Doctor of Philosophy

dissertationAltered mechanics are believed to initiate osteoarthritis in hips with acetabular dysplasia. Periacetabular osteotomy (PAO) is the preferred surgical treatment; however, it is unknown if the procedure normalizes joint anatomy and mechanics. Changes in three-dimensional (3D) morphology and chondrolabral mechanics were quantified after PAO. Finite element (FE) models demonstrated that PAO improved the distribution of coverage, reduced stress, increased congruity, and prevented cartilage thinning. However, changes in mechanics were not consistent. In fact, one patient exhibited increased stress after surgery, which was believed to be a result of over-correction. Therefore, methods to integrate morphologic and biomechanical analysis with clinical care could standardize outcomes of PAO. FE simulations are time-intensive and require significant computing resources. Therefore, the second aim was to implement an efficient method to estimate mechanics. An enhanced discrete element analysis (DEA) model of the hip that accurately incorporated cartilage geometry and efficiently calculated stress was developed and analyzed. Although DEA model estimates predicted elevated magnitudes of contact stress, the distribution corresponded well with FE models. As a computationally efficient platform, DEA could assist in diagnosis and surgical planning. Imaging is a precursor to analyzing morphology and biomechanics. Ideally, an imaging protocol would visualize bone and soft-tissue at high resolution without ionizing radiation. Magnetic resonance imaging (MRI) with 3D dual-echo-steady-state (DESS) is a promising sequence to image the hip noninvasively, but its accuracy has not been quantified. Therefore, the final aim was to implement and validate the use of 3D DESS MRI in the hip. Using direct measurements of cartilage thickness as the standard, 3D DESS MRI imaged cartilage to ~0.5 mm of the physical measurements with 95% confidence, which is comparable to the most accurate hip imaging protocol presented to date. In summary, this dissertation provided unique insights into the morphologic and biomechanical features following PAO. In the future, DEA could be combined with 3D DESS MRI to efficiently analyze contact stress distributions. These methods could be incorporated into preoperative planning software, where the algorithm would predict the optimal relocation of the acetabulum to maximize femoral head coverage while minimizing contact stress, and thereby improve long-term outcomes of PAO

Viability and tissue quality of cartilage flaps from patients with femoroacetabular hip impingement: A matched-control comparison

Background: Chondrolabral damage is commonly observed in patients with cam-type femoroacetabular impingement (FAI). Chondral flap reattachment has recently been proposed as a possible preservation technique. Purpose/Hypothesis: The purpose of this study was to determine the viability and tissue quality of chondral flaps from patients with FAI at the time of arthroscopy. It was hypothesized that chondral flaps from patients with cam lesions of the hip would exhibit less viability and greater tissue degeneration than would those of a matched control group. Study Design: Cohort study; Level of evidence, 2. Methods: Patients with cam-type FAI who were treated with hip arthroscopy between 2014 and 2016 were asked to participate in this study. The cartilage lesions were localized and classified intraoperatively according to Beck classification. A chondral flap (study group) and a cartilage sample (control group) were obtained from each patient for histologic evaluation. Cellular viability and tissue quality were examined and compared in both groups. Cellular viability was determined with live/dead staining, and tissue quality was evaluated using safranin O/fast green, hematoxylin and eosin (H&amp;E) staining, and immunohistochemistry for collagen II. Osteoarthritis Research Society International (OARSI) grading was used for quality assessment, and Image J software was used to calculate the percentage of tissue viability and Col II stain. Results: A total of 10 male patients with a mean age of 38.4 years (range, 30-55 years) were enrolled. All chondral flaps were classified as Beck grade 4. The mean cellular viability of the chondral flaps was reduced (54.6% ± 25.6%), and they were found to be degenerated (OARSI grade, 4 ± 1.27). Control samples also had reduced viability (38.8% ± 30.3%) and were degenerative (OARSI grade, 3.5 ± 1.38). There was no statistically significant intergroup difference for viability ( P = .203) or OARSI grade ( P = .645), nor was there an intragroup correlation between viability and OARSI grade ( P &gt; .05). A significant negative correlation ( r = −0.9, P = .035) was found between OARSI grade and collagen II percentage scale in 5 selected samples. Conclusion: Despite appearing normal macroscopically, the chondral flaps from patients with cam-type FAI displayed loss of viability and tissue degeneration. In addition, control samples obtained away from the injury area also displayed cartilage damage and degeneration. Careful consideration should be taken when attempting to reattach the chondral flap. </jats:sec

