The diagnosis and treatment of hip disease in young adults has rapidly evolved over the past ten years. Despite the advancements of improved diagnostic skills and refinement of surgical techniques, the psychosocial impact hip disease has on the young adult has not yet been elucidated. This observational study aimed to characterise the functional and psychosocial characteristics of a group of patients from our young hip clinic. 49 patients responded to a postal questionnaire which included the Oswestry Disability Index (ODI) and Hospital Anxiety and Depression Scale (HADS). Median age was 20 years (range 16-38) with a gender ratio of 2:1 (female: male). The most common diagnoses were Perthes' disease and developmental hip dysplasia. More than half of our patients had moderate to severe pain based on the Visual Analogue Scale (VAS) and at least a moderate disability based on the ODI. Thirty-two percent of patients were classified as having borderline to abnormal levels of depression and 49% of patients were classified as having borderline to abnormal levels of anxiety based on the HADS. Comparison of the ODI with the VAS and HADS anxiety and depression subscales showed a significant positive correlation (p<0.05). Multiple regression showed the ODI to be a significant predictor of the HADS anxiety and depression scores (regression coefficient 0.13, 95% confidence interval 0.06 to 0.21, p<0.05). This study highlights the previously unrecognised psychosocial effects of hip disease in the young adult. A questionnaire which includes HADS may be of particular value in screening for depression and anxiety in young people with physical illness. This study also highlights that collaboration with psychologists and other health care providers may be required to achieve a multidisciplinary approach in managing these patients

The modified Hedgehog technique was previously used to reattach pure chondral shear-off fragments in the pediatric knee. In the modified Hedgehog technique, the calcified side of chondral fragments is multiple times incised and trimmed obliquely for an interlocking fit in the defect site. Fibrin glue with or without sutures is subsequently applied to fix the fragment to the defect. This preliminary report further elucidates the potential of the technique by evaluation of its application in young adults using patient reported outcome measures (PROMs) and high-field Magnetic Resonance Imaging (MRI) as outcome measures. Three patients with a femoral cartilage defect (2 medial, 1 lateral), and a concomitant pure chondral corpus liberum were operatively treated by the modified Hedgehog technique. Age at surgery ranged from 20.6–21.2 years, defect size ranged from 3.8–6.0 cm2. Patients were evaluated at three months and one year after surgery by PROMs and 7.0T MRI. PROMs included the Internation Knee Documentation (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale (VAS) questionnaires. 7.0T MRI (Magnetom, Siemens Healthcare, Erlangen, Germany) using a 28-channel proton knee coil (QED, Electrodynamics LLC, Cleveland, OH) included a proton density weighted turbo spin-echo sequence with fat suppression to assess morphological tissue structure andgagCEST imaging to measure the biochemical tissue composition in terms of glycosaminoglycans (GAG). Twelve months after surgery all patients reported no pain and showed full range of motion. While PROMs at three months showed large variability between patients, one year after surgery the scores were consistently improved. Over time, morphological MRI visualized improvements in integration of the cartilage fragment with the surrounding cartilage, which was supported by biochemical MRI showing increased GAG values at the defect edges. Statistics were not applied to the results because of the small sample size. The modified Hedgehog technique in young adults with an acute onset caused by a pure chondral corpus liberum can be considered promising. The improved PROM results over time were supported by 7.0T MRI that visualized improvements in tissue structure and biochemical composition. Inclusion of more patients in future studies would allow statistical analysis and more conclusive results. The etiology of loosening and time between onset of symptoms and surgery for successful graft integration may differ between pediatric and young adult patients and is subject for future studies

Primary malignant bone and soft tissue tumours often occur in the lower extremities of active individuals including children, teenagers and young adults. Survivors routinely face long-term physical disability. Participation in sports is particularly important for active young people but the impact of sarcoma treatment is not widely recognised and clinicians may be unable to provide objective advice about returning to sports. We aimed to identify and summarise the current evidence for involvement in sports following treatment of lower limb primary malignant bone and soft tissue tumours. A comprehensive search strategy was used to identify relevant studies combining the main concepts of interest: (1) Bone/Soft Tissue Tumour, (2) Lower Limb, (3) Surgical Interventions and (4) Sports. Studies were selected according to eligibility criteria with the consensus of three authors. Customised data extraction and quality assessment tools were used. 22 studies were selected, published between 1985 – 2020, and comprising 1005 patients. Fifteen studies with data on return to sports including 705 participants of which 412 (58.4%) returned to some form of sport at a mean follow-up period of 7.6 years. Four studies directly compared limb sparing and amputation; none of these were able to identify a difference in sports participation or ability. Return to sports is important for patients treated for musculoskeletal tumours, however, there is insufficient published research to provide good information and support for patients. Future prospective studies are needed to collect better pre and post-treatment data at multiple time intervals and validated clinical and patient sports participation outcomes such as type of sports participation, level and frequency and a validated sports specific outcome score, such as UCLA assessment. In particular, more comparison between limb sparing and amputation would be welcome

