 1.9 min. Automatic alpha angle measurements took longer (time difference: 14.6 ± 3.9 min; p < 0.001) but required less effort (difference in button presses: 231 ± 23; p < 0.001). While the automatic processing is running, the user can perform other tasks.ConclusionsThis pilot study demonstrates that objective and reliable automated alpha angle measurement of MRIs in FAI syndrome hips is feasible.Trial registration The Ethics Committee of the University of Düsseldorf approved our study (Registry-ID: 2017084398).

The Impact of Hip Dysplasia on CAM Impingement.

Predisposing factors for CAM-type femoroacetabular impingement (FAI) include acetabular protrusion and retroversion; however, nothing is known regarding development in dysplastic hips. The purpose of this study was to determine the correlation between CAM-type FAI and developmental dysplastic hips diagnosed using X-ray and rotational computed tomography. In this retrospective study, 52 symptomatic hips were included, with a mean age of 28.8 ± 7.6 years. The inclusion criteria consisted of consecutive patients who suffered from symptomatic dysplastic or borderline dysplastic hips and underwent a clinical examination, conventional radiographs and rotational computed tomography. Demographics, standard measurements and the rotational alignments were recorded and analyzed between the CAM and nonCAM groups. Among the 52 patients, 19 presented with CAM impingement, whereas, in 33 patients, no signs of CAM impingement were noticed. For demographics, no significant differences between the two groups were identified. On conventional radiography, the acetabular hip index as well as the CE angle for the development of CAM impingement were significantly different compared to the nonCAM group with a CE angle of 21.0° ± 5.4° vs. 23.7° ± 5.8° (p = 0.050) and an acetabular hip index of 25.6 ± 5.7 vs. 21.9 ± 7.3 (p = 0.031), respectively. Furthermore, a crossing over sign was observed to be more common in the nonCAM group, which is contradictory to the current literature. For rotational alignment, no significant differences were observed. In dysplastic hips, the CAM-type FAI correlated to a lower CE angle and a higher acetabular hip index. In contrast to the current literature, no significant correlations to the torsional alignment or to crossing over signs were observed.

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.

Two-Tiered Resection of Cam Lesions in Hip Femoroacetabular Impingement: Optimizing Femoral Head Sphericity

Hip arthroscopy is one of the most rapidly growing fields in orthopaedic surgery. One of the most frequent pathologies treated with hip arthroscopy remains femoroacetabular impingement, which is addressed by labral repair and femoral osteoplasty. The most commonly cited reason for failure of arthroscopic treatment of femoroacetabular impingement is under-resection of the cam lesion. Surgeons frequently use evaluations of preoperative images, intraoperative fluoroscopy, and dynamic range of motion to ensure adequate resection. In this article, we describe a reproducible and standardized technique to assist in appropriate resection. This is achieved by a 2-tiered resection technique: Tier 1 aims to set the depth of resection and restore the head-neck offset. Tier 2 then matches the depth of the resection set by tier 1 and allows for retention of appropriate transition of the proximal convexity to the distal concavity seen in more ideally shaped femoral heads. With this technique, we offer a tool to avoid under-resection in the area of maximal conflict while simultaneously minimizing the risk of proximal over-resection and thus compromising the fluid seal dynamics of the joint in deeper flexion angles.

A Novel Model of Hip Femoroacetabular Impingement in Immature Rabbits Reproduces the Distinctive Head-Neck Cam Deformity

Background: Femoroacetabular impingement (FAI) is a leading cause of hip pain in young adults and often leads to degenerative osteoarthritis (OA). A small animal model of hip deformities is crucial for unraveling the pathophysiology of hip OA secondary to FAI. Purposes: To (1) characterize a new minimally invasive surgical technique to create a proximal femoral head–neck deformity in a skeletally immature rabbit model and (2) document the effect of an injury to the medial proximal femoral epiphysis on head–neck morphology at 28 days after the injury. Study Design: Controlled laboratory study. Methods: Six-week-old New Zealand White rabbits (n = 10) were subjected to right hip surgery, with the left hip used as a control. An epiphyseal injury in the medial femoral head was created using a 1.6-mm drill. Hips were harvested bilaterally at 28 days after surgery. Alpha and epiphyseal shaft angles were measured on radiographs. Alpha angles at the 1- and 3-o’clock positions were measured on the oblique axial plane of micro–computed tomography images. Bone bar formation secondary to growth plate injuries was confirmed using alcian blue hematoxylin staining. Results: All hips in the study group showed a varus–type head-neck deformity, with lower epiphyseal shaft angles on anteroposterior radiographs versus those in the control group (133°± 8° vs 142°± 5°, respectively; P = .022) and higher epiphyseal shaft angles on lateral radiographs (27°± 12° vs 10°± 7°, respectively; P < .001). The mean alpha angles in the study group were higher at both the 1- (103°± 14° vs 46°± 7°, respectively; P < .002) and 3-o’clock (99°± 18° vs 35°± 11°, respectively; P < .002) positions than those in the control group. Alcian blue hematoxylin staining of all hips in the study group indicated that the injured physis developed a bony bar, leading to growth plate arrest on the medial femoral head. Conclusion: The proposed model led to growth arrest at the proximal femoral physis, resulting in a femoral head–neck deformity similar to human FAI. Clinical Relevance: Our novel small animal model of a femoral head–neck deformity is a potential platform for research into the basic mechanisms of FAI disease progression and the development of disease–modifying therapies.

