Project description:Gli1+ progenitors are considered as metaphyseal mesenchymal progenitors in the distal femur and proximal tibia under the growth plate. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of Gli1+ progenitors in response to methylprednisolone.
Project description:We used single cell RNA sequencing (scRNA-seq) to identify femur and tibia osteoblast cell stress response pathway to misfolding of type I procollagen with Gly610->Cys substitution in the triple helical region of alpha2(I) chain.
Project description:BackgroundDistal femur and proximal tibia replacements as limb-salvage procedures with good outcome parameters for patients with tumours have been broadly described. However, the overall midterm outcome in a mixed, heterogeneous patient collective is still unclear.Patients and methodsWe retrospectively analysed 59 consecutive patients (33 for primary and 26 for revision surgery) between 1998 and 2017. Indication for implantation was tumour (n=16), periprosthetic fracture (n=14), traumatic fracture (n=14), infection (n=10), aseptic loosening (n=3), and pathological fracture (n=2). The mean follow-up duration was 3 years. Clinical functions were evaluated by Toronto Extremity Salvage Score and Knee Society Score. Knee extension and flexion force were measured.ResultsThe overall survival rate of arthroplasties was 59% (n=35). Major complications were observed in 36 (61%) patients. During the follow-up period, 14 (24%) patients died. We recorded periprosthetic joint infection in 21 (36%) patients, recurrence of tumour in two (3%), and aseptic implant failure in three (5%). The mean Toronto Extremity Salvage Score was 66±33, and the mean Knee Society Score was 49±30. The mean extension force on the operated side was significantly reduced at 60° and 180° compared to the healthy side (p=0.0151 and p=0.0411, respectively).ConclusionDistal femur and proximal tibia replacements showed limited clinical function in a heterogeneous patient collective. Indication for implantation should be considered carefully.
Project description:Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 μm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual-energy X-ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 μm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.
Project description:The concomitance of ipsilateral physeal fractures of the distal femur and the proximal tibia is an extremely scarce entity. It is conceptually similar to floating knee in the pediatric population.One case with this injury is reported in a 16-year-old teenager. He was treated surgically by close reduction and internal fixation. The diagnosis of the tibial fracture was initially missed, and the fracture was seen on the post-operative radiographs. Orthopedic treatment was made for this injury. 2 years after, no angular deformity neither shortening of the limb were found.These rare injuries could have serious immediate and remote complication with a considerable functional impact. The diagnosis of proximal tibia physeal fracture could be missed in the context of a concomitant more impressive distal femur fracture. The possibility of a combination of these two injuries should then be kept in mind. Anatomic reduction should be made as soon as possible using a gentle technique, and attention should be given to the diagnosis of the neurovascular complications.
Project description:Increased contact pressures of the osteoarthritic joint can lead to underlying osseous injury, with resultant marrow edema changes of the subchondral bone. These osteoarthritis-related bone marrow lesions can subsequently lead to persistent pain and further disability. Limited joint preservation treatment options exist to alleviate symptoms or potentially alter the natural history of the affected joint; however, recent success with injectable calcium phosphate has provided early pain relief and may provide a scaffold for endogenous repair mechanisms. In this Technical Note, a comprehensive surgical approach using injectable calcium phosphate to target bone marrow lesions of the proximal tibia and distal femur is presented. Critical technique considerations include the use of magnetic resonance and fluoroscopic imaging to target the area of the subchondral bone while refraining from overfilling and/or forced pressurization during delivery and the use of postinjection arthroscopy to prevent potential injurious sequelae.
Project description:Computed tomography and finite element modeling were used to assess bone structure at the knee as a function of time after spinal cord injury. Analyzed regions experienced degradation in stiffness, mineral density, and content. Changes were well described as an exponential decay over time, reaching a steady state 3.5 years after injury.IntroductionSpinal cord injury (SCI) is associated with bone fragility and an increased risk of fracture around the knee. The purpose of this study was to investigate bone stiffness and mineral content at the distal femur and proximal tibia, using finite element (FE) and computed tomography (CT) measures. A cross-sectional design was used to compare differences between non-ambulatory individuals with SCI as a function of time after injury (0-50 years).MethodsCT scans of the knee were obtained from 101 individuals who experienced an SCI 30 days to 50 years prior to participation. Subject-specific FE models were used to estimate stiffness under axial compression and torsional loading, and CT data was analyzed to assess volumetric bone mineral density (vBMD) and bone mineral content (BMC) for integral, cortical, and trabecular compartments of the epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia.ResultsBone degradation was well described as an exponential decay over time (R2 = 0.33-0.83), reaching steady-state levels within 3.6 years of SCI. Individuals at a steady state had 40 to 85% lower FE-derived bone stiffness and robust decreases in CT mineral measures, compared to individuals who were recently injured (t ≤ 47 days). Temporal and spatial patterns of bone loss were similar between the distal femur and proximal tibia.ConclusionsAfter SCI, individuals experienced rapid and profound reductions in bone stiffness and bone mineral at the knee. FE models predicted similar reductions to axial and torsional stiffness, suggesting that both failure modes may be clinically relevant. Importantly, CT-derived measures of bone mineral alone underpredicted the impacts of SCI, compared to FE-derived measures of stiffness.Trial registrationClinicalTrials.gov (NCT01225055, NCT02325414).
Project description:Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme beta-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation. In this study we performed microarray analysis of ascending aortas from normal and MPS VII mice, trying to find out possible genes responsible for the phenotype observed. In addition, during our breeding strategy, we noticed that some MPS VII mice had less dilated aortas, and we proposed that an yet-unidentified gene could be responsible for the difference observed. We therefore included in the analysis two MPS VII mice with aortas that were not dilated. Total RNA extracted from ascending aortas from 3 Normal mice, 3 MPS VII mice with dilated aortas and 2 MPS VII mice with aortas that were not dilated.