Introduction. The most frequent diagnosis in young adults undergoing total hip arthroplasty (THA) is osteonecrosis of the femoral head (ONFH), an evolving and disabling condition with an increasing prevalence worldwide. Treatment of ONFH remains a challenge mainly because of a lack of understanding of the disease's pathophysiological basis. This study investigated the biological processes that could be affected by ONFH by comparing the microstructure, histological characteristics and transcriptomic profile of trabecular bone from the femoral head (FH) and the intertrochanteric region (IT) of patients suffering from this condition. Method. A total of 18 patients with idiopathic ONFH undergoing THA in our institution were included. Trabecular bone explants were taken intraoperatively from the FH and the IT of patients. Bone microstructure was examined by micro-computed tomography (micro-CT). After bone sectioning, histological features were studied by hematoxylin and eosin staining. Differential gene expression was investigated using a microarray platform. Result. Micro-CT imaging showed higher trabecular separation and lower trabecular thickness and bone volume in trabecular bone from the FH than from the IT. Histological staining revealed that the number of osteoblasts on the bone surface and the percentage of empty lacunae were higher in trabecular bone from the FH. Transcriptome analysis identified a differential signature in trabecular bone from the FH compared to the IT. The gene ontology analyses of the genes overexpressed in trabecular bone from the FH revealed a range of enriched biological processes related to cell division and immune response. In contrast, most downregulated transcripts were involved in bone formation. Conclusion. This study identified changes in the microarchitecture, histological features and transcriptomic signature of trabecular bone from the FH of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. This work was supported by PI22/00939 grant from ISCIII-FEDER-MICINN-AES and Luis Alvarez grant from IdiPAZ

Management of ankle arthritis in young patients is challenging. Although ankle arthrodesis gives consistent pain relief, it leads to loss of function and adjacent joint arthritis. Ankle joint distraction (AJD) has been shown to give good outcomes in adults with osteoarthritis or post-traumatic arthritis. The efficacy in children or young adults and those with juvenile idiopathic arthritis is less well evidenced. Clinical notes and radiographs of all patients (n=6) managed with AJD in one tertiary referral centre were retrospectively reviewed. Radiographs were taken pre-surgery, intra-operatively, 1 month following frame removal and at the last follow up, tibiotalar joint space was assessed using ImageJ software. Measurements were taken at the medial, middle and lateral talar dome using frame components as reference. Radiographic data for patients with a good clinical outcome was compared with those who did not. At time of surgery mean age was 16.1 years (12 – 25 years). Mean follow up was 3.4 years (1.5 – 5.9 years). Indications were juvenile idiopathic arthritis (4) post-traumatic (1) and post-infective arthritis (1). Three patients at last follow up had a good clinical outcome. Two patients required revision to arthrodesis (1.3 and 2.4 years following distraction). One patient had spontaneous fusion. One patient required oral antibiotics for pin site infection. Inter-observer reliability was 95%. Mean joint space was 1.17mm (SD = 0.87mm) pre-operatively which increased to 6.72mm (SD = 2.23mm) at the time of distraction and 2.09mm (SD = 1.14mm) at the time of removal. At one-year follow up, mean joint space was 1.96mm (SD = 1.97mm). Outcomes following AJD in this population are variable although significant benefits were demonstrated for 50% of the patients in this series. Radiographic joint space preoperatively did not appear to be associated with need for arthrodesis. Further research in larger groups of young patients is required

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model. Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05. When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice. Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis

