BMP-1 is the major procollagen-C-peptidase activating, besides fibrillar collagen types I-III, several enzymes and growth factors involved in the generation of extracellular matrix. This study investigated the effect of adding and inhibiting BMP-1 directly post fracture. Standardised femoral fractures were stabilized by an intramedullary nail in 12 week-old female C57Bl/6J mice. We injected either 20 µL recombinant active BMP-1, activity buffer or the BMP-1 specific inhibitor “sizzled”. After 7, 14 and 28 days, mice were sacrificed. Femurs were dissected and paraffin slides were prepared. Callus composition was divided into soft tissue, mineralized and cartilaginous callus. Murine MC3T3 pre-osteoblastic cells were kept in culture adding BMP-1 and sizzled during osteoblastic differentiation. Putative cytotoxicity was determined using MTT-vitality assay. Cell calcification, collagen deposition, and BMP-2 and myostatin protein quantity were characterized. Adding BMP-1 displayed a weak positive effect on the outcome. After 7 days, more mineralised callus was present, meanwhile the cartilaginous callus was apparently remodelled at higher rate. In the case of BMP-1 inhibition, we observed more cartilaginous callus, which may indicate reduced stability. In cell culture, we could observe a high interference with mineralisation capabilities depending on the stage of osteoblastic development when adding BMP-1 or inhibiting it. Addition and inhibition impaired myostatin (anti-osteogen) and BMP-2 (pro-osteogen) expression. Interfering with BMP-1 homeostasis in this early stage of fracture repair seems to have rather negative effects. Inhibition apparently yields lower callus quality while the addition of BMP-1 does not significantly accelerate the healing outcome. Cell culture experiments show that BMP-1 application after 7 days of healing leads to higher collagen output but has no effect on mineralisation. This may suggest that BMP-1 application at a later time-point may lead to more pronounced beneficial effects on fracture repair.
Purpose of study:. In polytrauma patients (ISS > 16) early long bone and pelvic fracture fixation (< 24 hours post injury) has been shown to be beneficial. Surgery in the presence of subclinical hypo perfusion (SCH) (normal vital signs with a serum lactate > 2.5 mmol/L) may be detrimental. This study aimed to investigate the effect of fracture fixation in polytrauma patients with SCH. Description of methods:. We performed a retrospective database review of polytrauma patients (ISS > 16) with significant long bone or pelvic fractures (extremity NISS> 9) who underwent surgical fracture stabilisation within 48 hours of injury. In the group of patients with normal vital signs (mean arterial pressure (MAP) > 60 mmHg and heart rate (HR) < 110 beats/min) we compared outcomes of those with normal lactate (< 2.5 mmol/L) prior to surgery with patients that had a raised lactate (> 2.5 mmol/L). Results:. Of the 36 patients with normal preoperative vital signs, 17 had normal serum lactates (control group) and 19 abnormal (SCH group). The SCH group required more inotropes in the first 24 hours post-surgery (p=0.02), had higher Sequential Organ Failure Assessment (SOFA) scores on day three (p=0.003) and showed a trend towards higher SOFA scores on day seven (p=0.061). Conclusion:.