寛骨臼回転骨切り術後における臼蓋窩線維軟骨形成－関連因子と臨床成績の評価

福岡大学201

Doctor of Philosophy

dissertationWhile the healthy hip provides decades of pain free articulation, the cartilage and labrum may degenerate during the process of osteoarthritis (OA). Most hip OA is caused by subtle pathomorphologies, including acetabular dysplasia and acetabular retroversion. The link between pathomorphology and OA is thought to be mechanical, but the mechanics have not been quantified. The aim of this dissertation was to provide insight into the pathogenesis of hip OA via finite element (FE) modeling. The objectives were two-fold: to validate a subject-specific modeling protocol for a series of specimens and assess the effects of assumptions on model predictions, and to use the modeling protocol to evaluate soft tissue mechanics in pathomorphologic hips in comparison to normal hips. For the first objective, FE predictions of contact stress and contact area were directly validated for five cadaveric specimens, and the specimen- and region-specific hyperelastic material behavior of cartilage was determined. FE predictions of contact stress and contact area were in good agreement with experimental results, and were relatively insensitive to the assumed cartilage constitutive model. There were distinct regional differences in the hyperelastic material behavior of human hip cartilage, with stiffer lateral than medial cartilage and stiffer acetabular than femoral cartilage. In order to investigate the mechanical link between pathomorphology and hip OA, FE models of ten hips with normal morphology, ten hips with acetabular dysplasia and ten hips with acetabular retroversion were generated. FE models of dysplastic acetabula demonstrated the importance of the acetabular labrum in load support in the dysplastic hip. FE models of retroverted acetabula demonstrated distinct superomedial contact patterns in comparison to distributed contact patterns in the normal hip. Finally, the effects of cartilage constitutive model on predictions of transchondral maximum shear stress and first principal strain were evaluated. In contrast to contact stress and contact area, maximum shear stress and first principal strain were sensitive to the cartilage constitutive model. Overall, this dissertation provides novel insights into the contact mechanics of pathomorphologic hips that may be important in the pathogenesis of OA, as well as the technical foundation for studies evaluating additional mechanical variables in the human hip

ARTHROSCOPIC TREATMENT OF FEMOROACETABULAR IMPINGEMENT

ABSTRACTObjective: The purpose of this study is to evaluate the short-term follow-up results of arthroscopic treatment of femoroacetabular impingement. Our hypothesis is that arthroscopic treatment results are favorable. Methods: Between August 2003 and August 2007, 28 hips had femoroacetabular impingement treated by hip arthroscopy. The mean age was 34 years, with mean follow-up period of 27 months. Clinical results were graded with the modified Harris hip score, which was measured pre- and postoperatively. Patients had also their internal rotation analyzed. These parameters were calculated by using Wilcoxon's t test for analysis of nonparametric paired samples performed. Results: The mean preoperative Harris Hip Score was 54.2, improving to 94.8 postoperatively (p<0,001). The mean increase was 37.5 points. We had 4 good results (15%) and 24 excellent results (85%). Preoperatively, the patients had a mean internal rotation of 17°, and, postoperatively, 36°. The average internal rotation increase was 19° (p<0,001). Conclusions: The arthroscopic treatment of femoroacetabular impingement presents satisfactory results

Doctor of Philosophy

dissertationGeometric abnormalities of the human hip joint, as found in femoroacetabular impingement (FAI) and acetabular dysplasia, alter hip biomechanics and may be the primary causes of osteoarthritis in young adults. However, empirical evidence of direct correlations between abnormal geometry, altered biomechanics, and osteoarthritis is scarce. Also, clinical measures used to diagnose FAI and dysplasia still have substantial limitations, including questions about their reliability, assumptions about hip joint geometry and their ability to definitively distinguish pathologic from normal hips. The goals of this dissertation are twofold. First, a set of tools are presented and applied to quantify three-dimensional (3D) anatomical differences between hips with FAI and control subjects. The 3D tools were developed, validated and applied to patients with a subtype of FAI, called cam FAI, to improve basic understanding of the spectrum of FAI deformities, and to provide meaningful new metrics of morphology that are relatable to current diagnostic methods and translate easily for clinical use. The second goal of this dissertation is to improve our understanding of intra-articular hip contact mechanics as well as hip joint kinematics and muscle forces. To do so, a finite element study of intraarticular cartilage contact mechanics was completed with a cohort of live human subjects, using a validated modeling protocol. Finally, musculoskeletal modeling was used with gait data from healthy subjects and acetabular dysplasia patients to provide preliminary estimates of hip joint kinematics, kinetics, and muscle forces and compare differences between the groups. The translational methods of this dissertation utilized techniques from orthopaedics, computer science, physical therapy, mechanics, and medical imaging. Results from this dissertation offer new insight into the complex pathomechanics and pathomorphology of FAI and acetabular dysplasia. Application and extension of the work of this dissertation has the potential to help establish links between FAI and dysplasia with osteoarthritis and to improve patient care

Biphasic bone graft substitute in revision total hip arthroplasty with significant acetabular bone defects : a retrospective analysis.