Objectives. Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. Methods. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts. Results. MSCs from OVX rats migrate significantly (p < 0.05) less towards SDF-1 (9%, . sd. 5%) compared with MSCs from adult (15%, . sd. 3%) and young rats (25%, . sd. 4%). Cells transfected with CXCR4 migrated significantly more towards SDF-1 compared with non-transfected cells, irrespective of whether these cells were from OVX (26.5%, . sd. 4%), young (47%, . sd. 17%) or adult (21%, . sd. 4%) rats. Transfected MSCs differentiated to osteoblasts express CXCR4 but do not migrate towards SDF-1. Conclusions. MSC migration is impaired by age and osteoporosis in rats, and this may be associated with a significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by upregulating CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients. Cite this article: A. Sanghani-Kerai, M. Coathup, S. Samazideh, P. Kalia, L. Di Silvio, B. Idowu, G. Blunn. Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4. Bone Joint Res 2017;6:–365. DOI: 10.1302/2046-3758.66.BJR-2016-0259.R1

Hip Osteoarthritis (HOA) is the most common joint disorder and a major cause of disability in the adult population, leading to total hip replacement (THR). Recently, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early OA in the non-dysplastic hip. FAI is a pathological mechanical process, caused by abnormalities of the acetabulum and/or femur leading to damage the soft tissue structures. FAI can determine chondro-labral damage and groin pain in young adults and can accelerate HOA progression in middle-aged adults. The aim of the study was to determine if the presence of calcium crystal in synovial fluid (SF) at the time of FAI surgery affects the clinical outcomes to be used as diagnostic and predictive biomarker. 49 patients with FAI undergoing arthroscopy were enrolled after providing informed consent; 37 SFs were collected by arthrocentesis at the time of surgery and 35 analyzed (66% males), median age 35 years with standard deviation (SD) 9.7 and body mass index (BMI) 23.4 kg/m. 2. ; e SD 3. At the time of surgery, chondral pathology using the Outerbridge score, labral pathology and macroscopic synovial pathology based on direct arthroscopic visualization were evaluated. Physical examination and clinical assessment using the Hip disability & Osteoarthritis Outcome Score (HOOS) were performed at the time of surgery and at 6 months of follow up. As positive controls of OA signs, SF samples were also collected from cohort of 15 patients with HOA undergoing THR and 12 were analysed. 45% FAI patients showed CAM deformity; 88% presented labral lesion or instability and 68% radiographic labral calcification. 4 patients out of 35 showed moderate radiographic signs of OA (Kellegren-Lawrence score = 3). Pre-operative HOOS median value was 61.3% (68.10-40.03) with interquartile range (IQR) of 75-25% and post-operative HOOS median value 90% with IQR 93.8-80.60. In both FAI and OA patients the calcium crystal level in SFs negatively correlated with glycosaminoglycan (component of the extracellular matrix) released, which is a marker of cartilage damage (Spearman rho=-0.601, p<0.001). In FAI patients a worst articular function after surgery, measured with the HOOS questionnaire, was associated with both acetabular and femoral chondropathy and degenerative labral lesion. Moreover, radiographic labral calcification was also significantly associated with pain, worst articular function and labral lesion. Calcium crystal level in SFs was associated with labral lesions and OA signs. We concluded that the levels of calcium crystals in FAI patients are correlated with joint damage, OA signs and worst post-operative outcome. The presence of calcium crystals in SF of FAI patients might be a potential new biomarker that might help clinicians to make an early diagnosis, evaluate disease progression and monitor treatment response