Treatment of segmental bone defects remains a major clinical problem, and innovative strategies are often necessary to successfully reconstruct large volumes of bone. When fractures occur, the resulting hematoma serves as a reservoir for growth factors and a space for cell infiltration, both crucial to the initiation of bone healing. Our previous studies have demonstrated very clear ultrastructural differences between fracture hematomas formed in normally healing fractures and those formed in segmental bone defects. However, there is little information available regarding potential differences in the underlying gene expression between hematomas formed in normal fractures, which usually heal by themselves, and segmental bone defects, which do not. Therefore, the aim of this study was to identify differences in gene expression within hematomas collected from 0.5 mm (normal fracture) and 5 mm (segmental bone defect) fracture sites during the earliest stages of bone healing. Osteotomies of 0.5 and 5 mm in the femur of Fisher 344 rats were stabilized with external fixators (RISystem AG). After 3 days the rats were sacrificed, and the fracture hematomas were collected for RNA-sequencing. Ingenuity pathway analysis (IPA) was used to identify upstream regulators and biological functions that were significantly enriched with differentially expressed genes from the RNA-sequencing analysis. Animal procedures were conducted following the IACUC protocol of the UT Health Science Center San Antonio. Key upstream regulators of bone formation were less active (e.g. TGFB1, FGF2, SMAD3) or even inhibited (e.g. WNT3A, RUNX2, BMP2) in non-healing defects when compared to normally healing fractures. Many upstream regulators that were uniquely enriched in healing defects were molecules recently discovered to have osteogenic effects during fracture healing (e.g. GLI1, EZH2). Upstream regulators uniquely enriched in non-healing defects were mainly involved in an abnormal modulation of hematopoiesis, revealing evidence of impaired maturation of functional macrophages and cytokines (e.g. IL3, CEBPE), both essential for successful bone healing. In addition, the enrichment pattern suggested a dysregulation of megakaryopoiesis (e.g. MRTFA, MRTFB, GATA2), which directly affects platelet production, and therefore fracture hematoma formation. Remarkably, the organization of the ECM was the most significantly enriched biological function in the normally healing fractures, and implies that the defect size directly affected the structural properties within the fracture hematoma. Conversely, genes encoding important ECM components (e.g. BGN, various collagens, IBSP, TNC), cell adhesion molecules, MMPs (MMP2), and TIMPs were all significantly downregulated in non-healing defects. Our most recent findings reveal new important key molecules that regulate defect size-dependent fracture healing. Combined with our previous results, which identified structural differences in fracture hematomas from both types of defects, current findings indicate that differential expression of genes is dictated by the structural properties of the hematomas formed during early fracture healing. Consequently, creating a bioscaffold that mimics the structure of normal fracture hematomas could be the first step towards developing new orthoregenerative treatment strategies that potentiate healing of large bone defects and non-healing fractures.
Methods: 24 sheep (Merino wethers, mean age 5.6years, mean weight 39.1kg) underwent the trauma model 2 with a severe soft tissue damage and a multifragmentary, distal femur fracture as well as initial stabilisation with an external fixator. After five days of soft tissue recovery, the animals were definitively operated with an internal fixator (LCP) randomised either by a minimally invasive or open approach. The sheep were sacrificed after 4 and 8 weeks (two groups), mechanical testing performed and statistically analysed with ANOVA test. Results: After 4 weeks, torsional rigidity is significantly higher in the MIPO group (30.1r10.6(SD)%) of fractured to intact bones, p<
0.05) compared to ORIF group (9.8r12.4(SD)%), while ultimate torque also shows increased values for MIPO technique (p=0.11). After 8 weeks, the differences in mechanical properties levelled out, but still higher values for the MIPO group (p=0.36/p=0.26). Conclusion: In the early stage of fracture healing, minimally invasive plate osteosynthesis shows advanced healing pattern compared to open fixation technique. This advantage seems to level out over time.
The immunosuppressive drug rapamycin (RAPA) prevents rejection in organ transplantation by inhibiting interleukin-2-stimulated T-cell division. RAPA has also been suggested to possess strong anti-angiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF). Because VEGF is a key growth factor in fracture healing, the present study was conducted to analyze the effect of RAPA on bone repair. For the herein introduced study 35 SKH-1Hr mice were treated by a daily intraperitoneal (i.p.) injection of RAPA (1.5mg/kg/d) from the day of fracture until sacrifice. Two or five weeks after fracture, animals were killed and bone healing was analyzed using radiological (n=16 at 2 weeks; n=16 at 5 weeks), biomechanical (n=2x8), and histomorphometric (n=2x8)
X-ray analyses demonstrated that RAPA treatment inhibits callus formation after 2 weeks of fracture healing. The radiologically observed lack of callus formation after RAPA treatment was confirmed by histomorphometric analyses, which revealed a significantly diminished callus size and a reduced amount of bone formation when compared to vehicle-treated controls. Biomechanical testing further demonstrated that RAPA significantly reduces torsional stiffness of the callus (11.5±5.9% of the contralateral unfractured femur vs. 28.3±13.9% in controls; p<
0.05). Of interest, this was associated with a decrease of callus VEGF and PCNA expression. After 5 weeks of fracture healing, however, the negative impact of RAPA on fracture healing was found blunted and the radiological, histomorphometric and biomechanical differences observed after 2 weeks could not longer be detected. We demonstrate that RAPA treatment leads to a severe alteration of early fracture healing. The negative action of RAPA on fracture repair at 2 weeks is most probably due to an inhibition of VEGF expression within the callus as suggested by the results of the Western blot analysis, demonstrating during the early phase of fracture healing a significantly reduced expression of VEGF and PCNA after RAPA treatment. This indicates a substantial alteration of cell proliferation and angiogenic vascularization during initial fracture healing. Since T-cells contribute to delayed fracture healing, RAPA may promote bone healing at later stages due to a reduction of interleukin-2-stimulated Tcell division.