AIMS: Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. METHODS: We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures. RESULTS: Mean follow-up was 39.5 months (36 to 71), with a significant improvement in post-revision function compared to preoperative function. Graft site remodelling was rated radiologically as moderate in 31 hips (63%) and strong in 12 hips (24%). There were no cases of complete graft site dissolution. No acetabular loosening was identified. None of the patients developed clinically significant heterotopic ossification. There were twelve reoperations: six patients developed post-revision infections, three experienced dislocations, two sustained periprosthetic femur fractures, and one subject had femoral component aseptic loosening. CONCLUSION: Our series reports bone defect restoration with the sole use of a biphasic injectable BGS in the periacetabular region. We did not observe significant graft dissolution. We emphasize that successful graft site remodelling requires meticulous recipient site preparation.Cite this article: Bone Jt Open&nbsp;2022;3(12):991-997

Total hip arthroplasty, osteolysis and cardiovascular disease in patients with osteoarthritis of the hip

The pathogenesis of OA and CVD is currently related to inflammatory processes. It is unknown how OA and its surgical treatment impact the cardiovascular system. Hypotheses We hypothesized that (1) THA patients more than 5 years after the index surgery have an increased risk for cardiovascular morbidity and mortality compared with the general population and (2) that late cardiovascular risk following THA may be mediated by the development of osteolysis and systemic inflammation. Furthermore, we hypothesized that patients with asymptomatic osteolysis after THA (3) are more likely to develop CVD and (4) have a higher burden of cardiovascular risk markers than patients without periacetabular osteolysis. Aims of the studies The general aim of this thesis was to investigate patients treated with THA due to OA and patients treated with THA who subsequently underwent revision surgery and the associated risk of cardiovascular morbidity and mortality. Further aims were to compare patients with and without periacetabular osteolysis regarding CVD and cardiovascular risk markers. The specific aims were as follows: Paper I: to determine whether there is a late correlation between THA and cardiovascular events. Paper II: to compare patients after revision surgery due to aseptic loosening of the implant to controls (patients not having revision surgery) regarding the risk for cardiovascular morbidity and mortality and the time to first event during the exposure period. Paper III: to investigate whether THA patients with asymptomatic periacetabular osteolysis have an increased long-term risk of CVD compared to THA patients without osteolysis and the time to event. Paper IV: to compare THA patients with and without periacetabular osteolysis regarding cardiovascular risk markers and electrocardiography findings. Materials and methods/results Paper I: This was a nationwide, matched cohort study with data on 91,527 OA patients who underwent surgical treatment. Data were obtained from the Swedish Hip Arthroplasty Register. A control cohort consisting of 270,688 patients from the general Swedish population was matched at a ratio of 1:3 to each case by sex, age, and residence. The mean follow-up time was 10 years. Patients with surgically treated OA of the hip had an increased risk of cardiovascular morbidity and mortality many years after the operation compared with controls. Paper II: This was a nationwide, nested, case-control study consisting of 14,430 patients undergoing cemented THA due to OA between the years 1992 and 2005. The case group consisted of 2,886 patients who underwent reoperation on the treated hip due to osteolysis or aseptic loosening at any time within five years after the index surgery. Each case was matched with four controls (11,544). Patients with OA who underwent THA and subsequently underwent revision surgery due to loosening had a higher risk of developing cardiovascular events than controls. Paper III: This was an observational cohort study of 139 patients who underwent uncemented THA between 1992 and 2007. All patients were assessed by CT of the affected hip to sort patients into 2 groups, those with periacetabular osteolysis (cases=33) and those without periacetabular osteolysis (controls=106). There was a higher rate of CVD among THA patients with periacetabular osteolysis than among THA patients without periacetabular osteolysis but no statistically significant risk increase. Paper IV: This was a cross-sectional study consisting of 108 patients who underwent THA (uncemented components) due to OA between 1992 and 2007. All patients were assessed by CT of the affected hip. Patients with periacetabular osteolysis constituted the cases (n=19) patients without periacetabular osteolysis (n=89) were selected as controls.(89) Markers of inflammation, risk markers for CVD and ECG abnormalities were collected and compared between the groups. There was no difference in the risk burden for CVD many years after THA between patients with and without periacetabular osteolysis. Conclusions: Patients with surgically treated OA of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation. Patients who undergo revision surgery due to aseptic loosening and/or osteolysis have a higher risk of developing cardiovascular events. These observations may be indicative of common disease pathways. Furthermore, while the risk for CVD in patients with periacetabular osteolysis is slightly higher, there is no significant difference in the risk burden for CVD compared with patients without periacetabular osteolysis. The examination of a larger sample and the use of comparable durations after surgery are recommended