Introduction. A deep squat (DS) is a challenging motion at the level of the hip joint generating substantial reaction forces (HJRF). During DS, the hip flexion angle approximates the functional range of hip motion. In some hip morphologies this femoroacetabular conflict has been shown to occur as early as 80° of hip flexion. So far in-vivo HJRF measurements have been limited to instrumented hip implants in a limited number of older patients performing incomplete squats (< 50° hip flexion and < 80° knee flexion). Clearly, young adults have a different kinetical profile with hip and knee flexion ranges going well over 100 degrees. Since hip loading data on this subgroup of the population is lacking and performing invasive measurements would be unfeasible, this study aimed to report a personalised numerical model solution based on inverse dynamics to calculate realistic in silico HJRF values during DS. M&M. Fifty athletic males (18–25 years old) were prospectively recruited for motion and morphological analysis. DS motion capture (MoCap) acquisitions and MRI scans of the lower extremities with gait lab marker positions were obtained. The AnyBody Modelling System (v6.1.1) was used to implement a novel personalisation workflow of the AnyMoCap template model. Bone geometries, semi-automatically segmented from MRI, and corresponding markers were incorporated into the template human model by an automated nonlinear morphing. Furthermore, a state-of-the-art TLEM 2.0 dataset, included in the Anybody Managed Model Repository (v2.0), was used in the template model. The subject-specific MoCap trials were processed to compute squat motion by resolving an overdeterminate kinematics problem. Inverse dynamics analyses were carried out to compute muscle and joint reaction forces in the entire body. Resulting hip joint loads were validated with measured in-vivo data from Knee bend trials in the OrthoLoad library. Additionally, anterior pelvic tilt, hip and knee joint angles were computed. Results. A preliminary set of results (20 out of 50 subjects) was analysed. The average HJRF was 3.42 times bodyweight at the peak of DS (95% confidence interval: 2.99 – 3.85%BW). Maximal hip and knee flexion angles were 113° (109.7°–116.8°) and 116° (109.4 – 123.0°) respectively. The anterior pelvic tilt demonstrated a biphasic profile with peak value of 33° (28.1° – 38.4°). Discussion. A non-invasive and highly personalised alternative for determining hip loading was presented. Consistently higher HJR forces during DS in young adults were demonstrated as opposed to the Orthoload dataset. Similarly, knee and hip flexion angles were much higher, which could support the increase in HJRF. We can conclude that DS hip kinetics in young adults clearly differ from the typical total hip arthroplasty population

Introduction and Objective. Ankle fractures are common and affect young adults as well as the elderly. An unstable ankle fracture treatment typically involves surgical fixation, immobilisation, and modified weight-bearing for six weeks. Non-weight bearing (NWB) cast immobilisation periods were used to protect the soft tissue envelope and osteosynthesis. This can have implications on patient function and may reduce independence, mobility and return to work. Newer trends in earlier mobilisation compete with traditional NWB doctrine, and weak consensus exists as to the best postoperative strategy. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion (ROM) exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates. Materials and Methods. A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus non-weight-bearing (NWB) and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures (lateral malleolar, bimalleolar, trimalleolar with or without syndesmotic injury). The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection (deep and superficial), displacement of osteosynthesis, the full arc of ankle motion (plantar flexion and dorsal flection), RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay. Results. We recruited 160 patients with an unstable ankle fracture. Participants’ ages ranged from 15 to 94 years (M = 45.5, SD = 17.2), with 54% identified as female. The mean time from injury to surgical fixation was 1.3 days (0 to 17 days). Patients in the immediate weight-bearing group had a 9.5-point higher mean OMAS at six weeks postoperatively (95% CI 1.48, 17.52) P = 0.021. The complications rate was similar in both groups. The rate of surgical site infection was 4.3%. One patient had DVT, and another patient had a pulmonary embolism; both were randomised to NWB. Length of hospital stay (LOS) was 1 ± 1.5 (0, 12) for the IWB group vs 1.5 ± 2.5 (0, 19) for the NWB group. Conclusions. There is a paucity of quality evidence supporting the postoperative management regimes used most commonly in clinical practice. To our knowledge, immediate weight-bearing (IWB) following ORIF of all types of unstable ankle fractures has not been investigated in a controlled prospective manner in recent decades. In this large multicentre, randomised controlled trial, we investigated immediate weight-bearing following ORIF of all ankle fracture patterns in the usual care condition using standard fixation methods. Our result suggests that IWB following ankle fracture fixation is safe and resulted in a better functional outcome. Once anatomical reduction and stable internal fixation is achieved, we recommend IWB in all types of ankle fractures in a compliant patient