Metal-on-metal hip resurfacing prostheses are a relatively recent intervention for relieving the symptoms of common musculoskeletal diseases such as osteoarthritis. While some short term clinical studies have offered positive results, in a minority of cases there is a recognised issue of femoral fracture, which commonly occurs in the first few months following the operation. This problem has been explained by a surgeon's learning curve and notching of the femur but, to date, studies of explanted
Metal-on-metal hip resurfacing prostheses are a relatively recent intervention for relieving the symptoms of common musculoskeletal diseases such as osteoarthritis. While some short term clinical studies have offered positive results, in a minority of cases there is a recognised issue of femoral fracture, which commonly occurs in the first few months following the operation. This problem has been explained by a surgeon's learning curve and notching of the femur but, to date, studies of explanted
Purpose: The aim of this study was to compare the results and length of stay of patients of
The aim of this study was to compare the results and length of stay of patients of early (within 12 hours) versus conventional (after 48 hours) ankle fixation our hospital. It was a retrospective study over 18 month period (July 2004 - Dec 2005) including 200 Patients (aged 16 or more). We looked into age, place of living, Weber classification, mechanism of injury, comorbidities especially diabetes, addictions mainly smoking, etc. Overlying skin condition, the amount of swelling at presentation, associated ankle dislocation or talar shift, acute medical comorbidities, injury types-open or closed were classified accordingly.Introduction
Methods of study
The stem design in total hip arthroplasty (THA) is constantly evolving. The impact of the collar on the risk of periprosthetic fracture remains controversial. This study aimed to determine whether adding a collar to the femoral stem impacts the
We present a consecutive case cohort of the first 100 Birmingham Hip Resurfacing (BHR)'s in 90 patients with a minimum follow up of 20 years. All procedures were performed by a single surgeon having commenced the study in 1998. The original cohort included 68 males with 75 hips (7 bilateral) and 22 females with 25 hips (3 bilateral). The mean age at index procedure was 52. Patients were recalled to review in clinic as per Medicines and Healthcare products Regulatory Agency guidelines with x-rays, metal ions and Harris Hip Scores recorded. After a minimum of 20 year follow-up review the known overall revision rate is 11%. 11 have died and 7 have been lost to review. In males the known revision rate is 4/75 (5%), 3 of which were due to
Hip fracture principally affects the frailest in society, many of whom are care dependent, and are disproportionately at risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England. We conducted a cohort study of patients with hip fracture recorded in the National Hip Fracture Database between 1st February 2019 and 31st October 2020, in England. Data were linked to Hospital Episode Statistics to quantify patient characteristics and comorbidities, Office for National Statistics mortality data, and Public Health England's SARS-CoV-2 testing results. Multivariable Cox regression examined determinants of 90-day mortality. Excess mortality attributable to COVID-19 was quantified using Quasi-Poisson models. Analysis of 102,900 hip fractures (42,630 occurring during the pandemic) revealed that amongst those with COVID-19 infection at presentation (n=1,120) there was a doubling of 90-day mortality; hazard ratio (HR) 2.05 (95%CI 1.86–2.26), while for infections arising between 8–30 days after presentation (n=1,644) the figure was even higher at 2.52 (2.32–2.73). Malnutrition [1.44 (1.19–1.75)] and non-operative treatment [2.89 (2.16–3.86)] were the only modifiable risk factors for death in COVID-19 positive patients. Patients with previous COVID-19 initially had better survival compared to those who contracted COVID-19 around the time of their hip fracture; however, survival rapidly declined and by 365 days the combination of hip fracture and COVID-19 infection was associated with a 50% mortality rate. Between 1st January and 30th June 2020, 1,273 (99.7%CI 1,077–1,465) excess deaths occurred within 90 days of hip fracture, representing an excess mortality of 23% (20%–26%), with most deaths occurring within 30 days. COVID-19 infection more than doubled