Pathobiological analysis of developmental dysplasia of the hip and its progression to osteoarthritis

Developmental dysplasia of the hip (DDH) is recognized as one of the leading causes of early-onset hip osteoarthritis and a primary reason for undergoing total hip arthroplasty prior to 50 years of age. Even with an increase in awareness and focus on infant screening and early diagnosis, approximately 15-25 percent of DDH cases remain undiagnosed into early adulthood when prevention is no longer possible, interventions are more invasive, and joint degeneration has begun. To improve screening and early diagnosis methods for DDH, the pathobiological mechanisms associated with this disorder must be further characterized. Therefore, the programmatic research plan for this dissertation investigated molecular biology, mechanobiology, biomechanics, and cell- and tissue-based disease mechanisms associated with DDH during its development and progression to secondary hip osteoarthritis. The primary objective for this body of work was to comprehensively characterize these stages of DDH in order to elucidate mechanistic biomarkers for diagnosis, staging, and treatment monitoring as well as targets for novel prevention and treatment strategies. The first experiment in the dissertation research focused on clinically relevant biomechanics of the hip in order to characterize the relevant contributions from key soft tissue structures in maintaining hip stability. The data from this experiment indicated that the ligamentum teres of the femoral head and the acetabular labrum each play important and unique roles in hip joint stability. The ligamentum teres primarily supported anterior stability during increased hip flexion while the labrum primarily supported lateral stability during hip flexion and abduction. The second set of experiments focused on the molecular biology of key intra-articular tissues of the hip by analyzing mechanistic metabolic responses in cell and tissue culture. First, metabolic responses related to hip osteoarthritis were characterized and analyzed for trends with histopathology severity scoring. The results indicated that each tissue type has a unique metabolic profile. Interestingly, the acetabular labrum was associated with robust inflammatory, degradative, immune cell recruitment, and anabolic responses during early degeneration followed by a pronounced anti-degradative response in late degeneration. Subsequent experiments used cells from canine DDH tissues to investigate mechanobiology-related responses prior to the onset of hip osteoarthritis. The results indicated that the ligamentum teres is a primary producer of inflammatory and immune cell recruitment proteins with labral cells also producing significant amounts of these proteins in response to supraphysiologic tensile loading. Interestingly, physiologic loading of dysplastic cells normalized their metabolic response profiles to match those of healthy hips, indicating that dysplastic metabolic responses can be reversible in earlier stages of disease. The final set of experiments for the dissertation focused on analysis of serum and urine from age-matched healthy individuals and those with symptomatic DDH prior to degeneration in order to elucidate mechanistic biomarker panels for differentiating hip status prior to the development of osteoarthritis. Patients with DDH prior to degeneration had significantly different serum and urine biomarker profiles compared to healthy-hip controls and patients with hip osteoarthritis. The primary differences involved increases in inflammatory biomarkers and decreases in bone metabolism, degradation, and anabolism biomarkers. When these proteins were combined into panels, there was excellent discriminatory capability for multiple serum and urine protein panels. Taken together, this series of experiments provides novel molecular biology, mechanobiology, biomechanics, and cell- and tissue-based disease mechanisms data for characterizing DDH during its development and progression to secondary hip osteoarthritis. These data suggest that soft tissue structures in the hip, including the ligamentum teres and acetabular labrum, play key biomechanical and biologic roles in maintaining joint homeostasis and responding to the pathomechanisms involved in the development and progression of DDH. The experiments comprising this dissertation provide the foundation for additional translational and clinical studies designed to comprehensively characterize DDH development and progression and elucidate mechanistic biomarkers that can consistently identify individuals with hip dysplasia at its earliest stages such that progression to hip osteoarthritis can be prevented.Includes bibliographical references

Osteoarthritis of the Hip Joint

The incidence of osteoarthritis of the hip is increasing internationally. With the population becoming older and the rates of obesity increasing on a global scale, we are seeing more traumatic and idiopathic degeneration of the native hip joint. The pathological processes occurring in the hip have been described at a macroscopic and microscopic level. The inability of surface hyaline cartilage to heal is one of the major contributors to the irreversible nature of degeneration once it begins. Many classification systems have been described to characterise the extent of disease. History and examination play a pivotal role in the management algorithm. The goals of treatment are to improve pain, function and quality of life. Numerous non-operative treatments exist as do many operative interventions. Total hip arthroplasty is arguably the most successful operation developed in orthopaedic surgery to date. We discuss the condition of osteoarthritis as it pertains to the hip and we consider the patients’ course from onset of symptoms through their investigation up to their definitive management