There is increasing interest in using anabolic factors such as stem cells to augment fragility fracture repair. One of the factors associated with fracture healing is the retention and migration of stem cells to the site of injury (1–3). The aim of this study was to isolate stem cells from osteopenic rats and investigate and compare the CD marker expression, proliferation, migration, osteogenic and adipogenic differentiation. The hypothesis of this study is that the migration of MSCs from young, adult and ovariectomised (OVX) rats will have different proliferation, differentiation and migratory abilities. CD marker expression of MSCs from young, adult and osteopenic rats was measured using flow cytometry. Proliferation, osteogenic differentiation and adipogenic differentiation was measured using Alamar Blue, ALP expression and Alizari n Red and quantitative Oil red O respectively. Cells were incubated in Boyden chambers to quantify their migration towards SDF1. Data was analysed using a Student t-test where p values < 0.05 were considered significant. MSCs from all 3 groups of rats had similar proliferation and expression of CD29(>90%), CD90(>96%), CD34(<5%) and CD45(approx 10%). The proliferation rate was also similar. However, interestingly the migration and differentiation ability was significantly different between the MSCs from the 3 groups of rats. The young MSCs were not only better at differentiating into bone and fat, but they also migrated significantly more towards SDF1. MSCs from OVX rats are similar to MSCs from young rats. However when induced to turn into bone, fat and migrate towards SDF1, young MSCs are significantly more responsive than MSCs from OVX and adult control rats. The poor homing ability and differentiation of the stem cells and their retention may result in a reduction in bone formation leading to delayed union in fractures of osteoporotic patients(4)

The current treatment for osteoporosis such as bisphosphonates inhibits the catabolic activity of osteoclasts and subsequent bone resorption, but does not increase bone formation. There is therefore interest in using anabolic factors such as stem cells to augment fracture repair. The poor bone formation in postmenopausal women could be due to poor retention and function of Mesenchymal stem cells (MSCs) resulting into delayed unions. Another factor associated with fracture healing is the retention and migration of stem cells to the site of injury (1–3). The aim of this study was to isolate stem cells from osteopenic rats and investigate and compare the CD marker expression, proliferation, migration, osteogenic and adipogenic differentiation. The hypothesis of this study is that the migration of MSCs from young, adult and ovariectomised (OVX) rats will have different proliferation, differentiation and migratory abilities. Ovariectomy was performed in 6–9 month old Wistar rats and osteopenia developed over a 4 month post-op period. MSCs were harvested from the femora of young, adult and osteopenic Wistar rats. Proliferation of the these MSCs from the three group of rats was measured using Alamar blue, osteogenic differentiation was measured using ALP expression at day 0, 7, 14 and 21 and alizarin red at day 21. Adipogenic differentiation was measured at day 7, 14 and 21 using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF1. For analysis, the number of cells migrating across the membrane was expressed as a percentage of the cells remaining on the upper membrane surface. Data was analysed using a Student t-test where p values < 0.05 were considered significant. The stem cells from all 3 groups of rats expressed on average the same amount of CD29 (>90%), CD90 (>96%), CD34 (<5%) and CD45 (approx 10%). The proliferation rate measured by Alamar blue normalised against DNA was also similar at day 3, 7, 10 and 14. However, interestingly the migration and differentiation ability was significantly different between the MSCs from the 3 groups of rats. The young MSCs were not only better at differentiating into bone and fat as well, but they also migrated significantly more towards SDF1. The migration of SDF-1 doubled with young rats compared to the adult rats (p = 0.023) and it was four times higher when compared to cells isolated from OVX rats (p = 0.013). MSCs from OVX rats are similar to MSCs from young rats. However when induced to turn into bone, fat and migrate towards SDF1, young MSCs are significantly more responsive than MSCs from OVX and adult control rats. The poor homing ability and differentiation of the stem cells and their retention may result in a reduction in bone formation leading to delayed union in fractures of osteoporotic patients(4)

Introduction. Subchondral insufficiency fracture of the femoral head (SIF) is a recently proposed concept. It is generally seen in elderly people, however, some young adults have also been reported to suffer from this fracture. The purpose of this study was to investigate the clinical results of a transtrochanteric anterior rotational osteotomy (ARO) performed in young adults with SIF. Methods. This study focused on young SIF cases (age range from 10 to 29 years). Five patients were diagnosed to have SIF at our institution and conservative treatment was initially performed. The symptoms resolved in 1 case while the other 4 cases showed progression of a collapse. In these 4 cases, ARO was performed, since the fractured area was located in the anterosuperior portion of the femoral head. The average age of the patients was 22 years (range, 16 to 29 years) at the time of surgery, consisting of 2 men and 2 women. Results. All cases were followed-up and the average follow-up period was 3.4 years (range, 1.8 to 6.8 years). The average preoperative Harris hip score was 67 points, which improved to an average of 93 points at the latest follow-up. Radiographically, the fractured lesion healed and no progression of a collapse was observed in any of the 4 cases. Conclusion. In the majority of SIF cases, only the anterosuperior portion of the femoral head is involved by the fracture. When considering the optimal surgical treatments for SIF, ARO may be one of the useful options, especially for the treatment of young patients

