We compared the length of hospitalisation, rate of infection, dislocation of the hip and revision, and mortality following primary hip and knee arthroplasty for osteoarthritis in patients with Alzheimer’s disease (n = 1064) and a matched control group (n = 3192). The data were collected from nationwide Finnish health registers. Patients with Alzheimer’s disease had a longer peri-operative hospitalisation (median 13 days vs eight days, p < 0.001) and an increased risk for hip revision with a hazard ratio (HR) of 1.76 (95% confidence interval (CI) 1.03 to 3.00). Dislocation was the leading indication for revision. There was no difference in the rates of infection, dislocation of the hip, knee revision and short-term mortality. In long-term follow-up, patients with Alzheimer’s disease had a higher mortality (HR 1.43; 95% CI 1.22 to 1.70), and only one third survived ten years post-operatively. Increased age and comorbidity were associated with longer peri-operative hospitalisation in patients with Alzheimer’s disease. Cite this article: Bone Joint J 2015;97-B:654–61

Both total joint arthroplasty (TJA) and Alzheimer's Disease (AD) are prevalent in elderly populations. It is the goal of this study to determine if the presence of implant metals originating from TJA correlates with the onset with higher implant metal content in the brain and AD pathology. Tissue samples from four brain regions of 701 (229 with TJA) participants from an ongoing longitudinal cohort study (Rush Memory and Aging Project) was analyzed including the inferior-temporal-cortex (ITC), which is associated with early onset of AD. Implant metal (Co, Cr, Mo, Ti, Al) content was determined by ICP-MS. Comparisons were conducted between the no-TJA-group and a TJA group. Due to the higher likelihood of Co release the TJA group was further differentiated in a THA (N=146) and a TKA/TSA (N=83) group. Diffuse and neuritic amyloid plaques and phosphorylated tau were assessed and summarized as standard measures of AD pathology. We used separate linear regression models adjusted for age, sex, education, and APOɛ4-status for the associations of all metals (log-transformed) with global AD pathology, amyloid plaques, and phosphorylated tau. The THA group had higher cobalt content across all brain regions (p=0.003) and within the ITC (p=0.051) compared to the no-TJA group, whereas the TKA/TSA group did not. Across all tissue samples, Co was associated with higher amyloid load (β=0.35, p=0.027), phosphorylated tau (β=0.47, p=0.011), and global AD pathology (β=0.19, 0.0004) in the ITC. The presence of TJA itself was not associated with AD pathology. We showed that only Co content was higher within the ITC in persons with THA. We found among all tested metals that Co was consistently associated with AD pathology. Although we found an association of cobalt with AD pathology, the cross-sectional nature of this study does not allow the determination of cause and effect

Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms. Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment. CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies). CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD

Introduction. Patients with pre-existing dementia are more susceptible to hip fracture due to various risk factors such as age, decreased activity leading to sarcopenia and osteoporosis, Vitamin D deficiency and presence of Apolipoprotein gene. The mortality associated with dementia and fracture neck of femurs was thought to be 2.3 times more than that of patients with intact cognitive function. The aim of this study is to assess the mortality of patients at 28 days, 4 months and one year after undergoing surgery for fracture neck of femurs. Methods. A retrospective study of 184 patients admitted with fracture neck of femur and had dementia for a period from April 2014 to August 2016 were carried out. The patient demographics, AMT score, pre-operative co-morbidities, perioperative mortality and one year mortality were analysed. Results. A total no. of 1007 patients was admitted with fracture neck of femurs during the study period. 184 patients were found to have pre fracture dementia. The mean age was87.088 years (Range 64–101). There was 42 males and 142 females. The average ASA grade was 2–3. 99 patients (53.8%) had Alzheimer's disease, 50 patients (27%) had vascular dementia and 35 patients (19.2%) had other types of dementia.94 patients (51%) had more than one co-morbidity. The average AMT score was 0.66(normal range 0–10). The total number of patients died was 114(62%). The overall mortality at 28 days was 24 %(44 patients=0.0001), 4 months was 46 %(84 patients) and one year was 62 %(114 patients, p=0.0001). In 90(49%) patients who had only dementia and no other co-morbidities(ASA grade 1–2) the mortality at 28 days was 20% (p=0.0051), 4 months was 40% and at one year 61%(p=0.0001). Conclusion. In our study we found that the overall mortality in patients with dementia and fracture neck of femurs is 62% and the perioperative mortality rate was 24%. The peri-operative mortality rate was 20% in patients with pure dementia. The mortally rate in dementia with fracture neck of femurs patients was far more than what is noted in the literature