Capsule-Preserving Approach to Arthroscopic Decompression of the Anterior Inferior Iliac Spine

Hip arthroscopy techniques have evolved to treat a wide range of extra-articular pathologies. Subspine impingement commonly occurs in femoroacetabular impingement, particularly in athletes with a high range of motion, patients with low degrees of femoral version, and those with large subspine deformities. A reliable technique that preserves the hip capsule would be helpful for hip arthroscopy surgeons. This note details our technique using pericapsular windows proximal to the interportal capsulotomy to access and decompress a subspine deformity in the setting of hip femoroacetabular impingement.

Preoperative risk factors in hip arthroscopy.

Arthroscopic surgery is a usual technique to repair hip femoroacetabular impingement. Correlation exists among surgical indication, postoperative evolution, the final result, and the necessity of prosthesis in the near future. The assessment of specific parameters allowing us to evaluate the prognosis becomes vital to improve the results. The objective of this study is to check the variables found in patients with femoroacetabular impingement (FAI) treated with hip arthroscopy, and determine which of these variables would serve as key indicators in predicting the need for subsequent arthroplasty. Data from FAI surgical indications (age, weight, height, BMI, gender, side, radiographic Tönnis degree, cartilage lesion degree by Acetabular Labrum Articular Disruption (ALAD) degree, VAS value, HOS, mHHS and WOMAC) were collected from cases which should have had a minimum monitoring period of 2years from 2007 to 2017. The results of the group which needed prosthesis were compared to the results of the ones who did not. Among 452 patients who were monitored for an average of 5.8years, 82 (18.1%) required conversion to prosthesis. The variables that indicated relatively high risk were fourth-degree acetabular labrum articular disruption (ALAD) chondral injury, preoperative radiographic Grade 2 Tönnis classification, age of over 55years, WOMAC over 45 points, and HOS-ADL under 50 points. There were no significant differences between side, gender, VAS level, nor HOS. The presence of chondral injuries such as acetabular labrum articular disruption (ALAD) 4, radiographic Grade 2 Tönnis classification, higher age, higher BMI, and worse WOMAC, along with mHHS and HOS-ADL preoperative results, are factors which lead to a poor prognosis following FAI hip arthroscopic surgery, increasing the risk of prosthetic conversion in the short or medium term. Level IV.

Best Practices: Hip Femoroacetabular Impingement.

OBJECTIVE. Imaging plays a critical role in the assessment of patients with femoroacetabular impingement (FAI). With better understanding of the underlying pathomechanics and advances in joint-preserving surgery, there is an increasing need to define the most appropriate imaging workup. The purpose of this article is to provide guidance on best practices for imaging of patients with FAI in light of recent advances in corrective FAI surgery. CONCLUSION. Pelvic radiography with dedicated hip projections is the basis of the diagnostic workup of patients with suspected FAI to assess arthritic changes and acetabular coverage and to screen for cam deformities. Chondrolabral lesions should be evaluated with unenhanced MRI or MR arthrography. The protocol should include a large-FOV fluid-sensitive sequence to exclude conditions that can mimic or coexist with FAI, radial imaging to accurately determine the presence of a cam deformity, and imaging of the distal femoral condyles for measurement of femoral torsion. CT remains a valuable tool for planning of complex surgical corrections. Advanced imaging, such as 3D simulation, biochemical MRI, and MR arthrography with application of leg traction, has great potential to improve surgical decision-making. Further research is needed to assess the added clinical value of these techniques.

Characterization of version in the dysplastic hip and the need for subsequent femoral derotational osteotomy after periacetabular osteotomy.

Hip dysplasia is a three-dimensional pathomechanical condition that is often more complex than the standard method of measuring lateral center edge angle (CEA) can quantify. Yet there is a paucity of literature examining the differences in version seen between dysplastic and non-dysplastic femoroacetabular impingement (FAI) hips, the relationship of acetabular and femoral version (FV) within dysplastic hips and the contribution of each of these factors to symptoms and outcomes of dysplasia treatment. We sought to describe the acetabular version (AcetV) and FV in dysplastic hips and quantify how these measurements compared with non-dysplastic FAI hips. We also sought to analyze the association of these factors with patient-reported outcomes (PROs) after periacetabular osteotomy (PAO) and determine the need for subsequent femoral derotational osteotomy after PAO. A total of 113 dysplastic patients who underwent PAO (92% female, mean age 24) were compared with 1332 (45% female, mean age 25) non-dysplastic FAI (CEA > 25°) patients. We found that dysplastic hips had a statistically higher AcetV and FV than non-dysplastic FAI hips. There was a very weak correlation between AcetV and FV in dysplastic hips, suggesting that patients with higher AcetV did not necessarily have higher FV. There was no association with AcetV or FV and patient outcomes in our very limited analysis of PROs after PAO, and only 5% of patients with excessive FV (>20°) required subsequent femoral derotational osteotomy, suggesting that in a majority of patients with hip dysplasia, FV may not impact the post-operative clinical course.

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.

Femoroacetabular Impingement: A Natural History

This review article is devoted to the natural course of hip femoroacetabular impingement (FAI). The evolution of the understanding and views of surgeons on primary (idiopathic) arthrosis are considered. It is noted that nowadays, the primary arthrosis in fact almost always arises from anatomical variations. Among those are cam- and pincer-deformities, leading to impingement. In most of the major works, a reliable causal relationship of cam-FAI with arthrosis has been proven. Moreover, cam-FAI also carries the risk of impending arthroplasty. The association of pincer-FAI with arthrosis has been controversial. The course of FAI arthrosis, most likely, is not as aggressive as, for example, dysplastic arthrosis, and less often requires arthroplastics. Since cam-FAI is a reliable risk factor for arthrosis and arthroplasty, it could be assumed that timely surgical correction of FAI would stop or slow down arthrosis and avoid arthroplasty. However, at present, this assumption has not been proven, therefore, there is no reason to assert that surgery for FAI in any way affects its natural history in the form of severe arthrosis following by arthroplasty.