We have undertaken a series of clinical trials over the last 20 years to look at different bearing surface combinations in young adults. We continue to follow these patients well beyond the planned duration of the trials and new information is constantly becoming available. The first trial compared ceramic-on-ceramic with ceramic-on-standard-polyethylene. These patients have now been followed for 20 years with significant wear in the polyethylene group but virtually identical revision rates. The second trial ceramic-on-ceramic, cobalt-chrome-on-standard-polyethylene and cobalt-chrome-on-cross-linked-polyethylene. In this group the ceramic-on-ceramic patients have the lowest revision rate; the ceramic-on-polyethylene group demonstrates a lower wear rate than cobalt-chrome-on-polyethylene. The third trial looks at cobalt-chrome versus zirconium on either cross-linked polyethylene or conventional polyethylene. At 10 years there remains no evidence of improved performance from the zirconium surface as compared to cobalt-chrome. The cross-linked polyethylene group is clearly outperforming the conventional polyethylene in terms of wear rate but at 10 years the revision rates remain the same in all groups. Cross liked polyethylene appears to be the major determining factor in prosthetic longevity and appears to be more important than the counter face material

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells. Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation

Knee ligament injury is one of the most frequent sport injuries and ligament reconstruction has been used to restore the structural stability of the joint. Cycling exercises have been shown to be safe for anterior cruciate ligament (ACL) reconstruction and are thus often prescribed in the rehabilitation of patients after ligament reconstruction. However, whether it is safe for posterior cruciate ligament (PCL) reconstruction remains unclear. Considering the structural roles of the PCL, backward cycling may be more suitable for rehabilitation in PCL reconstruction. However, no study has documented the differences in the effects on the knee kinematics between forward and backward pedaling. Therefore, the current study aimed to measure and compare the arthrokinematics of the tibiofemoral joint between forward and backward pedaling using a biplane fluoroscope-to- computed tomography (CT) registration method. Eight healthy young adults participated in the current study with informed written consent. Each subject performed forward and backward pedaling with an average resistance of 20 Nm, while the motion of the left knee was monitored simultaneously by a biplane fluoroscope (ALLURA XPER FD, Philips) at 30 fps and a 14-camera stereophotogrammetry system (Vicon, OMG, UK) at 120 Hz. Before the motion experiment, the knee was CT and magnetic resonance scanned, which enabled the reconstruction of the bones and articular cartilage. The bone models were registered to the fluoroscopic images using a volumetric model-based fluoroscopy-to-CT registration method, giving the 3-D poses of the bones. The bone poses were then used to calculate the rigid-body kinematics of the joint and the arthrokinematics of the articular cartilage. In this study, the top dead center of the crank was defined as 0° so forward pedaling sequence would begin from 0° to 360°. Compared with forward pedaling, for crank angles from 0° to 180°, backward pedaling showed significantly more tibial external rotation. Moreover, both the joint center and contact positions in the lateral compartment were more anterior while the contact positions in the medial compartment was more posterior, during backward pedaling. For crank angles from 180° to 360°, the above-observed phenomena were generally reversed, except for the anterior-posterior component of the contact positions in the medial compartment. Forward and backward pedaling displayed significant differences in the internal/external rotations while the rotations in the sagittal and frontal planes were similar. Compared with forward cycling, the greater tibial external rotation for crank angles from 0° to 180° during backward pedaling appeared to be the main reason for the more anterior contact positions in the lateral compartment and more posterior contact positions in the medial compartment. Even though knee angular motions during forward and backward pedaling were largely similar in the sagittal and frontal planes, significant differences existed in the other components with different contact patterns. The current results suggest that different pedaling direction may be used in rehabilitation programs for better treatment outcome in future clinical applications