Introduction: Oxidative stress occurs when reactive oxygen species (ROS) are produced faster than they can be removed by cellular defence mechanisms contributing to ageing, many chronic diseases, such as atherosclerosis, RA, Parkinson and Alzheimer’s disease and skeletal pathologies. Here we address the impact of ROS on the viability of early osteogenic precursors in the bone marrow and study the influence of estrogen on this interaction. Cells have a number of mechanisms to protect themselves from ROS, which are constantly being formed in the cell through normal metabolic pathways, such as Vitamin E, C and estrogen. Estrogen has been shown to prevent intracellular accumulation of peroxide and to attenuate oxidant-induced death of neuronal and endothelial cells. In addition, it contributes significantly to bone turnover and relieves postmenopausal symptoms. This study has focused on the potential anti-oxidant properties of estrogen against oxidative on bone marrow stromal cells. stress induced by H. 2. O. 2. Methods: Primary bone marrow stromal cells were pre-treated with several different doses between 10. −6. M – 10. −8. M of estrogen prior to H. 2. O. 2. administration at 0.08–0.4 mM 30% (v/v) for 2–24h. The cellular production of ROS was determined by using the free radical indicator DCFH-DA. Apoptosis was determined by morphological criteria. Results: H. 2. O. 2. induced an increase in apoptosis of osteoprogenitor cells (p< 0.05). Determination of apoptosis and cell number by nuclear staining, indicated that pre-treatment of bone marrow stromal cells with 17-beta estradiol reduced the apoptotic response induced by H. 2. O. 2. (p< 0.05) and restored cell number to control levels. In order to test the anti-oxidant activity of estrogen, the dye DCFH-DA was introduced in a cell free system in the presence or absence of 17-beta estradiol and H. 2. O. 2. The same experiment was repeated in the presence of bone marrow stromal cells. H. 2. O. 2. increased both intracellularly and extracellularly oxidant activity and estradiol has the capacity of modifying this activity both inside and outside the cell. Discussion: These data demonstrate the ability of estrogen, used at physiological doses, to block oxidant-induced apoptosis of osteoprogenitor cells. Estrogen appears to reduce the generation of ROS in these cells. These data could have important implications on the maintenance of osteogenic stem cells during fractures, ageing and disease

Introduction: This study aimed to analyse immunohis-tochemically the proteolysis of Amyloid Precursor Protein (APP) using Caspase-3-mediated APP proteolytic peptide (CMAP), beta-Amyloid (Aβ) and Active Caspase-3 in post-mortem human specimens in acute and chronic compressive myelopathy. Compressive myelopathy, occurring through traumatic fracture/dislocation of vertebrae, iatrogenic injury, cervical spondylotic myelopathy (CSM), or metastatic tumour, causes much socio-economic and emotional disability for patients as well as physical consequences. In such conditions, APP is recognised as an early and specifi c marker of axonal injury. The proteolysis of APP in both acute and chronic compressive myelopathy has not yet been described. Studies analysing axonal injury after brain trauma suggest a role for Caspase-3 in the cleavage of APP. 1. In addition, Caspase-3-mediated cleavage of APP has been found to be associated with the formation of Aβ, a neurotoxic protein thought to contribute to cell death in Alzheimer’s disease. 2. Furthermore, A? may subsequently encourage activation of Caspases −2, −3, and −6, the major effector molecules in apoptosis. 2. The current study addressed two hypotheses; that APP provides a substrate for the Caspase-3 enzyme, and, that this event is associated with Aβ production in the compressed spinal cord. Methods: Spinal cord material from 17 patients with documented SCI was analysed. The spatial distribution of cellular immunoreactivity was qualitatively assessed in injury due to trauma (n=5), iatrogenic event (n=1), CSM (n=6) and metastatic tumour (n=5). Morphological, immunohistochemical and immunofl uorescent techniques were used to investigate APP proteolysis. Results: Caspase-3, APP, CMAP and Aβ were present in anterior horn cells of the grey matter and axons of the white matter. An association was found between neuronal immunoreactivity and that of axons in motor tracts. Dual-immunolabelling revealed axonal co-localisation of CMAP with Aβ and Caspase-3 with Aβ. Although CMAP was present in axons which were immunoposi-tive for APP, an inverse relationship was found as each marker was limited to its own, distinct region, consistent with the theory that CMAP actively cleaves APP. In neurons, co-localisation occurred between Caspase-3 and Aβ, and CMAP with Aβ. No neuronal co-localisation was shown between CMAP and APP in the acute and chronic state. Discussion: Caspase-3 appears likely to contribute to the proteolytic cleavage of APP in compressive myelop-athy. CMAP was associated with the production of Aβ as demonstrated using single and dual immunolabelling. Furthermore, evidence is given for the association of Caspase-3 itself with the neurotoxic peptide, Aβ. It is possible that activation of Caspase-3 via these secondary mechanisms may trigger the advancement of the apoptotic cascade with the subsequent demise of the cell