The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase.Aims
Methods
Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq).Aims
Methods
Despite higher rates of revision after total hip arthroplasty (THA) being reported for uncemented stems in patients aged > 75 years, they are frequently used in this age group. Increased mortality after cemented fixation is often used as a justification, but recent data do not confirm this association. The aim of this study was to investigate the influence of the design of the stem and the type of fixation on the rate of revision and immediate postoperative mortality, focusing on the age and sex of the patients. A total of 333,144 patients with primary osteoarthritis (OA) of the hip who underwent elective THA between November 2012 and September 2022, using uncemented acetabular components without reconstruction shells, from the German arthroplasty registry were included in the study. The revision rates three years postoperatively for four types of stem (uncemented, uncemented with collar, uncemented short, and cemented) were compared within four age groups: < 60 years (Young), between 61 and 70 years (Mid-I), between 71 and 80 years (Mid-II), and aged > 80 years (Old). A noninferiority analysis was performed on the most frequently used designs of stem.Aims
Methods
Aims. There are concerns regarding initial stability and
The August 2013 Trauma Roundup. 360 . looks at: reverse oblique fractures do better with a cephalomedullary device; locking screws confer no advantage in tibial plateau fractures; it’s all about the radius of curvature; radius of curvature revisited; radial head replacement in complex elbow reconstruction; stem cells in
Introduction: The results of metal-on-metal hip resurfacing (MOMHR) from inventing centres show excellent function with low revision rates in the short to intermediate term. This study investigated whether similar results could be achieved in an independent unit. Methods: All cases of MOMHR were identified since its introduction in our centre in 1999, and cases with less than 18 months follow-up excluded. Outcome was assessed by Oxford Hip Score (OHS), and UCLA activity score. Complications and further surgery was recorded. Pre-, post-op and follow-up radiographs were reviewed. Results: 358 resurfacings in 315 patients (238 Birmingham hip resurfacings and 120 Cormet 2000, 8 surgeons). 13 (3.6%) revisions: 4
“Get It Right First Time” (GIRFT) and NHS England’s Best Practice Tariff (BPT) have published directives advising that patients over the ages of 65 (GIRFT) and 69 years (BPT) receiving total hip arthroplasty (THA) should receive cemented implants and have brought in financial penalties if this policy is not observed. Despite this, worldwide, uncemented component use has increased, a situation described as a ‘paradox’. GIRFT and BPT do, however, acknowledge more data are required to support this edict with current policies based on the National Joint Registry survivorship and implant costs. This study compares THA outcomes for over 1,000 uncemented Corail/Pinnacle constructs used in all age groups/patient frailty, under one surgeon, with identical pre- and postoperative pathways over a nine-year period with mean follow-up of five years and two months (range: nine months to nine years and nine months). Implant information, survivorship, and regular postoperative Oxford Hip Scores (OHS) were collected and two comparisons undertaken: a comparison of those aged over 65 years with those 65 and under and a second comparison of those aged 70 years and over with those aged under 70.Aims
Methods
As a treatment for end-stage elbow joint arthritis, total elbow replacement (TER) results in joint motions similar to the intact joint; however, bearing wear, excessive deformations and/or