Non-invasive, in vivo measurement of the three-dimensional (3-D) motion of the tibiofemoral joint is essential for the study of the biomechanics and functional assessment of the knee. Real-time magnetic resonance imaging (MRI) techniques enable the measurement of dynamic motions of the knee with satisfactory image quality and free of radiation exposures but are limited to planar motions in selected slice(s). The aims of the current study were to propose a slice-to-volume registration (SVR) method in conjunction with dual-slice, real-time MRI for measuring 3-D tibiofemoral motion; and to evaluate its repeatability during passive knee flexion. Eight healthy young adults participated in the current study, giving informed written consent as approved by the Institutional Research Board. A 3-T MRI system (Verio, Siemens, Erlangen, Germany) incorporated with a neck matrix coil was used to collect the MRI data. A 3-D scanning using the VIBE sequence was used to collect the volumetric data of the knee at fully extended position (TR = 4.64 ms, TE = 2.3 ms, flip angle = 15°, in-plane resolution = 0.39 × 0.39 mm. 2. and slice thickness = 0.8 mm). A real-time MRI using the refocused radial FLASH sequence (TR = 4.3 ms, TE = 2.3 ms, flip angle = 20°, in-plane resolution = 1.0 × 1.0 mm. 2. , slice thickness = 6 mm) was used to acquire a pair of image slices of the knee at a frame rate of 3 fps during passive flexion. The volumetric MRI data sets were segmented for the femur and tibia/fibula to isolate the sub-volumes containing bone segments. A slice-to-volume registration method was then performed to determine the 3-D poses of the bones based on the spatial matching between sub-volume of the bones and the real-time image slices. The bone poses for all frames were used to calculate the rigid-body kinematics of the tibiofemoral joint in terms of the flexion/extension (FE), internal/external rotation (IR/ER), abduction/adduction (Abd/Add) and joint center translations along three anatomical axis of the tibia. The procedures were carried out five times for repeatability analysis. The standard deviation (SD) of the rigid-body kinematics for each frame from the five trials were calculated and then averaged across all frames to give quantitative measures of the repeatability of the kinematic variables. The repeatability analysis showed that the mean±SD of the averaged SD in FE, Abd/Add and IR/ER components across all subjects were 0.25±0.09, 0.46±0.13 and 0.77±0.16 degrees, respectively. The corresponding values for the joint translations in anterior/posterior, proximal/distal and medial/lateral directions were 0.21±0.04, 0.11±0.03 and 0.43±0.09 mm. An SVR method in conjunction with dual-slice real-time MRI has been successfully developed and its repeatability in measuring 3-D motion of the tibiofemoral joint evaluated. The results show that the proposed method is capable of providing rigid-body kinematics with sub-millimeter and sub-degree precision (repeatability). The proposed SVR method using real-time MRI will be a valuable tool for non-invasive, functional assessment of the knee without involving ionizing radiation, and may be further developed for joint stability assessment

Objectives. Whilst gait speed is variable between healthy and injured adults, the extent to which speed alone alters the 3D in vivo knee kinematics has not been fully described. The purpose of this prospective study was to understand better the spatiotemporal and 3D knee kinematic changes induced by slow compared with normal self-selected walking speeds within young healthy adults. Methods. A total of 26 men and 25 women (18 to 35 years old) participated in this study. Participants walked on a treadmill with the KneeKG system at a slow imposed speed (2 km/hr) for three trials, then at a self-selected comfortable walking speed for another three trials. Paired t-tests, Wilcoxon signed-rank tests, Mann-Whitney U tests and Spearman’s rank correlation coefficients were conducted using Stata/IC 14 to compare kinematics of slow versus self-selected walking speed. Results. Both cadence and step length were reduced during slow gait compared with normal gait. Slow walking reduced flexion during standing (10.6° compared with 13.7°; p < 0.0001), and flexion range of movement (ROM) (53.1° compared with 57.3°; p < 0.0001). Slow walking also induced less adduction ROM (8.3° compared with 10.0°; p < 0.0001), rotation ROM (11.4. °. compared with 13.6. °. ; p < 0.0001), and anteroposterior translation ROM (8.5 mm compared with 10.1 mm; p < 0.0001). Conclusion. The reduced spatiotemporal measures, reduced flexion during stance, and knee ROM in all planes induced by slow walking demonstrate a stiff knee gait, similar to that previously demonstrated in osteoarthritis. Further research is required to determine if these characteristics induced in healthy knees by slow walking provide a valid model of osteoarthritic gait. Cite this article: N. Mannering, T. Young, T. Spelman, P. F. Choong. Three-dimensional knee kinematic analysis during treadmill gait: Slow imposed speed versus normal self-selected speed. Bone Joint Res 2017;6:514–521. DOI: 10.1302/2046-3758.68.BJR-2016-0296.R1