Introduction: Apoptosis, or secondary cell death, has been demonstrated in a number of neurological conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and brain ischaemia. It is well established from studies of acute spinal cord injury that apoptosis seems an important factor in secondary cell death and irreversible neurological deficit. It is only recently that studies have emerged analysing secondary cell death in chronic injury to the cord. In this study, the spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathies due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). The study aimed to demonstrate apoptosis in compressive spinal cord injury and to analyse the spatial and temporal distribution of apoptosis in acute and chronic myelopathy. Method: Archival material from 21 spinal cords of patients with documented myelopathy during life and definitive evidence on post mortem examination were available for study. The spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathy due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). Immunohistochemical analysis of each specimen was conducted using markers of apoptosis, as well as the biochemical apoptotic marker TUNEL. A total of 1800 histopathological slides were analysed. Specimens were also analysed using confocal microscopy to identify the immunopositive cell type. A combination of morphological, immunohistochemical and in situ end-labelling techniques were used to investigate the mechanism of cell death in this experiment. The analytical techniques employed were aimed at showing firstly the presence of apoptosis and secondly the size and position of the damaged regions. Results: Positivity for active Caspase-3, DNA-PKCS, PARP, TUNEL and active Caspase-9 was found in glia (oligodendrocytes and microglia) axons and neurons in both acute and chronic compression above, below and at the site of compression. In chronic compression, the severity of positivity for apoptotic immunological markers was positively correlated with the severity of white matter damage, as measured by APP immunostaining for axonal injury, and Wallerian degeneration. There was no correlation between the duration of chronic compression and immunopositivity for apoptotic markers. In acute SCI, axonal swellings were consistently positive for Caspases −9 and -3, suggesting mitochondrial activation of apoptotic pathways. Conclusion: Apoptosis occurs in both acute and chronic spinal cord injury. In acute compression, axonal injury is associated with apoptotic immunopositivity of glia and neurons. In chronic compression, apoptosis of oligodendrocytes and microglia correlates with demyelination of axons within the white matter

INTRODUCTION: Apoptosis, or secondary cell death, has been demonstrated in a number of neurological conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and brain ischaemia. It is well established from studies of acute spinal cord injury that apoptosis seems an important factor in secondary cell death and irreversible neurological deficit. It is only recently that studies have emerged analysing secondary cell death in chronic injury to the cord. In this study, the spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathies due to meta-static tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). The study aimed to demonstrate apoptosis in compressive spinal cord injury and to analyse the spatial and temporal distribution of apoptosis in acute and chronic myelopathy. METHOD: Archival material from 21 spinal cords of patients with documented myelopathy during life and definitive evidence on post mortem examination were available for study. The spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathy due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). Immunohistochemical analysis of each specimen was conducted using markers of apoptosis, as well as the biochemical apoptotic marker TUNEL. A total of 1800 histopathological slides were analysed. Specimens were also analysed using confocal microscopy to identify the immunopositive cell type. A combination of morphological, immunohistochemical and in situ end-labelling techniques were used to investigate the mechanism of cell death in this experiment. The analytical techniques employed were aimed at showing firstly the presence of apoptosis and secondly the size and position of the damaged regions. RESULTS: Positivity for active Caspase-3, DNA-PKCS, PARP, TUNEL and active Caspase-9 was found in glia (oligodendrocytes and microglia) axons and neurons in both acute and chronic compression above, below and at the site of compression. In chronic compression, the severity of positivity for apoptotic immunological markers was positively correlated with the severity of white matter damage, as measured by APP immunostaining for axonal injury, and Wallerian degeneration. There was no correlation between the duration of chronic compression and immunopositivity for apoptotic markers. In acute SCI, axonal swellings were consistently positive for Caspases −9 and -3, suggesting mitochon-drial activation of apoptotic pathways. CONCLUSION: Apoptosis occurs in both acute and chronic spinal cord injury. In acute compression, axonal injury is associated with apoptotic immunopositivity of glia and neurons. In chronic compression, apoptosis of oligodendrocytes and microglia correlates with demyelination of axons within the white matter

Aims

Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

Aims

Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Aims

To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism.

Aims

Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.

Aims

Various surgical techniques have been described for total hip arthroplasty (THA) in patients with Crowe type III dislocated hips, who have a large acetabular bone defect. The aim of this study was to evaluate the long-term clinical results of patients in whom anatomical reconstruction of the acetabulum was performed using a cemented acetabular component and autologous bone graft from the femoral neck.

Aims

Currently, the US Center for Medicaid and Medicare Services (CMS) has been testing bundled payments for revision total joint arthroplasty (TJA) through the Bundled Payment for Care Improvement (BPCI) programme. Under the BPCI, bundled payments for revision TJAs are defined on the basis of diagnosis-related groups (DRGs). However, these DRG-based bundled payment models may not be adequate to account appropriately for the varying case-complexity seen in revision TJAs.

Aims

Reverse shoulder arthroplasty (RSA) reliably improves shoulder pain and function for a variety of indications. However, the safety and efficacy of RSA in elderly patients is largely unknown. The purpose of this study was to report the mortality, morbidity, complications, reoperations, and outcomes of primary RSA in patients aged > 80 years.

Objectives

The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA).

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.