AIM. Avascular necrosis (AVN) of the femoral head is a potentially debilitating disease of the hip in young adults. Impaction bone grafting (IBG) of morcellised fresh frozen allograft is used in a number of orthopaedic conditions. This study has examined the potential of skeletal stem cells (SSC) to augment the mechanical properties of impacted bone graft and we translate these findings into clinical practice. STUDY DESIGN. We have examined the effect of SSC density on augmentation of bone formation. An in vitro model was developed to replicate the surgical IBG process. Plain allograft was used as the control, and the SSC's seeded at a density of 5×103, 5×104 and 2×105 cells per cc of allograft for the experimental groups. All samples were cultured for 2 weeks and mechanically tested to determine shear strength using the Mohr Coulomb failure curve. The approach was translated to 3 patients with early avascular necrosis (AVN) of the femoral head. The patient's bone marrow was concentrated in theatre using a centrifugation device and the concentrated fraction of SSC's were seeded onto milled allograft. The patient's necrotic bone was drilled, curetted and replaced with impacted allograft seeded with SSC's. Osteogenic potential of concentrated and unconcentrated marrow was simultaneously compared in vitro by colony forming unit assays. RESULTS. The mechanical properties of the impacted allograft was significantly improved as a function of increasing SSC density. The difference compared to the control plain allograft was highly significant at the 2×105 level (p=0.001). Autologous SCC's on impacted bone allograft was subsequently applied in 3 patient cases and up to two year follow up demonstrates no deleterious effect. Critically the analysis of concentrated marrow demonstrated a higher SSC count in vitro than plain marrow aspirate. DISCUSSION. We have demonstrated the potential of skeletal stem cells to augment the mechanical properties of impacted bone allograft in a laboratory model and subsequently translated these findings into a new technique for the treatment of AVN of the femoral head. Such an approach provides not only improved mechanical support to the overlying cartilage but critically improved biology for new bone formation. The early clinical results are encouraging and indicate potential use also in fracture non-unions and void filling of bone defects

Introduction. Although osteonecrosis of the femoral head has been observed in young adult patients with autoimmune diseases such as SLE and MCTD that are treated by corticosteroids, the pathogenesis of the osteonecrosis remains unclear. We established a rat model with osteonecrosis of the femoral head by injecting lipopolysaccharide (LPS) and corticosteroid, and assessed consequences of the histopathological alteration of the femoral head, the systemic immune response, and the lipid synthesis. Methods. Male Wistar rats were given 2 mg/kg LPS intravenously on days 0 and 1 and intramuscularly 20 mg/kg methylprednisolone on days 2, 3, and 4. The animals were sacrificed 1, 2, 3, or 4 weeks after the last injection of the methylprednisolone. Histopathological and biochemical analyses were performed every week. The bone samples were then processed for routine hematoxylin and eosin staining to assess the general architecture and injury of the tissue. The triglyceride and the total cholesterol concentrations in the PRP were measured. The levels of various cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ, TNF-α) in blood samples were measured. Results. The body weight of the rats over time decreased for 2 weeks but had recovered by week 4. The plasma triglyceride concentrations had decreased significantly by weeks 2 and 3. The total plasma cholesterol concentrations had increased significantly by week 1 but then decreased significantly by week 4. The plasma concentrations of IL-1?α, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ and TNF-α had increased significantly by week 1. These cytokines can all be induced by toll-like receptor 4 (TLR4) signaling. We defined osteonecrosis as the diffuse presence of empty lacunae or pyknotic nuclei of osteocytes in the bone trabeculae, accompanied by surrounding bone marrow cell necrosis. Osteonecrosis of the femoral head was observed only in the epiphysis of the femoral head in sacrificed specimen every week. Histological analysis revealed osteocytic death surrounded by necrotic bone marrow with or without repaired tissue. Conclusion. We established a new rat model of corticosteroid-induced femoral head osteonecrosis. The necrosis that is generated in this model is similar to that seen in patients treated with corticosteroid. In particular, the necrotic lesion was exclusively observed in the proximal epiphysis. LPS is known to activate the immune system via the TLR4 signaling pathway. It has been recognized that the unique immunogenic effects of LPS promote autoimmune disease . LPS and methylprednisolone induced osteonecrosis of the femoral head in rats and this was associated with a disruption of the innate immune system and lipid synthesis. These findings suggest that the TLR4 signaling pathway plays an important role in the pathogenesis for osteonecrosis of the femoral head